Gender disparities and woman-specific trends in Barrett’s esophagus in the United States:An 11-year nationwide populationbased study

BACKGROUND Barrett's esophagus(BE)is a known premalignant precursor to esophageal adenocarcinoma(EAC).The prevalence rates continue to rise in the United States,but many patients who are at risk of EAC are not screened.Current practice guidelines include male gender as a predisposing factor for BE and EAC.The population-based clinical evidence regarding female gender remains limited.AIM To study comparative trends of gender disparities in patients with BE in the United States.METHODS A nationwide retrospective study was conducted using the 2009-2019 National Inpatient Sample(NIS)database.Patients with a primary or secondary diagnosis code of BE were identified.The major outcome of interest was determining the gender disparities in patients with BE.Trend analysis for respective outcomes for females was also reported to ascertain any time-based shifts.RESULTS We identified 1204190 patients with BE for the study period.Among the included patients,717439(59.6%)were men and 486751(40.4%)were women.The mean age was higher in women than in men(67.1±0.4 vs 66.6±0.3 years,P<0.001).The rate of BE per 100000 total NIS hospitalizations for males increased from 144.6 in 2009 to 213.4 in 2019(P<0.001).The rate for females increased from 96.8 in 2009 to 148.7 in 2019(P<0.001).There was a higher frequency of obesity among women compared to men(17.4%vs 12.6%,P<0.001).Obesity prevalence among females increased from 12.3%in 2009 to 21.9%in 2019(P<0.001).A lower prevalence of smoking was noted in women than in men(20.8%vs 35.7%,P<0.001).However,trend analysis showed an increasing prevalence of smoking among women,from 12.9%in 2009 to 30.7%in 2019(P<0.001).Additionally,there was a lower prevalence of alcohol abuse,Helicobacter pylori(H.pylori),and diabetes mellitus among females than males(P<0.001).Trend analysis showed an increasing prevalence of alcohol use disorder and a decreasing prevalence of H.pylori and diabetes mellitus among women(P<0.001).CONCLUSION The prevalence of BE among women has steadily increased from 2009 to 2019.The existing knowledge concerning BE development has historically focused on men,but our findings show that the risk in women is not insignificant.

Exercise benefits meet the esophagus

Gastroesophageal reflux disease(GERD)is defined by recurrent and troublesome heartburn and effortless regurgitation or by the specific complications of this condition—that is,esophagitis,esophageal peptic strictures,and Barrett esophagus.1Although GERD is caused by gastric contents'reaching the esophagus,gastric juices can also reach other anatomical locations(pharynx,mouth,larynx,and airways),leading to(or worsening)extra-esophageal conditions(notably asthma)or symptoms(e.g.,wheezing,cough).1 Together with obesity,GERD is the main risk factor for gastroesophageal malignancies.

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Large isolated fibrous tumors in the upper esophagus: A case report

BACKGROUND Solitary fibrous tumors(SFT)are rare spindle cell tumors that are usually benign.A total of 10 cases of SFTs in the upper esophagus have ever been reported.Here,we report the anesthetic management of a patient with a large isolated fibrous tumor of the upper esophagus compressing the tracheal membrane.We also provide a literature review of the current research.CASE SUMMARY We report the case of a 49 year old male with“cough aggravation and wheezing after exercise”,who underwent esophagectomy for a large isolated fibrous tumor compressing the tracheal membrane in the upper esophagus.We advise the use of a single-lumen tube with a blocker in patients with difficult airways to reduce the incidence of airway injury and fibrinoscopy at all stages of the perioperative period to guide airway management.This case study is the first report of the anesthetic management of a large,isolated fibrous tumor compressing the tracheal membrane in the upper esophagus.CONCLUSION This rare case emphasizes the importance of perioperative management of anesthesia in patients with large isolated fibrous tumors of the upper esophagus that compress the tracheal membrane.The use of blocker reduce the incidence of airway injury and fibrinoscopy at the perioperative period to guide airway mana-gement.

Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.

Hybrid argon plasma coagulation for the treatment of Barrett’s esophagus:A prospective,multicenter study

BACKGROUND The incidence of Barrett’s esophagus(BE)in China is lower compared to the Western populations.Hence,studies conducted in the Chinese population has been limited.The current treatment options available for BE treatment includes argon plasma coagulation(APC),radiofrequency ablation and cryoablation,all with varying degrees of success.AIM To determine the efficacy and safety of HybridAPC in the treatment of BE.METHODS The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment.These procedures were performed by seven endoscopists from different tertiary hospitals.The duration of the procedure,curative rate,complications and recurrent rate by 1-year follow-up were recorded.RESULTS Eighty individuals were enrolled for treatment from July 2017 to June 2020,comprising of 39 males and 41 females with a median age of 54 years(range,30 to 83 years).The technical success rate of HybridAPC was 100%and the overall curative rate was 98.15%.No severe complications occurred during the operation.BE cases were classified as short-segment BE and long-segment BE.Patients with short-segment BE were all considered cured without complications.Thirty-six patients completed the one-year follow-up without recurrence.Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment.The mean duration of the procedure was 10.94±6.52 min.CONCLUSION Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up,especially in cases of short-segment BE.This technique could be considered as a feasible alternative ablation therapy for BE.

