Histological Confirmation Of Diagnosis Research Articles

BIOM-21. THE EFFECTIVENESS OF CIRCULATING MICRO RNAS DERIVED FROM GLIOBLASTOMA AS A BIOMARKER FOR EARLY DIAGNOSIS AND PROGNOSIS

Abstract BACKGROUND Glioblastoma is the most common primary intracranial malignancy in adults. In cases where biopsy is not feasible due to tumors in inoperable locations including the brainstem, biomarkers such as micro RNA-21 (miR-21) extracted from blood samples could be utilized for diagnostic or prognostic purposes. In this study, we examined the role of miR-21 as a diagnostic factor in patients with glioblastoma. METHODS Inclusion criteria included patients with age greater than 20 years and with histologic confirmation of diagnosis. The blood samples were collected prior to surgery, after surgical resection, after concurrent chemoradiotherapy, and after 3 cycles of adjuvant temozolomide therapy. Using TaqMan assay, we extracted miR-21 from blood samples and compared its level with tumor volume on brain magnetic resonance imaging (MRI) scans. miR-21 levels before and after treatments were compared within each subject. RESULTS Eleven newly diagnosed glioblastoma patients were enrolled in this study, and final analyses were performed for eight patients with complete follow up serum samples. Two patients with stable disease after treatment displayed a decrease in miR-21 levels. Three out of four subjects with increase in miR-21 showed progressive disease on MRI scans. One patient with stable disease and an increased miR-21 level experienced postoperative intracranial hemorrhage and ischemic event. The two patients with unchanged miR-21 levels showed stable disease. CONCLUSION miR-21 levels were associated with progressive disease in glioblastoma patients. miR-21 has potential be utilized as a diagnostic marker in patients with glioblastoma, and further studies are needed to elucidate its role as a prognostic marker.

Rhinocerebral Form of Invasive Mycosis in COVID-19 Patients: Clinical Course, Diagnosis, Treatment Experience

Background. The incidence of invasive mycoses is reported to increase among patients with a history of new coronavirus infection COVID-19. Adhesion and damage of endothelial cells by zygomycetes lead to fungus angioinvasion, release of a large number of fungal proteases, lipases and mycotoxins, as well as vascular thrombosis, subsequent necrosis of tissues.Objectives. Improvement of the diagnosis and treatment for COVID-19 associated invasive mycosis.Methods. Examination and treatment of 143 patients with invasive mycosis of the maxillofacial area in the period from August 2021 to May 2022 at the Maxillofacial Unit of Regional Clinical Hospital of Emergency Medical Care, Krasnodar Krai, Russia. The diagnosis was confi rmed by cytological, culture-based methods, as well as pathomorphological study of surgical specimen. Follow-up monitoring was carried out in 1, 3, 6 months, with repeated CT and MRI investigations. The group under follow-up monitoring included 91 patients. The incidence of signs was determined via descriptive statistics methods in proportion of the total number of observations and expressed as a percentage. Statistika 12.5 and Excel 2010 (Windows 10) were used in the study, the graphical representation of the material was made in the same programs.Results. Manifestation of invasive mycoses of the maxillofacial area occurred during the early convalescent period of coronavirus infection in specialized infectious hospitals or within two weeks after discharge from the hospital. A typical clinical picture includes rhinocerebral zygomycosis with the development of fungal osteomyelitis of the upper jaw, nasal bones, zygomatic bone, ethmoidal labyrinth bones, sphenoid bone, frontal bone. 17 cases (11.9%) had a lethal outcome as a result of disseminated form of fungal infection caused by Mucorales (14 patients), Aspergillus (3 patients) with damage to the brain, lungs, kidneys and fatal massive necrotic lesions of the craniofacial area. An integrated approach embraced early antifungal therapy (Amphotericin B) as well as surgical debridement of the lesions and provided a positive effect in treatment.Conclusion. Invasive fungal infections require prompt diagnosis and early prescription of antifungal therapy (prior to histological confi rmation of diagnosis) to minimize consequences and prevent fatal outcome. Due to the nonspecifi c nature of clinical symptoms and diffi culties of early diagnosis of invasive zygomycosis and aspergillosis, it is necessary to be alert to potential invasive aggressive mycoses in immunocompromised patients who have a history of a new coronavirus infection COVID-19.

