Endoscopic and pathological features of neoplastic transformation of gastric hyperplastic polyps:Retrospective study of 4010 cases

BACKGROUND Hyperplastic polyps,which represent 30%-93%of all gastric epithelial polyps,are the second most common type of gastric polyps after fundic gland polyps.They were previously considered to have no risk of neoplastic transformation.Recently,an increasing number of cases of gastric hyperplastic polyps(GHPs)combined with neoplastic changes have been reported;however,the specific mechanism underlying their transformation has not been thoroughly explored.AIM To investigate the clinical,endoscopic,and pathological characteristics of the neoplastic transformation of GHPs and explore the risk factors.METHODS A retrospective analysis was performed on 4010 cases of GHPs diagnosed by gastroscopy and pathological examination at the hospital from 2005 to 2021.In total,3874,119,and 17 cases were in the group without intraepithelial neoplasia(IN),with low-grade IN,and with high-grade IN,respectively.The data analysis examined the association of endoscopic and pathological features with risk factors for neoplastic transformation.Factors with significant differences were entered into univariate logistic regression,followed by multivariate logistic regression analysis.RESULTS Univariate analysis revealed diameter,multiple polyp presence,redness,rough surface,lobulation,erosion,Yamada classification,location,and gastric mucosa were risk factors for neoplastic transformation.Multivariate analysis showed that age>65 years[odds ratio(OR)=1.789;95%confidence interval(CI):1.227-2.609;P=0.003],male sex(OR=1.680;95%CI:1.158-2.438;P=0.006),multiple polyps(OR=1.851;95%CI:1.230-2.784;P=0.003),pedunculated or semi-pedunculated shape(OR=2.722;95%CI:1.689-4.388;P<0.001),and polyp diameter were significantly associated with GHPs that demonstrated neoplastic transformation.Compared with chronic superficial gastritis,autoimmune gastritis,atrophic gastritis,and gastritis with IN were independent risk factors for neoplastic transformation[(OR=2.672;95%CI:1.559-4.579;P<0.001),(OR=1.876;95%CI:1.134-3.103;P=0.014),and(OR=5.299;95%CI:3.173–8.849;P<0.001),respectively].CONCLUSION Male sex,age>65 years,multiple polyps,pedunculated or semi-pedunculated shape,polyp size>1 cm,and specific background gastric mucosa are key indicators for predicting neoplastic transformation of GHPs.

Current considerations for the surgical management of gallbladder adenomas

Gallbladder adenomas are rare lesions(0.5%)associated with potential malignant transformation,particularly with gallbladder adenomas that are≥1 cm in size.Early detection and management are crucial for preventing lethal carcinoma de-velopment.These polyps can often be distinguished from the more often nonneo-plastic cholesterol pseudopolyps(5%-10%),which are benign.Ultrasonography is the first-line tool for initial diagnosis and follow-up when indicated.The question is whether cholecystectomy is always necessary for all adenomas.The manage-ment of gallbladder adenomas is determined according to the size of the tumor,the growth rate of the tumor,the patient’s symptoms and whether risk factors for malignancy are present.Adenomas≥1 cm in size,an age>50 years and a familial history of gallbladder carcinoma are indications for immediate laparoscopic chole-cystectomy.Otherwise,ultrasound follow-up is indicated.For adenomas 6-9 mm in size,the absence of≥2 mm growth at 6 months,one year,and two years,as well as an adenoma sized<5 mm without existing risk factors indicates that no further surveillance is required.However,it would be preferable to individualize the management in doubtful cases.Novel interventional modalities for preserving the gallbladder need further evaluation,especially to determine the long-term outcomes.

No-touch isolation technique in emergency pancreaticoduodenectomy for neoplastic hemorrhage: Two case reports and review of literature

BACKGROUND Emergency pancreaticoduodenectomy(EPD)is a rare event for complex periam-pullary etiology.Increased intraoperative blood loss is correlated with poor post-operative outcomes.CASE SUMMARY Two patients underwent EPD using a no-touch isolation technique,in which all arteries supplying the pancreatic head region were ligated and divided before manipulation of the pancreatic head and duodenum.The operative times were 220 and 239 min,and the blood loss was 70 and 270 g,respectively.The patients were discharged on the 14^(th) and 10^(th) postoperative day,respectively.Thirty-two patients underwent EPD for the treatment of neoplastic bleeding.The mean operative time was 361.6 min,and the mean blood loss was 747.3 g.The comp-lication rate was 37.5%.The in-hospital mortality rate was 9.38%.CONCLUSION The no-touch isolation technique is feasible,safe,and effective for reducing intraoperative blood loss in EPD.

