Ionic liquid-based transparent membrane-coupled human lung epithelium-on-a-chip demonstrating PM0.5 pollution effect under breathing mechanostress

The plausibility of human exposure to particulate matter(PM)has witnessed an increase within the last several years.PM of different sizes has been discovered in the atmosphere given the role of dust transport in weather and climate composition.As a regulator,the lung epithelium orchestrates the innate response to local damage.Herein,we developed a lung epithelium-ona-chip platform consisting of easily moldable polydimethylsiloxane layers along with a thin,flexible,and transparent ionic liquid-based poly(hydroxyethyl)methacrylate gel membrane.The epithelium was formed through the culture of human lung epithelial cells(Calu-3)on this membrane.The mechanical stress at the air–liquid interface during inhalation/exhalation was recapitulated using an Arduino-based servo motor system,which applied a uniaxial tensile strength from the two sides of the chip with 10%strain and a frequency of 0.2 Hz.Subsequently,the administration of silica nanoparticles(PM0.5)with an average size of 463 nm to the on-chip platform under static,dynamic,and dynamic+mechanical stress(DMS)conditions demonstrated the effect of environmental pollutants on lung epithelium.The viability and release of lactate dehydrogenase were determined along with proinflammatory response through the quantification of tumor necrosis factor-α,which indicated alterations in the epithelium.

Genomic characterization of peritoneal lavage cytology-positive gastric cancer

Objective: Positive peritoneal lavege cytology(CY1) gastric cancer is featured by dismal prognosis, with high risks of peritoneal metastasis. However, there is a lack of evidence on pathogenic mechanism and signature of CY1and there is a continuous debate on CY1 therapy. Therefore, exploring the mechanism of CY1 is crucial for treatment strategies and targets for CY1 gastric cancer.Methods: In order to figure out specific driver genes and marker genes of CY1 gastric cancer, and ultimately offer clues for potential marker and risk assessment of CY1, 17 cytology-positive gastric cancer patients and 31matched cytology-negative gastric cancer patients were enrolled in this study. The enrollment criteria were based on the results of diagnostic laparoscopy staging and cytology inspection of exfoliated cells. Whole exome sequencing was then performed on tumor samples to evaluate genomic characterization of cytology-positive gastric cancer.Results: Least absolute shrinkage and selection operator(LASSO) algorithm identified 43 cytology-positive marker genes, while Mut Sig CV identified 42 cytology-positive specific driver genes. CD3G and CDKL2 were both driver and marker genes of CY1. Regarding mutational signatures, driver gene mutation and tumor subclone architecture, no significant differences were observed between CY1 and negative peritoneal lavege cytology(CY0).Conclusions: There might not be distinct differences between CY1 and CY0, and CY1 might represent the progression of CY0 gastric cancer rather than constituting an independent subtype. This genomic analysis will thus provide key molecular insights into CY1, which may have a direct effect on treatment recommendations for CY1and CY0 patients, and provides opportunities for genome-guided clinical trials and drug development.

Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives

BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.

Comparison of smear cytology with liquid-based cytology in pancreatic lesions: A systematic review and meta-analysis

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)is a safe and accurate technique to confirm the diagnosis of pancreatic cancers.Recently,numerous studies comparing the diagnostic efficacy of smear cytology(SC)and liquid-based cytology(LBC)for pancreatic lesions yielded mixed results.AIM To compare and identify the better cytology method for EUS-FNA in pancreatic lesions.METHODS A comprehensive search of PubMed,Embase,and Cochrane was undertaken through July 18,2020.The primary endpoint was diagnostic accuracy(sensitivity and specificity).Secondary outcomes included sample adequacy and post procedure complications.In addition,factors affecting diagnostic efficacy were discussed.RESULTS Data on a total of 1121 comparisons from 10 studies met the inclusion criteria.Pooled rates of sensitivity for SC and LBC were 78%(67%-87%)vs 75%(67%-81%),respectively.In any case,both SC and LBC exhibited a high specificity close to 100%.Inadequate samples more often appeared in LBC compared with SC.However,the LBC samples exhibited a better visual field than SC.Very few post procedure complications were observed.CONCLUSION Our data suggested that for EUS-FNA in pancreatic lesions(particularly solid lesions),SC with Rapid On-Site Evaluation represents a superior diagnostic technique.If Rapid On-Site Evaluation is unavailable,LBC may replace smears.The diagnostic accuracy of LBC depends on different LBC techniques.