Multicenter Evaluation of Multiparametric MRI Clear Cell Likelihood Scores in Solid Indeterminate Small Renal Masses.

Background Solid small renal masses (SRMs) (≤4 cm) represent benign and malignant tumors. Among SRMs, clear cell renal cell carcinoma (ccRCC) is frequently aggressive. When compared with invasive percutaneous biopsies, the objective of the proposed clear cell likelihood score (ccLS) is to classify ccRCC noninvasively by using multiparametric MRI, but it lacks external validation. Purpose To evaluate the performance of and interobserver agreement for ccLS to diagnose ccRCC among solid SRMs. Materials and Methods This retrospective multicenter cross-sectional study included patients with consecutive solid (≥25% approximate volume enhancement) SRMs undergoing multiparametric MRI between December 2012 and December 2019 at five academic medical centers with histologic confirmation of diagnosis. Masses with macroscopic fat were excluded. After a 1.5-hour training session, two abdominal radiologists per center independently rendered a ccLS for 50 masses. The diagnostic performance for ccRCC was calculated using random-effects logistic regression modeling. The distribution of ccRCC by ccLS was tabulated. Interobserver agreement for ccLS was evaluated with the Fleiss κ statistic. Results A total of 241 patients (mean age, 60 years ± 13 [SD]; 174 men) with 250 solid SRMs were evaluated. The mean size was 25 mm ± 8 (range, 10-39 mm). Of the 250 SRMs, 119 (48%) were ccRCC. The sensitivity, specificity, and positive predictive value for the diagnosis of ccRCC when ccLS was 4 or higher were 75% (95% CI: 68, 81), 78% (72, 84), and 76% (69, 81), respectively. The negative predictive value of a ccLS of 2 or lower was 88% (95% CI: 81, 93). The percentages of ccRCC according to the ccLS were 6% (range, 0%-18%), 38% (range, 0%-100%), 32% (range, 60%-83%), 72% (range, 40%-88%), and 81% (range, 73%-100%) for ccLSs of 1-5, respectively. The mean interobserver agreement was moderate (κ = 0.58; 95% CI: 0.42, 0.75). Conclusion The clear cell likelihood score applied to multiparametric MRI had moderate interobserver agreement and differentiated clear cell renal cell carcinoma from other solid renal masses, with a negative predictive value of 88%. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Mileto and Potretzke in this issue.

OMIC-07. FEASIBILITY AND UTILITY OF EPIGENOMIC PROFILING FOR CHILDHOOD CNS TUMORS IN HONG KONG

Genome-wide DNA methylation profiling has emerged as an important diagnostic tool that complements histopathology for CNS tumors in children and adults. Literature describing its application in Asian countries is nonetheless limited. Herein, we report the feasibility and utility of adopting such platform for children diagnosed with CNS tumors in Hong Kong. A multi-institutional cohort (n=94, 97% of Chinese ethnicity) with CNS embryonal or high grade neuroepithelial tumors (HGNET) diagnosed in Hong Kong from 1996–2020 was assembled based on tissue availability. DNA was extracted from FFPE tumor material (median 301ng, range 13-1000ng), bisulfite converted and profiled with the Infinium Methylation EPIC BeadChip kit. Raw data were analyzed on the German Cancer Research Center MNP 2.0 classifier and through unsupervised dimensionality-reduction analysis (t-SNE) referencing a published CNS tumor reference dataset (GSE90496). The radio-histologic diagnosis included medulloblastoma (n=65), ATRT (n=9), pineal parenchymal tumors (n=7), ETMR (n=5), CNS-PNET (n=4) and other embryonal tumors/HGNETs (n=4). Methylation class could be assigned based on results from MNP 2.0 (calibrated score ≥ 0.9) in 62 patients (66%, including 2 clustering with control) and t-SNE in 22 (23%), while no-match was encountered in 10 (11%). Methylation-based analysis allowed confirmation of diagnosis and assignment of molecular subgroup in 64 patients (68%), confirmation of histologic diagnosis alone in 5 (5%) and resulted in revision/reassignment of diagnosis in 13 (14%). Among medulloblastoma samples that were assigned molecular tumor classes (n=57), 8 clustered with WNT-activated medulloblastoma, 13 with SHH-activated medulloblastoma, 10 with Group 3 medulloblastoma, 21 with Group 4 medulloblastoma, and 5 with non-medulloblastoma entities (high-grade gliomas=3, ETMR=1, ATRT=1). In conclusion, epigenomic profiling allowed refinement of disease classification for pediatric CNS tumors. Availability of such methodology in Asia sets the stage for international collaborations in molecularly-driven trials.

