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.

Effects of Functional Fish Organizations on the Fractal Characteristics of the Microstructure of Feces

Fish feces affect the structure and function of aquatic ecosystems,and they are affected by the functional fish organizations.In this research,Ctenopharyngodon idellus,Hypophthalmichthys molitrix,and Cyprinus carpio were selected to study the effects of different functional fish organizations on the fractal characteristics of fecal micro-structure by scanning electron microscopes(SEM),particles(pores)and cracks analysis system(PCAS).The results showed that fish feces pores mainly consisted of medium pores(cumulative pore number,97%)classified by the International Union of Pure and Applied Chemistry(IUPAC).The grain area fractal dimension D_(1) and the pore-number and pore-size fractal dimension D_(2) were 1.94-1.96 and 2.07-2.19,respectively.The distribution of fish feces pores was very close to the Sierpinski carpet structure,which is the basic fractal construction methods widely used to describe the fractal of pore surface distribution.D_(1)(1.96)and D_(2)(2.19)of Hypophthalmichthys molitrix were the maximum values of the three functional organizations.Combining with the habit of fish,it is inferred that the feces of H.molitrix,the finer the feed and the faster the swimming of fish,the higher the content of feces clay,the larger the fractal dimension of feces,the easier it is to decompose feces,and the high the content of nutrients and organic matter to release into the water.It is demined that fish functional organizations affected the fractal characteristics and the stability of fish feces in water.This study is helpful for further research on water quality prediction and the impact of functional fish organizations on the structure and function of the ecosystem.

Contribution of additives Cu to its accumulation in pig feces: study in Beijing and Fuxin of China

Massive amounts of pig manure are produced by intensive pig farm in China, and the composition of pig manure has changed much due to the use of feed additives. However, little is known about the exact Cu （copper） feed as additives or present as contaminants in pig feed and the residues in feces. One hundred and thirty-seven feeds and one hundred and forty-two fecal samples from 48 pig farms were collected in Beijing and Fuxin cities in 1999 and 2005, respectively. The concentrations of Cu were in the range of 6.86-395.19 mg/kg in the feed samples, and the mean values were in the order of weaner〉 grower-finisher〉 sow＇s feeds. The high concentrations over EU recommendations implied that excessive levels of Cu are fed on many pig farms in Beijing and Fuxin. Cu was also present in high concentrations in feces, and concentrations were highly variable. Cu concentrations in the feces from grower-finisher and weaner pigs were significantly greater than feces of sows. The super-intensive and small-scale farms had higher levels of Cu in feces than the middle farms. Cu concentrations in pig feces were approximately 5-times greater than in pig feeds. Feed management in grower-finisher pigs on super-intensive and small-scale pig farms is needed to reduce high Cu concentrations in feces and risks to soil contamination while feces are land-applied.

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.

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.

Effects of Feces on Spatial Distribution Patterns of Grazed Grassland Communities

Animals excrete feces during grazing. The uneven distribution of feces causes a spatial heterogeneity in grassland communities. In this study, we attempted to clarify the effects of feces on spatial distribution patterns of plant species. A field study was conducted on four grasslands each grazed by a single cow. These four grasslands were defined as Poa pratensis （Kentucky bluegrass） dominated grassland without feces （PoF-）, Poa pratensis dominated grassland with feces （PoF＋）, Zoysia japonica Steud. （Japanese lawngrass） dominated grassland without feces （ZyF-）, and Zoysia japonica Steud. dominated grassland with feces （ZyF＋）. A 50 m line that transects 100 equally spaced quadrats （L-quadrats） was drawn on each of the four grasslands. Each quadrat was 0.50 m × 0.50 m in size and consisted of four equal-area cells of 0.25 m ×0.25 m （S-quadrats）. The occurrences of all plant species were recorded in each S-quadrat. The binomial distribution （BD） and beta-binomial distribution （BBD） were used to represent the variation in spatial patterns. The BBD provided a significant description of the frequency distribution of plants per quadrat. A power law was used to calculate the spatial heterogeneity of each species together with the community heterogeneity. The results revealed that the plants on each of the four grasslands were aggregatively distributed. The ZyF＋ exhibited greater spatial heterogeneity than the ZyF-due to the uneven deposition of feces by cows grazing on the grasslands. Additionally we also found that the feces had effect on the heterogeneity inZyF＋ and did not have effect in PoF＋.