Significance and relationship between Yes-associated protein and survivin expression in gastric carcinoma and precancerous lesions

AIM:To analyze the differences and relevance of Yes-associated protein (YAP) and survivin, and to explore the correlation and signifi cance of their expression in gastric carcinoma and precancerous lesions.METHODS: The PV9000 immunohistochemical method was used to detect the expression of YAP and survivin in 98 cases of normal gastric mucosa, 58 intestinal metaplasia (IM), 32 dysplasia and 98 gastric carcinoma.RESULTS: The positive rates of YAP in dysplasia (37.5%) and gastric carcinoma (48.0%) were significantly higher than that in normal gastric mucosa (13.3%), P<0.01. The positive rates of survivin in IM (53.4%), dysplasia (59.4%) and gastric carcinoma (65.3%) were significantly higher than in normal gastric mucosa (11.2%), P<0.01. Survivin expression gradually increased from 41.7% in well differentiated adenocarcinoma through 58.3% in moderately differentiated adenocarcinoma to 75.6% in poorly differentiated adenocarcinoma, with significant Rank correlation, rk=0.279, P<0.01. The positive rate of survivin in gastric carcinoma of diffused type (74.6%) was significantly higher than that in intestinal type (51.3%), P<0.05. In gastric carcinoma with lymph node metastasis (76.9%), the positive rate of survivin was signifi cantly higher than that in the group without lymph node metastasis (41.2%), P<0.01. In 98 cases of gastric carcinoma, the expression of YAP and of survivin were positively correlated, rk=0.246, P<0.01.CONCLUSION: YAP may play an important role as a carcinogenic factor and may induce survivin expression. Detecting both markers together may help in early diagnosis of gastric carcinoma.

Pre-operative factors that can predict neoplastic polypoid lesions of the gallbladder

AIM:To investigate the preoperative factors that can predict neoplastic polypoid lesions of the gallbladder(PLGs) as well as malignant PLGs.METHODS:A retrospective analysis was conducted on the 210 consecutively enrolled patients who underwent cholecystectomy due to a PLG larger than 10 mm,as was determined by preoperative trans-abdominal ultrasonography or endoscopic ultrasonography.We ana-lyzed the medical,laboratory,radiologic data and the pathologic results.RESULTS:In 210 cases,146 had non-neoplastic polyps(69.5%) and 64 cases were neoplastic polyps(30.5%).An older age(≥ 65 years),the presence of diabetes mellitus(DM) and the size of polyp(≥ 15 mm) were revealed to be independent predictive variables for neoplastic polyps with odd ratios(OR) of 2.27(P = 0.044),2.64(P = 0.021) and 4.94(P < 0.01),respectively.Among the neoplastic PLGs,an older age(≥ 65 years),the presence of DM and polyp size(≥ 15 mm) were associated with malignancy with ORs of 4.97(P = 0.005),6.13(P = 0.001) and 20.55(P < 0.001),respectively.CONCLUSION:Among patients with PLGs larger than 10 mm in size,higher risk groups such as elderly patients more than 65 years old,those with DM or a large polyp size(≥ 15 mm) should be managed by cholecystectomy.

Efficacy, risk factors and complications of endoscopic polypectomy: Ten year experience at a single center

AIM: To examine the efficacy and complications of colonoscopic resection of colorectal polypoid lesions. METHODS: We retrospectively reviewed 1354 polypectomies performed on 1038 patients over a ten- year period. One hundred and sixty of these were performed for large polyps, those measuring ≥ 20 mm. Size, shape, location, histology, the technique of polypectomy used, complications, drugs assumption and associated intestinal or extra intestinal diseases were analyzed. For statistical analysis, the Pearson χ2 test, NPC test and a Binary Logistic Regression were used. RESULTS: The mean patient age was 65.9 ± 12.4 years, with 671 men and 367 women. The mean size of polyps removed was 9.45 ± 9.56 mm while the size of large polyps was 31.5 ± 10.8 mm. There were 388 pedunculated and 966 sessile polyps and the most common location was the sigmoid colon (41.3%). The most frequent histology was tubular adenoma (55.9%) while for the large polyps was villous (92/160 -57.5%). Coexistent malignancy was observed in 28 polyps (2.1%) and of these, 20 were large polyps. There were 17 procedural bleeding (1.3%) and one perforation. The statistical analysis showed that cancer is correlated to polyp size (P < 0.0001); sessile shape (P < 0.0001) and bleeding are correlated to cardiac disease (P = 0.034), tubular adenoma (P = 0.016) and polyp size.CONCLUSION: The endoscopic resection is a simple and safe procedure for removing colon rectal neoplastic lesions and should be considered the treatment of choice for large colorectal polyps. The polyp size is an important risk factor for malignancy and for bleeding.