Diagnostic value of liquid-based cytology and smear cytology in pancreatic endoscopic ultrasound-guided fine needle aspiration: A meta-analysis

BACKGROUND Smear cytology(SC)using endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)is the established and traditional choice for diagnosing pancreatic lesions.Liquid-based cytology(LBC)is a novel alternative cytological method,however,the comparative diagnostic efficacy of LBC remains inconclusive.AIM To examine the diagnostic efficacy of LBC and SC for pancreatic specimens obtained through EUS-FNA via a systematic review and meta-analysis.METHODS A systematic literature search was performed using PubMed,EMBASE,the Cochrane Library,and Web of Science.The numbers of true positives,false positives,true negatives,and false negatives for each cytological test(LBC and CS)were extracted from the included studies.The pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve(AUC)were calculated,and the AUC was compared by Tukey's multiple comparisons test.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies II tool.RESULTS A total of 1656 patients in eight studies were included.The pooled sensitivity and specificity and the AUC for LBC were 0.76(95%CI:0.72-0.79),1.00(95%CI:0.98-1.00),and 0.9174,respectively,for diagnosing pancreatic lesions.The pooled estimates for SC were as follows:Sensitivity,0.68(95%CI:0.64-0.71);specificity,0.99(95%CI:0.96-100.00);and AUC,0.9714.Similarly,the corresponding values for LBC combined with SC were 0.87(95%CI:0.84-0.90),0.99(95%CI:0.96-1.00),and 0.9894.Tukey’s multiple comparisons test was used to compare the sensitivities and AUCs of the three diagnostic methods;statistically significant differences were found between the three methods,and LBC combined with SC was superior to both LBC(P<0.05)and SC(P<0.05).The pooled sensitivity and AUC did not change significantly in the sensitivity analysis.CONCLUSION LBC may be sensitive than SC in the cytological diagnosis of pancreatic lesions,however,the superior diagnostic performance of their combination emphasizes their integrated usage in the clinical evaluation of pancreatic lesions.

Comparative Study of Cell Findings by Conventional Smear and Liquid-Based Cytology for Oral Exfoliative Cytology

Background: Liquid-based cytology (LBC) is a method of manufacturing cyto-diagnostic specimens. Improved accuracy is expected from standardizing specimen production and use of this method is rapidly spreading in oral cytology. On the other hand, LBC reportedly requires training to show peculiar cell findings compared to those of conventional smear cytology (CVC). Few studies have compared detailed cell findings for oral CVC and LBC. Objectives: The aim of this study was to compare cytological findings between CVC and LBC using cytomorphological image analysis. Materials and Methods: Cytological specimens were collected from 20 patients (negative for squamous neoplasia in 10, dysplasia in 5, squamous cell carcinoma in 5) and 5 controls of the tongue between January 2017 and December 2018. Two different preparation techniques were investigated cytomorphologically for CVC and LBC (BD CytorichTM). Results: LBC showed significantly higher cell numbers than CVC for all lesions. LBC-to-CVC ratio ranged from 9.52 (hyperkeratosis) to 1.87 (deep cells in oral squamous cell carcinoma (OSCC)). Nuclear area of normal, hyperkeratosis, and inflammation were significantly higher in LBC than those of CVC. Hyperchromasia was significantly more frequent with CVC than with LBC for hyperkeratosis, inflammation, dysplasia and OSCC. There was no significant difference in circularity between CVC and LBC among all lesions. Conclusion: Only one cytomorphological disadvantage was seen with LBC, in the form of decreased hyperchromasia. Further clarification of the advantages and disadvantages of LBC is needed, including management of precision and screening practices.