Diagnosis of lung cancer: a necropsy-based study of 128 cases (1997-2016).

The diagnosis of lung cancer (LC) may be difficult to make in the elderly. We report on the diagnostic elements available in life in an LC necropsy case series of asbestos-exposed workers and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices. We reviewed pathologic and clinical records of an unselected series of autopsies (1997-2016) in patients with LC employed in the Monfalcone shipyards. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings. Data on 128 autopsy-confirmed LC cases were available; in life, 119 had been diagnosed as LC. Among these, 49 had histologic confirmation of diagnosis (17 with immunophenotyping); histology had been negative in 4. Cytology had been the main positive finding and the basis for diagnosis in 24 cases, but had been negative in 13. Chest computed tomography had been the basis for diagnosis in 45; in 18 cases, it had been negative. Nine patients had received a diagnosis different from LC, among whom 4 had been suspected to have malignant pleural mesothelioma by chest computed tomography. Pleural plaques were found in 124 and histologic asbestosis in 46 cases. Autopsies confirmed all LC diagnoses received in life, including 46 that would have been considered only possible LC based on clinical workup. The overall survival in this case series was poor. The high prevalence of pleural plaques and asbestosis suggest severity of asbestos exposures.

Malignant transformation of tailgut cysts is significantly higher than previously reported: systematic review of cases in the literature.

The best treatment for tailgut cysts has not been firmly established. We report a systematic review of the cases in the available literature in order to provide an evidence base for treatment. A systematic search of articles wholly or partly in English was made of PubMed, Embase and Google Scholar; additional studies were discovered by searching reference lists and contacting authors directly. Search terms 'tailgut cyst', 'tail gut cyst', 'retrorectal hamartoma' and 'retrorectal tumour' were used for case reports or case series; no publication date restrictions were imposed. Only studies with histological confirmation of diagnosis and reporting the age and gender of patients were included. Papers were excluded by consensus between the first two authors. A total of 196 individual cases were analysed in detail including 51 cases of neoplasia. The overall rate of neoplastic transformation was 26.6%. Although the male:female cyst incidence ratio was 1:4, men over 18 had a significantly greater relative risk of neoplasm at 1.94 (P=0.0055). Radiological evidence of nodular thickening of the cyst wall significantly increased the relative risk of the presence of cancer (P=0.0023). Current orthodoxy that these are not dangerous embryological remnants is unfounded and may be false. The available data suggest the risk of malignant transformation is high and will apply to any residual tissue after excision. The same rationale behind total mesorectal excision in rectal cancer applies to tailgut cysts. Consequently they should be resected with similar oncological margins.

On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997-2016).

Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices. We reviewed pathologic and clinical records of an unselected series of autopsies (1977-2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping. Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases. Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.

P3.03-038 Improving Quality of Care and Outcomes for Patients Diagnosed with Pleural Mesothelioma in England: Topic: Mesothelioma Clinical