Robotic Surgery: An Effective Treatment Option for Epiphrenic Diverticulum Associated with Nutcracker Esophagus

Background: Epiphrenic Diverticulum is frequently associated with esophageal motility disorders, such as nutcrackers esophagus. The diagnosis is usually made using imaging studies such as a Barium esophagogram, and esophageal manometry. Surgical treatment options for epiphrenic diverticulum and EN include diverticulectomy and wide myotomy. Aim: The resection of three epiphrenic diverticula and extensive myotomy were performed by robotic thoracoscopy uneventfully. Case presentation: A 65-year-old female complaining of dysphagia for solid foods, Chest pain and regurgitation. Esophagogastroduodenoscopy (EDG) with difficulty in advancing the endoscope at 25 cm and demonstrating an ED, no hiatal hernia and normal stomach and duodenum. Barium Esophagogram showed multiple diverticula and tortuosity throughout the esophagus. Conclusion: With robotic surgery, surgeons can perform highly precise operations with enhanced 3D vision and control. Through this cutting-edge approach, the treatment of ED associated with EN can be drastically changed, promising better outcomes for patients.

Pathologic and Clinical Analysis of Carcinosarcoma of Esophagus (20 Cases)

Objective:Carcinosarcoma of esophagus is an infrequent disease. Here, the pathologic data of larger specimens of this disease are reviewed and analyzed for studying its clinical characteristics in order to provide support information for clinical diagnosis. Methods: To review and study the clinical data of 20 patients of esophageal carcinosarcoma. Results: Most of esophageal carcinosarcoma grew like pileus or polypus in esophagus, a few of them were infiltrating. Microscopic examination of the resected specimens indicated that the tumor is composed of sarcomatous element and carcinomatous element (the main element), and the surface of such tumor was covered mostly by carcinoma tissues. The result of biopsy showed that the tumor is squamous cell carcinoma. X-ray examination indicated that there was polypus-like smooth and tidy filling defect in the esophagus of such patient, and its mucous membrane showed “daubing-trace” like characteristics. Conclusion: Carcinosarcoma of esophagus is a tumor of low invasion, which grows mainly in the esophageal lumen. The clinical symptoms of this tumor are different from those of esophagus carcinoma in certain degree. The “daubing-trace” like characteristics is typical of X-ray picture. The results of most endoscopic biopsies demonstrate squamous cell carcinoma or lower differentiation carcinoma, which are difficult for confirmed diagnosis before operation.

Improved specimen adequacy using jumbo biopsy forceps in patients with Barrett's esophagus

AIM:To assess the sampling quality of four different forceps(three large capacity and one jumbo) in patients with Barrett's esophagus.METHODS:This was a prospective,single-blind study.A total of 37 patients with Barrett's esophagus were enrolled.Targeted or random biopsies with all four forceps were obtained from each patient using a diagnostic endoscope during a single endoscopy.The following forceps were tested:A:FB-220 K disposable large capacity;B:BI01-D3-23 reusable large capacity;C:GBF-02-23-180 disposable large capacity;and jumbo:disposable Radial Jaw 4 jumbo.The primary outcome measurement was specimen adequacy,defined as a well-oriented biopsy sample 2 mm or greater with the presence of muscularis mucosa.RESULTS:A total of 436 biopsy samples were analyzed.We found a significantly higher proportion of adequate biopsy samples with jumbo forceps(71%)(P < 0.001 vs forceps A:26%,forceps B:17%,and forceps C:18%).Biopsies with jumbo forceps had the largest diameter(median 2.4 mm)(P < 0.001 vs forceps A:2 mm,forceps B:1.6 mm,and forceps C:2mm).There was a trend for higher diagnostic yield per biopsy with jumbo forceps(forceps A:0.20,forceps B:0.22,forceps C:0.27,and jumbo:0.28).No complications related to specimen sampling were observed with any of the four tested forceps.CONCLUSION:Jumbo biopsy forceps,when used with a diagnostic endoscope,provide more adequate specimens as compared to large-capacity forceps in patients with Barrett's esophagus.