Clinical evaluation of HPV DNA test combined with liquid-based cytology in the diagnosis of cervical disease

Objectives: To evaluate the sensitivity and accuracy of the HPV DNA test in conjunction with thin prep cytology test as a screening method of human papillomavirus (HPV) infection. To study either the cervical erosion is related to high risk HPV infection or to determine the mean age distribution that is more prone to HPV infection. Material and Methods: The study is a retrospective cohort implemented to determine the real performance of liquid based medium and HPV DNA testing combined in second clinical hospital of Jilin University Changchun, China. The study group included total 150 patients from January 1, 2011 to December 30, 2012. A computerized search identified patients with thin prep test results and high risk HPV DNA testing during a 2-year period was recruited. The patients were chosen after proper speculum examination followed by thin prep cytology (TCT) and HPV DNA test. Cytologic specimens were obtained with endocervical brush, which was rinsed into the vial of Cytyc. The residual samples after the cytology report were taken for reflex HPV DNA test. The manufacture protocol was followed for HPV DNA testing using Hybrid Capture II. Colposcopic biopsy was performed for the diagnosis purpose, in patients who had atypical squamous cells of undeter-mined significance (AUS-US), low grade intraepithelial lesion (LSIL) or high-grade intraepithelial lesion (HSIL) in cytology and with positive results of highrisk HPV DNA. The diagnostic criteria were based on the Bethesda System (TBS). Findings: The high risk HPV positive women with abnormal cytology had a CIN I risk of 73 (86%), whereas 35 (23.3%) high-risk HPV positive women out of 109 (72.7%) normal cytology who underwent histological biopsy had CIN I 16 (10.7%). The risk for cervical intraepithelial neoplasia (CIN) in women with high-risk HPV positive with normal cytology was higher among women invited for the first time 31 - 40 years of age 12 (8%) than among older women 1 (0.7%). Out of 44 (29.3%) women who had I degree erosion with 6 (14%) positive HPV DNA test 38 (86%) had a normal histology biopsy showing no statically significant between them. Conclusion: The data confirm that HR-HPV DNA testing is much more sensitive than cytology alone and that HPV DNA testing helps in identifying women with high risk of serious cervical disease in an efficient and medically acceptable manner. The other most significant advantage of this cervical cancer screening method is that women who are HPV DNA positive can easily and quickly referred for colposcopic examination (within one year), which could identify the precancerous and cancer stage. And those who are HPV DNA negative can safely have much longer screening intervals saving considerable costs. With mean age being 38 ± 10 years, age older than 30 years should undergo HPV DNA testing with cytology triage in primary screening. But in woman younger than 30 years using HPV DNA assay, as an initial screening step can increase the prevalence of abnormal smears and the positive predictive value of HPV followed by TCT. However, close follow-up is essential if the initial biopsy is negative because a considerable number of women may have HPV infection positive in subsequent studies.

Vaginal Intraepithelial Neoplasia Detected with Cervical Liquid-Based Cytology: Old Concerns or New Facilities?

Background: The detection of vaginal intraepithelial neoplasia (VAIN) in cervical samples is not a common finding. Therefore, we aimed to report VAINs detected in liquid-based cytology (LBC) from women examined at Hospital das Clínicas of Faculty of Medicine, Sao Paulo State University. Materials and Methods: We evaluated LBC samples from women referred to gynecology examination for different reasons (previous abnormal PapTest, follow up of treated cervical lesion, ecc) and women examined for regular screening proposals, and compared with biopsy diagnoses, including the controversial diagnoses of vaginal intraepithelial neoplasia (VAIN). Results: From 1866 patients, 1423 (76.3%) cases were negative and 443 (23.7%) were positive for any cellular alteration. Age of patients ranged from 12 to 86 years. We detected 25 histologically confirmed VAIN (1.3% p = 0.0002 by Fisher’s exact test IC 95% 0.0090 - 0.0198) and 1.1% VAIN (p = 0.0031 by Fisher’s exact test IC 95% 0.0077 - 0.0179). Conclusion: The identification of VAIN in routine is feasible;the professionals involved with cytological examination should be aware of these lesions in Pap test samples.