Mesothelioma data has been collected by the National Lung Cancer Audit (NLCA) since it was introduced in 2004 to improve standards of care for patients in the UK and ultimately improve outcomes. The first mesothelioma-specific report combining data submitted to the audit from 2008-2012 was reported in 2014, capturing approximately 85 per cent of total incident mesothelioma cases. This same year, the NLCA switched from using a bespoke dataset to use the generic Cancer Outcomes and Services Dataset (COSD), linked to other National Cancer Registration and Analysis Service (NCRAS) registry datasets, as its primary data source. This dataset change has allowed data for all mesothelioma cases diagnosed during 2014, in England, to be analyzed for the first time and reported here. Using 2014 COSD data submitted to the NLCA for all hospital trusts in England, we have analyzed demographic, diagnostic and active treatment data items and in particular, have calculated the proportion of cases receiving histological subtype confirmation, palliative chemotherapy and per cent surviving to one year after diagnosis, both nationally and by strategic cancer network (SCN). There were 2179 cases of pleural mesothelioma diagnosed in England in 2014. Histological confirmation of diagnosis was very high, but the proportion of mesothelioma cases without histological sub-classification (M9050/3) was 47%. This unspecified mesothelioma rate varied from 32.6 up to 74.4% by cancer network across England. Overall, palliative chemotherapy was given to 51% of patients with performance status (PS) 0-1, however at network level, this varied from 42.2% up to 77.4%. For all cases of mesothelioma, the 1 year overall survival was 43% with variation by network from 37.5 to 55.6% with adjusted odds ratios (OR) ranging from OR 0.8 up to 1.56. There has been improvement in the proportion of mesothelioma patients in England receiving histological subtyping compared to previous years and in the proportion of patients with good PS being treated with palliative chemotherapy. However, there is still marked variation across the country and addressing this may improve national outcomes further. Cancer networks and individual hospitals should examine their results and implement mechanisms to ensure best practice is being followed.

Incidental radiographic findings of thyroglossal duct cysts: Prevalence and management

Objectives/HypothesisTo determine the epidemiology of incidental thyroglossal duct cysts (TGDC) discovered on imaging studies obtained in the head and neck area in children and to discuss subsequent management. MethodsA retrospective chart review was performed at Texas Children's Hospital of all computed tomography (CT) and magnetic resonance (MR) imaging studies obtained in the head and neck region between July 2011 and July 2014. Images obtained for the purpose of evaluating a neck or lingual mass were excluded from the study, as were patients with previously known TGDCs. Data including age, sex, location of TGDC, size, presence of symptoms, referral to Otolaryngology, and intervention were recorded. ResultsA total of 60,663 CT and MR studies of the head, brain, sinus, neck, and C-spine during this time period were reviewed; of these 69 (0.1%) cases contained incidental discovery of probable TGDCs with more males (40) than females (29). Ages ranged from 3 days to 17 years old, with the mean age at 5 years. Locations varied, with majority at base of tongue (83%) followed by hyoid (13%) then infrahyoid straps (4%). Sizes ranged from 2 to 28 mm with average size at 8 mm. 11 of these patients were referred to an Otolaryngologist; 9 were asymptomatic and decision was made to observe, the other two subsequently underwent surgical excision secondary to mass effect and dysphagia with histologic confirmation of diagnosis. ConclusionTGDCs commonly present as an anterior neck mass, however the majority of incidentally discovered TGDCs on imaging are located at the base of tongue. Management of these findings should include referral to an Otolaryngologist for further evaluation with the decision to intervene surgically based on development of clinical symptoms.

A MicroRNA Panel in Pancreatic Cyst Fluid for the Risk Stratification of Pancreatic Cysts in a Prospective Cohort.

A subset of pancreatic cystic neoplasms are regarded as precursor lesions of pancreatic cancer, but only a minority of all pancreatic cystic neoplasms will undergo malignant transformation. MicroRNAs are increasingly recognized as molecular targets in carcinogenesis. Previously, a 9-microRNA (miR) signature was suggested to discriminate between high risk and low risk pancreatic cystic neoplasm. In this study, we aimed to validate this 9-miR panel in a prospective cohort. Total miR was isolated from pancreatic cyst fluid and expression of miR18a, miR24, miR30a-3p, miR92a, miR99b, miR106b, miR142-3p, miR342-3p, and miR532-3p was analyzed by singleplex Taqman MicroRNA Assay. A total of 62 patient samples were analyzed. During follow-up, 24 (38.7%) patients underwent resection, of which 6 (9.7%) patients showed at least high grade dysplasia. A logistic regression model presented a “predicted risk” score which significantly differed between low and high risk cysts, either including all patients or only those with histological confirmation of diagnosis. Using a set cut-off of 50%, the sensitivity of the model for the total cohort was 10.0%, specificity 100.0%, positive predicted value 100.0%, negative predicted value 85.2%, and diagnostic accuracy of 85.5%. Thus, while observing a significant difference between low and high risk cysts, clinical implementation of this biomarker panel is as yet unlikely to be beneficial in the management of pancreatic cysts.

