Adenocarcinoma in Barrett's esophagus

Adenocarcinoma arising in association with the columnar-lined esophagus is now recognized with increasing frequency. The incidence of malignant degeneration in Barrett's esophagus, its etiology, and pathogenesis are all issues of ongoing debate. The role of gastroesophageal reflux in driving the malignant change remains unproven. Surgical resection is the treatment of choice; however, prognosis is generally poor. Surveillance of patients with non-malignant Barrett's esophagus permits detection of early lesions where resection results in excellent long-term survival.     

Adenocarcinoma of the esophagus: a survival study.

A 35 year review of adenocarcinomas of the esophagus was undertaken. We found the disease to be one of increasing incidence afflicting white males disproportionately. Risk factors remain to be clarified. Radiation therapy in curative doses and complete resection were competitively effective in terms of long-term survival. No survival advantage was found with palliative surgery compared with other means of therapy. Optimal combinations of treatment remain to be discovered.     

Adenocarcinoma arising from ectopic gastric mucosa in the cervical esophagus

Ectopic (heterotopic) gastric mucosa (EGM) of the upper esophagus, referred as inlet patch, is an asymptomatic benign lesion that is often detected during endoscopic examination. Although it is considered a source of adenocarcinoma in the upper esophagus, only 17 cases of adenocarcinoma have been reported previously. We report a rare case of adenocarcinoma arising in EGM of the cervical esophagus.     

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

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Clinicopathological and immunohistochemical study of cancer arising from Barrett's esophagus.

In Japan, Barrett's esophageal cancer is a very rare disease. We examined clinicopathologically and immunohistologically 4 patients with Barrett's esophageal cancer who underwent surgical resection in our department. Barrett's esophageal mucosa was classified into 3 types for detailed observation. Specialized columnar epithelium (SCE) remained on the orifice side of carcinoma, and progression to adenocarcinoma was observed in some dysplastic glands. positive findings were detected on p53 immunohistochemical staining, and the ki-67 labeling index was higher than other types. SCE-type Barrett's esophagus may be a precancerous lesion arising prior to the development of adenocarcinoma.     

Multistage carcinogenesis in Barrett's esophagus

The multistage carcinogenesis of esophageal adenocarcinoma is a process of clonal evolution within Barrett's esophagus neoplasms. The initiating event for Barrett's esophagus is unknown, but is associated with chronic gastric reflux which probably also promotes progression. Inactivation of both alleles of CDKN2A appear to be early events causing clonal expansion. Clones with TP53 inactivated expand if they have already inactivated CDKN2A. After TP53 has been inactivated, tetraploid and aneuploid clones tend to develop. The final events that lead to invasion and metastasis are unknown. Evolutionary biology provides important tools to understand clonal evolution in progression and cancer prevention.     

Adenocarcinoma in Barrett's esophagus following total resection of the gastric remnant: a case report.

We report a case of adenocarcinoma in Barrett's esophagus following a total resection of the gastric remnant. A 52-year-old man had undergone a distal gastrectomy for gastric cancer at 33 years of age and a total resection of the gastric remnant for local recurrence of the gastric cancer at 35 years of age. Repeated endoscopic examinations revealed the sequence of reflux esophagitis and Barrett's esophagus. Furthermore, adenocarcinoma in Barrett's esophagus was detected in December, 1989. A subtotal esophagectomy was performed in January, 1990. The elevated lesion in the lower esophagus showed coarse lobulation and measured 7.4 x 3.2 cm. The histologic type was that of well-differentiated adenocarcinoma, with the invasion limited to the muscularis mucosae without lymph node involvement. Severe dysplasia was seen adjacent to the definite carcinoma. The case supports the acquired theory of pathogenesis for Barrett's esophagus and suggests that reflux esophagitis after total gastrectomy may result in a dysplasia-carcinoma sequence.     