Application Analysis of High Risk HPV Detection Combined with Cervical Cytology, Colposcopy and Pathology in Cervical Lesions of Women in Tiandeng County

Purpose: To understand the application of high-risk HPV detection combined with cervical cytology, colposcopy and pathology in cervical lesions of women in Tiandeng County. Method: Women in the outpatient and inpatient departments of our hospital from January 2021 to October 2022 were collected for high-risk HPV testing, TCT, colposcopy and pathological examination according to their personal wishes, to understand the application of relevant examinations in cervical lesions. Result: In 2021, the number of patients was 5801, among whom 1743 patients had received cervical cancer examination in the past, accounting for 30.05% of the total number of patients, and 5795 who had volunteered for TCT examination this time, accounting for 99.90% of the total;A total of 289 cases of atypical squamous cells with unclear significance (ASC-US) were detected, excluding 11 cases of high-grade squamous intraepithelial lesions (ASC-H), 122 cases of low-grade squamous intraepithelial lesions (LSIL), 16 cases of high-grade squamous intraepithelial lesions (HSIL), 2 cases of squamous cell carcinoma (SCC), and 4 cases of atypical adenocyte (AGC);Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of people who volunteered for high-risk HPV testing was 4237, and the number of positive cases was 740, accounting for 17.47% of the screening population;Among 740 HPV-positive patients, 488 high-risk HPV-positive patients were selected for TCT examination, and 87 patients were found to be TCT positive;From 401 high-risk HPV-positive and TCT negative patients, 287 patients with possible lesions were screened out for colposcopy;The results showed that 60 patients may have certain cervical lesions and need further pathological examination and the results showed that 28 patients had CTN1 and 18 patients had CIN2 - 3. In 2022, 8840 patients received medical treatment, among which 3188 patients had received cervical cancer examination in the past, accounting for 36.06% of the total number of patients, and 8314 patients voluntarily underwent TCT examination, accounting for 94.05% of the total number of patients. 434 cases of atypical squamous cells with ambiguous meaning (ASC-US) were detected, excluding 13 cases of high-grade squamous intraepithelial lesions (ASC-H), 217 cases of low-grade squamous intraepithelial lesions (LSIL), 35 cases of high-grade squamous intraepithelial lesions (HSIL), 1 case of squamous cell carcinoma, and 4 cases of atypical adenocarcinoma (AGC);Atypical cervical adenocytosis and cervical carcinoma in situ were not detected. The number of volunteers for high-risk HPV testing was 3871 cases, and the number of positive cases was 654 cases, accounting for 16.89% of the screening number. 527 high-risk HPV-positive patients were selected from 654 HPV-positive patients for TCT examination, and the number of TCT-positive patients was found to be 49. From 478 high-risk HPV-positive patients with TCT negative, 276 patients with possible lesions were screened out for colposcopy;The results showed that 66 patients may have certain cervical lesions and need further pathological examination;and then the results showed that 31 cases of CTN1 and 6 cases of CIN2 - 3. Conclusion: Gynecological high-risk HPV examination can provide better etiological sources for cervical cancer screening;Cervical cytology examination has high sensitivity;Colposcopy examination has high specificity;Pathological examination can be used as an effective supplement for cervical cytology examination and colposcopy;So high-risk HPV combined with cytology examination, colposcopy examination and pathological examination has high clinical application value;It is worth popularizing and applying.