Contrast-enhanced ultrasonography in peripheral lung consolidations: What's its actual role?

AIM:To evaluate the diagnostic accuracy of contrastenhanced ultrasonography(CEUS)in the differential diagnosis between neoplastic and non-neoplastic peripheral pleuro-pulmonary lesions.METHODS:One hundred patients with pleural or peripheral pulmonary lesions underwent thoracic CEUS.An 8 microliters/mL solution of sulfur hexafluoride microbubbles stabilized by a phospholipid shell(SonoVue)was used as US contrast agent.The clips were stored and independently reviewed by two readers,who recorded the following parameters:presence/absence of arterial enhancement,time to enhancement(TE),extent of enhancement(EE),pattern of enhancement(PE),presence/absence of wash-out,time to wash-out,and extent of wash-out.After the final diagnosis(based on histopathologic findings or follow-up of at least 15 mo)was reached,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),positive likelihood ratio(PLR),negative likelihood ratio(NLR)of each CEUS parameter in the differential diagnosis between neoplastic and nonneoplastic lesions were calculated.Furthermore,an arbitrary score based on the ratio between the PPVs of each CEUS parameter was calculated,to evaluate if some relationship could exist between overall CEUS behaviour and neoplastic or non-neoplastic nature of the lesions.

Alterations in metastatic properties of hepatocellular carcinoma cell following H-ras oncogene transfection

AIM: To demonstrate the relationship between H-ras oncogene and hepatocellular carcinoma (HCC) metastasis. METHODS: Activated H-ras oncogene was transfected into SMMC 7721, a cell line derived from human HCC, by calcium phosphate transfection method. Some metastasis-related parameters were detected in vitro, including adhesion assay, migration assay, expression of collagenase IV(c IV ase) and epidermal growth factor receptor (EGFR). RESULTS: The abilities of H-ras-transfected cell clones in adhesion to laminin (LN) or fibronectin (FN), migration, c IV ase secretion increased markedly, and the expression of EGFR elevated moderately. More importantly, these alterations were consistent positively with the expression of p21, the protein product of H-ras oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC cell in vitro to raise its metastatic potential.

Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

AIM: To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.

Liver cell adenoma with malignant transformation:A case report

A 57-year-old woman was referred to our hospital because of a liver mass detected by computed tomography.She had taken oral contraceptives for only one month at the age of thirty.Physical examination revealed no abnormalities,and laboratory data,including hepatic function tests,were within the normal range,with the exception of elevated levels of those serum proteins induced by the absence of vitamin K or by raised levels of the antagonist (PIVKA)-Ⅱ (3 502 AU/ml). Abdominal ultrasonography revealed a hyperechoic mass measuring 10×10 cm in the left posterior segment of the liver.Because hepatocellular carcinoma could not be completely excluded,this mass was resected.The tumor consisted of sheets of uniform cells with clear cytoplasm, perinuclear eosinophilic granules and round nuclei.These histological findings were consistent with liver cell adenoma. Background hepatic tissue appeared normal.After resection of the tumor,serum PIVKA-Ⅱ fell to within the normal range. An area of hepatocellular carcinoma (HCC) with a mid- trabecular pattern was immunohistochemically found,which was positive for PIVKA-Ⅱ.Sinusoidal endothelial cells were CD34-positive,containing scattered PIVKA-Ⅱ positive cells. This tumor was therefore finally diagnosed as liver cell adenoma with focal malignant transformation to HCC.

Risk of colorectal polyps in patients with sporadic gastric polyps:A case-control study