Fine-needle aspiration cytology of liver diseases

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CTX-M producing Escherichia coli isolated from cattle feces in Bogor slaughterhouse,Indonesia

Objective: To determine the occurrence of CTX-M producing Escherichia coli(E. coli)from cattle feces in Bogor slaughterhouse, Indonesia.Methods: A total of 220 cattle feces samples were collected from Bogor slaughterhouse from March to April 2015. Presence of extended-spectrum beta-lactamase(ESBL) producing E. coli was detected by disc diffusion test based on the recommendation from Clinical and Laboratory Standards Institute(2014). Bacterial strains which were confirmed as producing ESBLs were further analyzed for the presence of bla genes of the ESBL by PCR.Results: The results showed that CTX-M producing E. coli isolates were detected in 19 samples from 220 samples(8.6%). The b-lactamase genes detected were CTX-M-1(n = 10) and CTX-M-9(n = 9). All of the CTX-M producing E. coli isolates showed multidrug resistance phenotypes to at least four antibiotics. The highest incidence of antibiotics resistance was showed to ampicillin(100.0%), cefotaxime(100.0%), and cefpodoxime(100.0%), followed by streptomycin(84.3%), trimethoprim-sulfamethoxazole(73.7%), erythromycin(52.6%), kanamycin(26.3%), doxycycline(10.5%), and ceftazidime(0.0%).Conclusions: Detection of CTX-M-producing E. coli in cattle feces raises important questions as they can represent a potential risk factor to public health.

PHYTOPLANKTON,ESPECIALLY DIATOMS,IN THE GUT CONTENTS AND FECES OF TWO PLANTIVOROUS CYPRINIDS-SILVER CARP AND BIGHEAD CARP

In order to clarify whether the planktivorous silver carp and bighead carp can collect phytoplanktonas small as Cyclotella(【20μm)in Donghu Lake,studies on phytoplankton in their gut contents and feceswere made in 1990.The fish were cultured in both net cage in Donghu Lake and aquaria with the lakewater.Past the intestine,the average valve diameter of Cyclotella changed little.The average ratio of emptyfrustule of Cyclotella to total Cyclotella in the foregut contents of the fishes were 1.8—1.9 times higherthan that in the lake water,but changed little from foregut to feces.The aquarium experiment showedthat both carps could collect particles as small as 8-10μm, which was obviously narrower than the dis-tance between their gill rakers.Probably,secretion of mucus plays an important role in collecting suchsmall

In advanced gastric cancer:Prognosis and treatment of patients with positive peritoneal cytology

Positive peritoneal cytology in gastric cancer is classified as M1 disease by the 7thEdition of American Joint Committee on Cancer staging system.With the introduction of laparoscopy and peritoneal washing cytology in the staging of gastric cancer a new category of patients has been identified.These are patients with no macroscopic peritoneal metastases but with peritoneal cytology positive(P0C1).Prognosis and treatment of such patientsrepresent a controversial issue.We evaluate the state of the art of staging system in gastric cancer and discusss tandardisation in staging and treatment procedures.There is still a lack of uniformity in the use of laparoscopy with peritoneal cytology in clinical decision making and in the surgical treatment for gastric cancer.Survival of this patient subset remains poor.Multimodal therapies and new therapeutic strategies are required to improve the survival of these patients.

Biomarkers for hepatocellular carcinoma based on body fluids and feces

Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma(HCC).Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis,predicting responses to specific therapies,evaluating prognosis before or after therapy,as well as serving as novel therapeutic targets.Detection and analysis of proteins,metabolites,circulating nucleic acids,circulating tumor cells,and extracellular vesicles in body fluids(e.g.,blood and urine)and gut microbiota(e.g.,in feces)have excellent capabilities to improve different aspects of management of HCC.Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis,treatment,and monitoring responses of HCC to conventional therapies,most of which may improve diagnosis and management of HCC in the future.This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.