Comparison of brush and basket cytology in differential diagnosis of bile duct stricture at endoscopic retrograde cholangiopancreatography

BACKGROUND： A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreato- graphy （ERCP）. This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD： The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS： We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 （14.9%） and 107 patients （93.9%）, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively （P=0.347 and 0.827 for sensitivity and accuracy, respectively）. The good and excellent cellular yields （≥grade 2） were obtained by Geenen brush and Dormia basket cytology in 88 （77.2%） and 79 （69.3%） patients, respectively.CONCLUSION： The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.

Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Diagnosis of pancreatic cancer by cytology and telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopy

BACKGROUND: Telomerase activity is reported to be specific and frequent in human pancreatic cancer. We conducted this study to assess the usefulness of monitoring telomerase activity in exfoliated cells obtained by pancreatic duct brushing during endoscopic retrograde cholangiopancreatography (ERCP) for the diagnosis of pancreatic cancer. METHODS: Exfoliated cells obtained by pancreatic duct brushing during ERCP from 21 patients (18 with pancreatic cancer, 3 with chronic pancreatitis) were examined. Telomerase activity was detected by polymerase chain reaction and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA). RESULTS: D450 values of telomerase activity were 0.446 +/- 0.2700 in pancreatic cancer and 0.041 +/- 0.0111 in chronic pancreatitis. 77.8% (14/18) of patients with pancreatic cancer had cells with telomerase activity. None of the samples from patients with chronic pancreatitis showed telomerase activity, when the cutoff value of telomerase activity was set at 2.0. Cytological examination showed cancer cells in 66.7% (12/18) of the patients. CONCLUSIONS: Telomerase activity may be an early malignant event in pancreatic cancer development. Cytology and telomerase activity in cells obtained by pancreatic duct brushing may complement each other for the diagnosis of pancreatic cancer.

Endoscopic ultrasound-guided fine-needle aspiration cytology in pancreaticobiliary carcinomas:diagnostic efficacy of cell-block immunocyto-chemistry

BACKGROUND： Endoscopic ultrasound-guided fine-needle aspiration cytology was demonstrated to be a useful tool for the diagnosis and staging of pancreaticobiliary neoplastic le- sions. Nonetheless, the diagnostic value of this procedure may be limited by low cellularity of the specimen, contamination of intestinal cells and unfeasibility of ancillary immunocy- tochemical procedures. The present study was to evaluate its usefulness in the diagnosis of neoplastic lesions.

Research of cervical cytology screening in diagnosis of 370,000 cases with cervical lesion in Guangdong

Objective： Analysis of the results of 37 million cases by using cervical liquid-based cytology screening, discussion the situation of cervical cancer and precancerous lesions in Guangdong province. Methods： From 2002 to 2006, using liquid-based thin-layer cytology （TCT） method screening cervical lesions within 371,929 women in Guangdong. Cytological diagnosis adopt TBS （the Bethesda system） Standard （TBS improved 2001 version of the diagnostic criteria）, statistic positive rate by age and region respectively. Results： 371,929 cases of gynecology cervical samples in Guangdong, 331,251 cases were negative, accounted for 91.23%; cytology positive cases： 32,548 cases were squamous intraepithelial lesions （8.96%）, 486 cases were glandular epithelial lesions （0.13%）; grouped according to age： 30 to 40-year-old positive rate was 9.13%, 40 to 50-year-old positive rate was 9.60%, the latter had higher cytology positive rate; grouped according to region： the total samples in PRD areas were 304.951 cases, accounted for 81.99%, in which 24301 cases were positive （8.14%）, in 66978 cases （18.01%） of NON-PRD regions, 7645 cases were positive （11.87%）, there were 1858 cases had biopsy/follow-up results from 2004 to 2005, and the rate was 2.88%. Conclusion： The cytological positive rate of cervical cancer and its precancerous lesions was 9.09% in Guangdong （of which the rate of cytological diagnosis as precancerous lesions was 3.40%）, 30 to 50 age group had the high incidence of cervical cancer and its precursor lesions, and also the main stage of prevention for cervical cancer. Cytology positive rate was 11.87% in economic underdevelopment Non-Pearl River Delta regions, much higher than the Pearl River Delta region.