AIM:To assess the risk of colonic polyps,adenomas and advanced neoplastic lesions(ANL) in patients with sporadic gastric polyps,especially those with fundic gland polyps(FGP).METHODS:Clinical records of patients who had performed an upper and a lower digestive endoscopy between September 2007 and August 2008 were retrospectively analyzed.A case-control study was carried out,calling patients with gastric polyps as 'cases' and patients without gastric polyps as 'controls'.The risk of colonic polyps,adenomas and ANL(villous component ≥ 25%,size ≥ 10 mm,or high grade dysplasia) was assessed [odds ratio(OR) and its corresponding 95%CI].RESULTS:Two hundred and forty seven patients were analyzed:78 with gastric polyps(cases) and 169 without gastric polyps(controls).Among the cases,the majority of gastric polyps were FGP(80%,CI:69-88) and hyperplastic(20%,CI:12-31);25% had colonic polyps(25% hyperplastic and 68% adenomas,from which 45% were ANL).Among the controls,20% had colonic polyps(31% hyperplastic and 63% adenomas,from which 41% were ANL).The patients with sporadic FGP had an OR of 1.56(CI:0.80-3.04) for colonic polyps,an OR of 1.78(CI:0.82-3.84) for colonic adenomas,and an OR of 0.80(CI:0.21-2.98) for ANL.Similar results were found in patients with gastric polyps in general.CONCLUSION:The results of this study did not show more risk of colorectal adenomas or ANL neither in patients with sporadic gastric polyps nor in those with FGP.

Telomere and telomerase in the initial stage of immortalization of esophageal epithelial cell

AIM: To search for the biomarker of cellular immortalization, the telomere length, telomerase activity and its subunits in cultured epithelial cells of human fetal esophagus in the process of immortalization. METHODS: The transgenic cell line of human fetal esophageal epithelium (SHEE) was established with E(6)E(7) genes of human papillomavirus (HPV) type 18 in our laboratory. Morphological phenotype of cultured SHEE cells from the 6th to 30th passages, was examined by phase contrast microscopy, the telomere length was assayed by Southern blot method, and the activity of telomerase was analyzed by telomeric repeat amplification protocol (TRAP). Expressions of subunits of telomerase, hTR and hTERT, were assessed by RT-PCR. DNA content in cell cycle was detected by flow cytometry. The cell apoptosis was examined by electron microscopy (EM) and TUNEL label. RESULTS: SHEE cells from the 6th to 10th passages showed cellular proliferation with a good differentiation. From the 12th to the 16th passages, many senescent and apoptotic cells appeared, and the telomere length sharply shortened from 23kb to 17kb without expression of hTERT and telomerase activity. At the 20th passage, SHEE cells overcame the senescence and apoptosis and restored their proliferative activity with expression of telomerase and hTERT at low levels, but the telomere length shortened continuously to the lowest of 3kb. After the 30th passage cells proliferation was restored by increment of cells at S and G2M phase in the cell cycle and telomerase activity expressed at high levels and with maintenance of telomere length. CONCLUSION: At the early stage of SHEE cells, telomeres are shortened without expression of telomerase and hTERT causing cellular senescence and cell death. From the 20th to the 30th passages, the activation of telomerase and maintenance of telomere length show a progressive process for immortalization of esophageal epithelial cells. The expression of telomerase may constitute a biomarker for detection of immortalization of cells.

Surgical treatment of ulcerative colitis:Ileorectal vs ileal pouch-anal anastomosis

Total proctocolectomy with ileal pouch-anal anastomosis(IPAA) is the current gold standard in the surgical treatment of ulcerative colitis(UC) refractory to medical management. A procedure of significant magnitude carries its own risks including anastomotic failure, pelvic sepsis and a low rate of neoplastic degeneration overtime. Recent studies have shown that total colectomy with ileorectal anastomosis(IRA) has been associated with good long-term functional results in a selected group of UC patients amenable to undergo a strict surveillance for the relatively high risk of cancer in the rectum. This manuscript will review and compare the most recent literature on IRA and IPAA as it pertains to postoperative morbidity and mortality, failure rates, functional outcomes and cancer risk.

Identification of differentially expressed genes in normal mucosa,adenoma and adenocarcinoma of colon by SSH

AIM: To construct subtracted cDNA libraries and further identify differentially expressed genes that are related to the development of colorectal carcinoma(CRC). METHODS: Suppression subtractive hybridization(SSH) was done on cDNAs of normal mucosa, adenoma and adenocarcinoma tissues from the same patient. Three subtracted cDNA libraries were constructed and then hybridized with forward and backward subtracted probes for differential screening. Positive clones from each subtracted cDNA library were selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. RESULTS: By this way, there were about 3-4 X 10(2) clones identified in each subtracted cDNA library, in which about 85% positive clones were differentially screened. Sequencing and BLAST homology search revealed some clones containing sequences of known gene fragments and several possibly novel genes showing few or no sequence homologies with any known sequences in the database. CONCLUSION: All results confirmed the effectiveness and sensitivity of SSH. The differentially expressed genes during the development of CRC can be used to shed light on the pathogenesis of CRC and be useful genetic markers for early diagnosis and therapy.