PTH-107 Geoepidemiology of hepatocellular carcinoma (hcc) in the island of crete. a possible role of pesticides

Introduction Geoepidemiological data of HCC are lacking in Greece. The island of Crete has a genetically homogeneous population with minimal immigration and therefore is suitable for such studies attempting to identify a possible contribution of environmental factors in HCC. Method We used a data base of HCC patients constructed over the past 20 years in our Unit, the reference centre for liver disease in the island. Similar data bases for chronic HCV and HBV were also used. All patients had a histological confirmation of diagnosis. Recorded data included gender, date and place of birth and place of residence for the last 15 years. The geographic area of the study comprised the four prefectures of the island of Crete. Population statistics from 1980–2010 were obtained from the Hellenic Statistical Authority. 316 HCC patients, 633 HCV and 392 HBV patients were included in the study. Time-spatial methods were applied in Gis – ArcMap 10 software. A spatial statistical test that measures spatial autocorrelation (Moran`s index) was applied at a confidence level of 95%, in order to detect any possible significant difference between the spatial distribution to place of residence. Density maps with the spatial clusters configuring the prevalence of the disease of all provinces in the island were created. Kriging Interpolation method was applied, to produce a prediction map of HCC in Crete. Results HCV is present in pockets of high prevalence while HBV is more uniformly distributed. HCC is more prevalent in Eastern Crete. A significant spatial autocorrelation between HCC and either HCV (Moran’ I=0.64, p Conclusion 1) HCC is mostly found in Eastern Crete and is broadly associated with the dispersion of chronic HCV and more so with Chronic HBV. 2) In an area with widespread use of pesticides a higher than expected spatial distribution of HCC was detected. Disclosure of interest None Declared.

Intraocular Neuromuscular Choristoma: A Case Report and Literature Review

Neuromuscular choristomas (NMCs) are rare benign tumors of the peripheral nerves. Although histopathological characteristics of this unusual lesion have been recognized, in this regard, neuroimaging findings have not been well described previously. We report the first intraconally located NMC affecting the oculomotor nerve, with histopathological and radiological characteristics. A 10-year-old girl presented with sudden-onset left temporal and retro-orbital pain. Magnetic resonance imaging scans demonstrated a small, capsulated, retro-orbital, intraconal solid lesion that was diagnosed as an atypical dermoid cyst preoperatively. The tumor was resected subtotally. Postoperatively, the patient became pain free, but ipsilateral ptosis and upward eye movement failure developed. Histologically, the lesion consisted of well-differentiated striated muscle fibers intermingled with mature nerve elements consistent with the NMC. Although intracranial NMCs need histological confirmation for diagnosis, neuroimaging might contribute to the preoperative diagnosis and management strategy of treatment. We report the first intraconal NMC, which should be considered in the differential diagnosis of intraorbital tumors.

Ultrasound scan and magnetic resonance imaging for the diagnosis of adenomyosis: systematic review comparing test accuracy