Endoscopic ultrasound-guided fine-needle aspiration cytology diagnosis of solid pseudopapillary tumor of the pancreas: A case report and literature review

We describe the clinical, imaging and cytopathological features of solid pseudopapillary tumor of the pancreas (SPTP) diagnosed by endoscopic ultrasound- guided (EUS-guided) fine-needle aspiration (FNA). A 17-year-old woman was admitted to our hospital with complaints of an unexplained episodic abdominal pain for 2 mo and a short history of hypertension in the endocrinology clinic. Clinical laboratory examinations revealed polycystic ovary syndrome, splenomegaly and low serum amylase and carcinoembryonic antigen (CEA) levels. Computed tomography (CT) analysis revealed a mass of the pancreatic tail with solid and cystic consistency. EUS confirmed the mass, both in body and tail of the pancreas, with distinct borders, which caused dilation of the peripheral part of the pancreatic duct (major diameter 3.7 mm). The patient underwent EUS-FNA. EUS-FNA cytology specimens consisted of single cells and aggregates of uniform malignant cells, forming microadenoid structures, branching, papillary clusters with delicate fibrovascular cores and nuclear overlapping. Naked capillaries were also seen. The nuclei of malignant cells were round or oval, eccentric with fine granular chromatin, small nucleoli and nuclear grooves in some of them. The malignant cells were periodic acid Schiff (PAS)-Alcian blue (+) and immunocytochemically they were vimentin (+), CA 19.9 (+), synaptophysin (+), chromogranin (-), neuro-specific enolase (-), a1- antitrypsin and a1-antichymotrypsin focal positive. Cytologic findings were strongly suggestive of SPTP. Biopsy confirmed the above cytologic diagnosis. EUS- guided FNA diagnosis of SPTP is accurate. EUS findings,cytomorphologic features and immunostains of cell block help distinguish SPTP from pancreatic endocrine tumors, acinar cell carcinoma and papillary mucinous carcinoma.

Endoscopic transpapillary brush cytology and forceps biopsy in patients with hilar cholangiocarcinoma

AIM: To evaluate the sensitivity of brush cytology and forceps biopsy in a homogeneous patient group with hilar cholangiocarcinoma.METHODS: Brush cytology and forceps biopsy were routinely performed in patients with suspected malignant biliary strictures. Fifty-eight consecutive patients undergoing endoscopic retrograde cholangio-pancreatography (ERCP) including forceps biopsy and brush cytology in patients with hilar cholangiocarcinoma between 1995-2005.RESULTS: Positive results for malignancy were obtained in 24/58 patients (41.4%) by brush cytology and in 31/58 patients (53.4%) by forceps biopsy. The combination of both techniques brush cytology and forceps biopsy resulted only in a minor increase in diagnostic sensitivity to 60.3% (35/58 patients). In 20/58 patients (34.5%), diagnosis were obtained by both positive cytology and positive histology, in 11/58 (19%) by positive histology (negative cytology) and only 4/58 patients (6.9%) were confirmed by positive cytology (negative histology).CONCLUSION: Brush cytology and forceps biopsy have only limited sensitivity for the diagnosis of malignant hilar tumors. In our eyes, additional diagnostic techniques should be evaluated and should become routine in patients with negative cytological and histological findings.