Risk factors for neoplastic progression in Barrett's esophagus

Barrett's esophagus (BE) confers a significant increased risk for development of esophageal adenocarcinoma (EAC), with the pathogenesis appearing to progress through a "metaplasia-dysplasia-carcinoma" (MDC) sequence. Many of the genetic insults driving this MDC sequence have recently been characterized, providing targets for candidate biomarkers with potential clinical utility to stratify risk in individual patients. Many clinical risk factors have been investigated, and associations with a variety of genetic, specific gastrointestinal and other modifiable factors have been proposed in the literature. This review summarizes the current understanding of the mechanisms involved in neoplastic progression of BE to EAC and critically appraises the relative roles and contributions of these putative risk factors from the published evidence currently available.

Neoplastic pericardial disease: Old and current strategies for diagnosis and management

The prevalence of neoplastic pericardial diseases has changed over time and varies according to diagnostic methods. The diagnostic factor is usually the detection of neoplastic cells within the pericardial fluid or in specimens of pericardium, but the diagnosis may be difficult. Accurate sampling and cytopreparatory techniques, together with ancillary studies, including immunohistochemical tests and neoplastic marker dosage, are essential to obtain a reliable diagnosis. The goals of treatment may be simply to relieve symptoms (cardiac tamponade or dyspnea), to prevent recurrent effusion for a long-term symptomatic benefit, or to treat the local neoplastic disease with the aim of prolonging survival. Immediate relief of symptoms may be obtained with percutaneous drainage or with a surgical approach. For long term prevention of recurrences, various approaches have been proposed: extended drainage, pericardial window (surgical or percutaneous balloon pericardiostomy), sclerosing local therapy, local and/or systemic chemotherapy or radiation therapy (RT) (external or with intrapericardial radionuclides). The outcomes of various therapeutic approaches vary for different tumor types. Lymphoma and leukemias can be successfully treated with systemic chemotherapy; for solid tumors, percutaneous drainage and the use of systemic and/or localsclerosing and antineoplastic therapy seems to offer the best chance of success. The use of "pure" sclerosing agents has been replaced by agents with both sclerosing and antineoplastic activity (bleomycin or thiotepa), which seems to be quite effective in breast cancer, at least when associated with systemic chemotherapy. Local chemotherapy with platinum, mitoxantrone and other agents may lead to good local control of the disease, but the addition of systemic chemotherapy is probably relevant in order to prolong survival. The surgical approach (creation of a pericardial window, even with the mini-invasive method of balloon pericardiostomy) and RT may be useful in recurring effusions or in cases that are refractory to other therapeutic approaches.

Methylation status of c-fms oncogene in HCC and its relationship with clinical pathology

INTRODUCTIONThe mechanism that DNA hypomethylation leads toactivation of oncogene and occurrence of malignantneoplasm is being increasingly recognized byresearchers. Normal DNA methylation playsimportant role in stabilizing the phenotype of cell.DNA methylation status reduction and/or patternalteration are related to activation and abnormallyhigh expression of some oncogenes and cellularmalignancy[1-6]. c-fms oncogene encodes for colonystimulating factor 1 receptor (CSF-1R)[7], c-fms/CSF-1R was highly expressed in hepatocellularcarcinoma (HCC) tissue, but the mechanismremained obscure[8,9].

Effect of 5-Aza-2'-deoxycytidine on the P16 tumor suppressor gene in hepatocellular carcinoma cell line HepG2

INTRODUCTIONHepatocellular carcinoma (HCC) is one of the mostcommon human malignancies worldwide[1,2], and isclosely associated with infection of HBV and HCVand contamination of aflatoxin B1[3-6]. Althoughthe molecular mechanisms of hepatocarcinogenesisremain poorly understood, an increasing number ofgenetic abnormalities have been recognized[7-10],for example, the p16 gene[11,12] the p53gene[13-18], the E-cadherin gene[19], and the c-mycgene[20].

Effects of histone acetylation and DNA methylation on p21^(WAF1)regulation

Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors.

Cloning of differentially expressed genes in human hepatocellular carcinoma and nontumor liver

INTRODUCTIONThe mechanism of hepatocellular carcinoma(HCC)is still unclear,although some genes have been found to play a role in the transformation of liver cells,and a variety of studies have described differences in gene expression which distinguished tumor from nontumor[1-6].The new genes,especially the functional genes directly related with tumor are still worth being found.The purpose of our study is to find the different genes between human liver tumor and normal tissues using suppression subtractive hybridization.