Adenomyosis is a common condition that causes substantial morbidity. Until recently, the reference standard for a definitive diagnosis was histology of hysterectomy specimens. Ultrasound and magnetic resonance imaging (MRI) may allow accurate non-invasive diagnosis. To compare the diagnostic accuracy of these techniques. Systematic review with meta-analysis. Women who had ultrasound and/or MRI, and whose results were compared with a reference standard. Electronic searches were conducted in literature databases from database inception to 2010. The reference lists of known relevant articles were searched for further articles. Selected studies reported data on ultrasound and/or MRI with histological confirmation of diagnosis. Two reviewers independently selected articles without language restrictions, and extracted data in the form of 2 × 2 tables. We computed sensitivity and specificity for individual studies and pooled these results in a meta-analysis. We also performed meta-regression to examine how the index tests compared on diagnostic accuracy. Twenty-three articles (involving 2,312 women) satisfied the inclusion criteria. Transvaginal ultrasound had a pooled sensitivity of 72% (95% CI 65-79%), specificity of 81% (95% CI 77-85%), positive likelihood ratio of 3.7 (95% CI 2.1-6.4) and negative likelihood ratio of 0.3 (95% CI 0.1-0.5). MRI had a pooled sensitivity of 77% (95% CI 67-85%), specificity of 89% (95% CI 84-92%), positive likelihood ratio of 6.5 (95% CI 4.5-9.3), and negative likelihood ratio of 0.2 (95% CI 0.1-0.4). The results show that a correct diagnosis was obtained more often with MRI. Transvaginal ultrasound and MRI show high levels of accuracy for the non-invasive diagnosis of adenomyosis.

Erlotinib added to carboplatin and paclitaxel as first-line treatment of ovarian cancer: A phase II study based on surgical reassessment

Background The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel improved pathologic complete response (pCR) at reassessment surgery in epithelial ovarian, fallopian tube, or primary peritoneal cancers (OFPC). Methods Patients with stage III–IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or, after histologic confirmation of diagnosis, neoadjuvantly. Treatment included paclitaxel (175 mg/m 2) and carboplatin (AUC 6) every 3 weeks for up to 6 cycles, plus oral erlotinib 150 mg daily. The primary objective was to determine whether the pCR rate at reassessment surgery was at least 60% after optimal cytoreduction at initial surgery (< 1 cm residual disease), or at least 40% after suboptimal cytoreduction (at least 1 cm residual disease) using a two-stage design (alpha = 0.10, beta = 0.10). Results The study population included 56 patients with stage III-IV OFPC. EGFR gene amplification was present in 15% of the 20 tumors evaluated. Twenty-eight patients had protocol therapy after optimal cytoreduction (stratum I), 23 had protocol therapy either after suboptimal cytoreduction (stratum II), and 5 received neoadjuvant therapy prior to cytoreduction (stratum III). Pathologic CR was confirmed in 8 patients (29%; 95% confidence intervals 13%, 49%) in stratum I and 3 patients (11%, 95% C.I. 2%, 28%) in stratum II, which did not meet the prespecified efficacy endpoint in either stratum. Conclusions Among unselected patients, erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III–IV OFPC.

Glycosylation Variants of Mucins and CEACAMs As Candidate Biomarkers for the Diagnosis of Pancreatic Cystic Neoplasms

Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis. We used a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of mucin (MUC)1, MUC5AC, MUC16, carcinoembryonic antigen, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (n=17), intraductal papillary mucinous neoplasms (n=15), serous cystadenomas (n=12), or pseudocysts (n=9), with confirmation of histologic diagnosis at surgical resection. The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (mucinous cystic neoplasms+intraductal papillary mucinous neoplasms) from benign cystic lesions (serous cystadenomas+pseudocysts) with a 78% sensitivity at 80% specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87% at 86% specificity. These biomarkers performed better than cyst fluid carcinoembryonic antigen (37%/80% sensitivity/specificity). These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.

Association between response to primary treatments and MGMT status in glioblastoma

The median overall survival and, more importantly, the 2-year survival rate of patients with newly diagnosed glioblastoma are increased by the administration of combined temozolomide and radiotherapy, which has recently become the new standard of treatment in patients with a histological confirmation of diagnosis. Moreover, the assessment of O6-methylguanine-DNA methyltransferase gene promoter methylation has clarified the impact of this approach, and improved upon the interpretation of doubtful cases after concurrent radiotherapy/ temozolomide treatment. Therefore, future strategies in the treatment of glioblastoma patients will include stratification for MGMT methylation status, and various approaches based on epigenetic features are currently under investigation.