Efficacy of SpyGlass^(TM)-directed biopsy compared to brush cytology in obtaining adequate tissue for diagnosis in patients with biliary strictures

AIM: To evaluate the diagnostic yield(inflammatory activity) and efficiency(size of the biopsy specimen) of SpyGlassTM-guided biopsy vs standard brush cytology in patients with and without primary sclerosing cholangitis(PSC).METHODS: At the University Medical Center Mainz, Germany, 35 consecutive patients with unclear biliarylesions(16 patients) or long-standing PSC(19 patients) were screened for the study. All patients underwent a physical examination, lab analyses, and abdominal ultrasound. Thirty-one patients with non-PSC strictures or with PSC were scheduled to undergo endoscopic retrograde cholangiography(ERC) and subsequent per-oral cholangioscopy(POC). Standard ERC was initially performed, and any lesions or strictures were localized. POC was performed later during the same session. The Boston Scientific SpyGlass SystemTM(Natick, MA, United States) was used for choledochoscopy. The biliary tree was visualized, and suspected lesions or strictures were biopsied, followed by brush cytology of the same area. The study endpoints(for both techniques) were the degree of inflammation, tissue specimen size, and the patient populations(PSC vs non-PSC). Inflammatory changes were divided into three categories: none, low activity, and high activity. The specimen quantity was rated as low, moderate, or sufficient.RESULTS: SpyGlassTM imaging and brush cytology with material retrieval were performed in 29 of 31(93.5%) patients(23 of the 29 patients were male). The median patient age was 45 years(min, 20 years; max, 76 years). Nineteen patients had known PSC, and 10 showed non-PSC strictures. No procedure-related complications were encountered. However, for both methods, tissues could only be retrieved from 29 pa-tients. In cases of inflammation of the biliary tract, the diagnostic yield of the SpyGlassTM-directed biopsies was greater than that using brush cytology. More tissue material was obtained for the biopsy method than for the brush cytology method(P = 0.021). The biopsies showed significantly more inflammatory characteristics and greater inflammatory activity compared to the cy-tological investigation(P = 0.014). The greater quantity of tissue samples proved useful for both PSC and non-PSC patients.CONCLUSION: SpyGlassTM imaging can be recom-mended for proper inflammatory diagnosis in PSC pa-tients. However, its value in diagnosing dysplasia wasnot addressed in this study and requires further investi-gation.

Conjunctival impression cytology in non-proliferative and proliferative diabetic retinopathy

AIMTo examine the integrity of the ocular surfaces of subjects with and without diabetes with no conjunctival and dry eye signs and symptoms and compare conjunctival impression cytology findings in diabetics with non-proliferative and proliferative diabetic retinopathy.

An elevated preoperative serum calcium level is a significant predictor for positive peritoneal cytology in endometrial carcinoma

Objective:To evaluate preoperative serum calcium concentration and investigate the association between calcium level and positive peritoneal cytology in endometrial carcinoma(EC).Methods:A total of 510 patients who were diagnosed with EC and had surgery were initially enrolled in this study at Peking University People's Hospital between January 2012 and December 2016.Clinical characteristics and preoperative serum calcium,albumin,carbohydrate antigen(CA)125,CA19-9,carcinoembryonic antigen(CEA)were extracted from patient records and evaluated according to postoperative peritoneal cytology.Predictive factors were assessed with Cox univariate and multivariate analyses.Factors selected from multivariate analysis results were used to build a predictive model.Results:A total of 510 patients are identified in our database and 444 patients who fulfilled inclusion and exclusion criteria are included in this study.Univariate analysis revealed that ionized calcium concentration was closely related to positive peritoneal cytology,tumor grade and lymph-vascular space invasion(LVSI).Moreover,peritoneal cytology was significantly associated with hypertension,tubal ligation,serum CA125,CA19-9,CEA and ionized calcium level.Multivariate analysis revealed that albumin-adjusted calcium level,CA125 and tubal ligation were independent predictive factors of positive peritoneal cytology(P<0.05).A combination of ionized calcium level with the other two indexes yielded significantly great area under the curve(AUC=0.824).Conclusions:This study enhanced the value of preoperative ionized calcium level.We also identified several potential biomarkers to predict positive peritoneal cytology in EC patients before surgery.