Cardiac mucosa indicates risk for Barrett esophagus

TO THE EDITORWith interest we read the article by Bani-Hani et al enrifled ＂Pathogenesis of columnar-lined esophagus＂, which has been published in the recent issue of World Journal of Gastroenterology. The review profoundly adds to our understanding of columnar-lined esophagus （CLE） and clearly indicates that CLE represents an acquired condition and develops as a consequence of gastroesophageal reflux disease （GERD）. However, it should be pointed out that inclusion of CLE-histopathology helps to define those at risk for dysplastic and malignant transformation. Histopathology characterizes nondysplastic and dyplastic （low-, high grade dysplasia） CLE.

CARCINOMA ARISING IN BARRETT'S ESOPHAGUS (A REPORT OF 51 CASES)

Fifty-one patients with carcinoma arising in Barrett's esophagus were treated surgically from 1971 to 1990. This represented 10.2% of all treated cases with esophageal carcinoma during the same period. The mean age was 63 years. The most common symptom was dysphagia. According to PTNM staging, 18 were stage II,3 stage III and 3 stage IV. All patients were treated bysurgery. The 30-day hospital mortality was 3.98%. Theone, two and five-year survival rates were 45.9%, 25.0%and 13.6%, respectively. The 5-year survival rate wassignificantly greater for patrents with stage II (25.0%)than for parients with stage III + IV (4.s%) (P<0.05) andfor tumor length less than 6 cm (21%) than for tumorlength greater than 6 cm (0). The results indicate that thesurvival rate following resection is closely related to theclinical stage and tumor size.

Incidence and mortality of esophagus cancer in China, 2008-2012

Objective: To analyze the incidence and mortality rates of esophagus cancer in China from 2008 to 2012.Methods: Incident and mortality cases of esophagus cancer were retrieved from the National Central Cancer Registry(NCCR) database collecting from 135 cancer registries in China during 2008-2012. The incidence and mortality rates of esophagus cancer were calculated by area(urban/rural), region(eastern, middle, western), gender and age group(0, 1-4, 5-84 by 5 years and 85+ years). China census in 2000 and Segi’s world population were applied for age-standardized rates. Joinpoint model was used for time-trend analysis.Results: The crude incidence rate of esophagus cancer was 22.57/100,000. The age-standardized incidence rates by China standard population(ASIRC) and by world standard population(ASIRW) were 14.58/100,000 and14.80/100,000, respectively. The crude mortality rate of esophagus cancer was 17.19/100,000. The agestandardized mortality rates by Chinese standard population(ASMRC) and by world standard population(ASMRW) were 10.80/100,000 and 10.86/100,000 respectively. Incidence and mortality rates of esophagus cancer were higher in males than in females and higher in rural areas than in urban areas. The crude incidence rate in middle areas was the highest among all areas, followed by western areas and eastern areas. The age-specific incidence rate of esophagus cancer was relatively low in age groups before 40 years old and then increased after 45 years old. It peaked in the age group of 80-84 years. The patterns of age-specific mortality rates of esophagus cancer were close to those of age-specific incidence rates. The ASIRC of esophagus cancer decreased dramatically by 29.87% between 2003 and 2012, from 14.33/100,000 to 10.05/100,000. The esophagus cancer incidence rate decreased by 3.76% per year(P>0.05). The mortality rate of esophagus cancer decreased annually over the decades from 2003 to 2012 in China(P>0.05). In females, the annual percentage change(APC) of mortality rate was-5.43%[95% confidence intervals(95% CI):-6.50%,-4.30%](P<0.05) and the mortality rate of esophagus cancer in rural females was statistically significant(APC:-3.20%, 95% CI:-4.20%,-2.20%)(P<0.05).Conclusions: The focus of prevention and treatment for esophagus cancer is strengthening primary prevention of esophageal cancer, and promoting esophagus cancer secondary prevention to reduce incidence and mortality rates of esophagus cancer, prolong survival rate of patients and decline the burden of esophagus cancer in China.

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma(EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus(BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux(GER), male sex, older age, central obesity,tobacco smoking, Helicobacter pylori(H. pylori) eradication, and the administration of proton pump inhibitors(PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes,Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type Ⅰ microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type Ⅱ microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.

Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus

Heterotopic gastric mucosa of the proximal esophagus (HGMPE),also referred to as"inlet patch"or"cervical inlet patch",is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%.Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints.Most consider HGMPE as clinically irrelevant entity.The clinical significance of HGMPE is mainly acid related or neoplastic transformation.The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20%to as high as 73.1%.However,most of these symptoms are mild. Clinically significant acid related complications such as bleeding,ulcerations,structure and fistulization have been reported.Although rare,dysplastic changes and malignancies in association with HGMPE have also been reported.Associations with Barrett's esophagus have also been reported but the findings so far have been conflicting.There are still many areas that are unknown or not well understood and these include the natural history of HGMPE,risk factors for complications,role of Helicobacter pylori infection and factors associated with malignant transformations.Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes.Despite the overall low incidence of clinically relevant manifestations reported in the literature,HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance.

MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is be-coming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.

miR-200 family expression is downregulated upon neoplastic progression of Barrett's esophagus

AIM: To investigate miR-200 family expression in Barrett's epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma. METHODS: Real-time reverse transcriptase-polymerase chain reaction was used to measure miR-200, ZEB1 and ZEB2 expression. Ingenuity Pathway Analysis of miR-200 targets was used to predict biological outcomes. RESULTS: Barrett's epithelium expressed lower levels of miR-141 and miR-200c than did gastric and duodenal epithelia (P < 0.001). In silico analysis indicated roles for the miR-200 family in molecular pathways that distinguish Barrett's epithelium from gastric and duodenalepithelia, and which control apoptosis and proliferation. All miR-200 members were downregulated in adenocarcinoma (P < 0.02), and miR-200c expression was also downregulated in non-invasive epithelium adjacent to adenocarcinoma (P < 0.02). The expression of all miR-200 members was lower in Barrett's epithelium derived high-grade dysplastic cell lines than in a cell line derived from benign Barrett's epithelium. We observed signif icant inverse correlations between miR-200 family expression and ZEB1 and ZEB2 expression in Barrett's epithelium and esophageal adenocarcinoma (P < 0.05). CONCLUSION: miR-200 expression might contribute to the anti-apoptotic and proliferative phenotype of Barrett's epithelium and regulate key neoplastic processes in this epithelium.

Factors predicting survival in patients with proximal gastric carcinoma involving the esophagus

AIM： To investigate the clinicopathologic features which predict surgical overall survival in patients with proxima gastric carcinoma involving the esophagus （PGCE）. METHODS： Electronic pathology database established in the Department of Pathology of the Nanjing Drum Tower Hospital was searched for consecutive resection cases of proximal gastric carcinoma over the period from May 2004 through July 2009. Each retrieved pa- thology report was reviewed and the cases with tumors crossing the gastroesophageal junction line were se- lected as PGCE. Each tumor was re-staged, following the guidelines on esophageal adenocarcinoma, accord- ing to the 7th edition of the American Joint Commission on Cancer Staging Manual. All histology slides were studied along with the pathology report for a retrospec- tive analysis of 13 clinicopathologic features, i.e., age, gender, Helicobacter pylori （H. pylon} infection, surgical modality, Siewert type, tumor Bormann＇s type, size, dif- ferentiation, histology type, surgical margin, lympho- vascular and perineural invasion, and pathologic stage in relation to survival after surgical resection. Prognos- tic factors for overall survival were assessed with uni- and multi-variate analyses. RESULTS： Patients＇ mean age was 65 years （range： 47-90 years）. The male： female ratio was 3.3. The 1-, 3- and 5-year overall survival rates were 87%, 61% and 32%, respectively. By univariate analysis, age, male gender, H. pylori, tumor Bormann＇s type, size, histology type, surgical modality, positive surgical margin, lym- phovascular invasion, and pT stage were not predictive for overall survival; in contrast, perineural invasion （P = 0.003）, poor differentiation （P = 0.0003）, 〉 15 to- tal lymph nodes retrieved （P = 0.008）, positive lymph nodes （P = 0.001）, and distant metastasis （P = 0.005） predicted poor post-operative overall survival. Celiac axis nodal metastasis was associated with significantly worse overall survival （P = 0.007）. By multivariate analysis, ≥ 16 positive nodes （P = 0.018）, lymph node ratio 〉 0.2 （P = 0.003）, and overall pathologic stage （P= 0.002） were independent predictors for poor overa survival after resection. CONCLUSION： Patients with PGCE showed worse over- all survival in elderly, high nodal burden and advanced pathologic stage. This cancer may be more accurately staged as gastric, than esophageal, cancer.

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population

AIM: To investigate the relation of human papillomavirus (HPV) and esophageal squamous cell carcinoma (ESCC) in Iranian patients as compared to normal controls. METHODS: Using MY09/MY11 consensus primers, we compared the prevalence of a HPV L1 gene in tumor tissues from 38 ESCC cases and biopsied tissues from 38 endoscopically normal Iranian individuals. We also compared the presence of HPV16 and HPVA18 in the same samples using type-specific E6/E7 primers. RESULTS: Fourteen (36.8%) of the 38 ESCC samples but only 5 (13.2%) of the 38 control samples were positive for the HPV L1 gene (P= 0.02). Five (13.2%) of the ESCC samples but none of the control samples were positive for the HPV16 E6/E7 gene (P= 0.05). Three (7.9%) of the ESCC samples and 5 (13.2%) of the control samples were positive for the HPV18 E6/E7 gene (P= 0.71). CONCLUSION: Our data are consistent with HPV DNA studies conducted in other high-risk areas for ESCC. HPV should be considered as a potential factor contributing to the high incidence of ESCC in Iran and other high-incidence areas of the world.