NEUROMUSCULAR CHORISTOMA OF THE OCULOMOTOR NERVE

AbstractOBJECTIVENeuromuscular choristomas (NMC) are rare benign tumors of the peripheral nerves. We report an NMC affecting the oculomotor nerve.CLINICAL PRESENTATIONAn 18-year-old girl presented with long-standing intermittent retro-orbital pain and oculomotor paresis. Magnetic resonance imaging scans demonstrated a small nodular lesion on the left oculomotor nerve, similar to the findings for a schwannoma.INTERVENTIONThe tumor was resected with the parental oculomotor nerve, which was reconstructed using a peroneal nerve graft. Postoperatively, the patient became pain-free, and her oculomotor function partially recovered. Histologically, the lesion consisted of well-differentiated smooth muscle fibers intermingled with mature nerve elements consistent with the diagnosis of an NMC, although the possibility of leiomyoma in this rare location was not excluded completely.CONCLUSIONNMC may need histological confirmation for diagnosis if they occur in the intracranial space. The resection is feasible, and the function of the affected nerve can be at least partially restored with the nerve reconstruction.

Diagnosis of Ostreid herpesvirus 1 in fixed paraffin-embedded archival samples using PCR and in situ hybridisation

In 1994, some of the high mortality episodes that affected oysters cultured in France were associated with herpesviral infections. Through histology analysis, however, viral presence could only be suspected and confirmation of histological diagnosis by transmission electron microscopy was performed in only a few cases. Subsequently, the characterisation and genome sequencing of Ostreid herpesvirus 1 (OsHV-1) made possible the development of specific molecular detection (PCR and in situ hybridisation (ISH)). Using both molecular tools, attempts were made to screen for OsHV-1 a number of fixed, paraffin-embedded oyster samples collected and processed in 1994. The aim was to compare these techniques and to estimate the accuracy of histology-based indication of viral infection. Existing DNA extraction protocols were adapted for oyster samples and two pairs of specific primers targeting small fragments (less than 200 bp) were designed (C 9/C 10 and B 4/B 3). The poor consistency observed between the results of PCR with both primer pairs was confirmed by statistical analysis. C 9/C 10, which targets a repeated region of the OsHV-1 genome, appears to be the primer of choice for viral detection in archival samples. In situ hybridisation may furnish complementary information concerning the localisation of viral foci. Under certain conditions, retrospective examination of archival samples by molecular techniques may therefore provide valuable epidemiological data.

Elevated serum triiodothyronine (t3) in Ashkenazi Jewish prostate cancer patients carrying the i1307k allele of the APC(adenopolyposis coli) gene

Purpose The risk of developing any cancer in carriers of the I1307K mutation of the adenopolyposis coli (APC) gene is significantly increased (odds ratio 1.5, P = 0.01). One of the cancers associated with the I1307K mutation is prostate cancer (odds ratio 2.0, P = 0.14). Also, there is an association of APC mutations with thyroid cancer. In this study, we measured triiodothyronine (t3) levels in Ashkenazi Jewish prostate cancer patients, with and without the I1307K mutation of the APC gene. Materials and methods Participants in our study were found through urology and radiation oncology clinics in 1999 and 2000. All eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. The I1307K allele of the APC gene was detected by amplification of DNA isolated from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Serum t3 level was determined by fluorescent immunoassay with a standard, commercially available instrument. Results We studied 77 patients. The youngest patient was 46, the oldest 88, average age 67 ± 7.2 (mean ± SD). Eleven males carrying the APC I 1307K allele had significantly higher serum t3 levels than 66 males carrying the wild type allele. There were no homozygotes for the I1307K allele. None of the males had a t3 level that was above the normal range for our laboratory (137 ng/dl). Conclusions Our finding of increased serum t3 level with the APC I1307K allele in prostate cancer patients is not surprising, given the mitogenic potential of t3. Further studies may clarify whether t3 elevation is the mechanism whereby APC gene mutations increase the risk of prostate cancer; or whether other pathophysiologic abnormalities are involved.

Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer.

In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA ⩽10, stage ⩽T2a, or Gleason grade ⩽6. Medium risk: 10 <PSA ⩽15, Gleason 7 or stage T2b. High risk: Gleason >7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r2=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r2 =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.British Journal of Cancer (2002) 87, 726–728. doi:10.1038/sj.bjc.6600526 www.bjcancer.com© 2002 Cancer Research UK