Tumor budding as a useful prognostic marker in T1‐stage squamous cell carcinoma of the esophagus

Background

Establishing a new prognostic factor for early‐stage cancer may seem difficult due to the small number of disease‐specific deaths. Tumor budding has been recognized as a useful microscopic finding reflecting biological activity of the tumor.

Methods

Tumor budding stand for isolated single cancer cells and cell clusters scattered beyond the tumor margin at the invasive front. It was searched for in the resected esophagus with T1 squamous cell carcinoma (SCC), and the correlation between the tumor budding, patient survival, and various pathologic factors were analyzed to verify whether tumor budding is a prognostic factor in superficial esophageal cancer.

Results

Seventy‐nine patients undergoing curative esophagectomy were assigned to frequent (n = 29) and rare (n = 50) groups according to the microscopically observed frequency of tumor budding in the tumor. Three‐year survival rates after esophagectomy were 48.8% for the frequent group and 94.5% for the rare group. Multivariate analysis using the Cox proportional hazards model identified this morphological variable as a significant independent prognostic factor.

Conclusions

Tumor budding reflects the biological activity of the tumor and may be a useful prognostic indicator even in early‐stage SCC of esophagus. J. Surg. Oncol. 2013;108:42–46. © 2013 Wiley Periodicals, Inc.     

Adenocarcinoma arising in vulvar breast tissue

A patient with adenocarcinoma arising in vulvar ectopic breast tissue is described. Hormonal receptors of the tumor are analyzed. This is the first case in which an intensive treatment with combined surgery, radiation, hormonal therapy, and cytotoxic chemotherapy was given. Five cases reported previously in the literature are reviewed.     

137例老年宫颈癌临床特征及预后影响因素探讨

目的:探讨老年宫颈癌患者临床特点及预后影响因素。方法:收集137例老年宫颈癌患者的临床资料,采用单因素分析、Logistic回归分析及Kaplan-Meier法回顾性分析影响老年宫颈癌患者预后的危险因素。结果:患者的年龄、民族、孕次、产次、病理分化程度、肾积水、糖尿病对预后无影响（均P>0.05）。初潮时间、病理类型、FIGO分期、盆腔淋巴结转移、治疗方式对预后有影响（均P<0.05）。单因素分析及Logistic回归分析结果显示治疗方式、FIGO分期、初潮时间为影响患者预后的独立危险因素（均P<0.05）。结论:在老年宫颈癌患者的治疗中,应注意患者FIGO分期晚、单一的治疗方式、初潮时间较早对预后的影响。     

Esophageal adenocarcinoma arising in Barrett esophagus

The major risk factors for esophageal adenocarcinoma are gastroesophageal reflux disease (GERD) and Barrett esophagus, a squamous-to-columnar cell metaplasia that predisposes to malignancy. Adenocarcinomas in Barrett esophagus are thought to arise through a sequence of growth-promoting, genetic alterations that accumulate until the cells have acquired the physiologic hallmarks of cancer proposed by Hanahan and Weinberg. Moreover, GERD and Barrett esophagus are associated with chronic esophagitis, and inflammation is a well known risk factor for cancer formation. The cell that gives rise to Barrett metaplasia is not known. It has been proposed that the metaplasia may arise from a change in the differentiation pattern of stem cells that either reside in the esophagus or are recruited to the esophagus from the bone marrow. Alternatively, it is possible that Barrett metaplasia develops through the conversion of one differentiated cell type into another. Regardless of the cell of origin, Barrett metaplasia ultimately must be sustained by stem cells, which might be identified by intestinal stem cell markers. An emerging concept in tumor biology is that cancer stem cells are responsible for sustaining tumor growth. If Barrett cancers develop from Barrett stem cells, then a therapy targeted at those stem cells might prevent esophageal adenocarcinoma. This report reviews the risk factors for Barrett esophagus and esophageal adenocarcinoma, the mechanisms by which genetic alterations might contribute to carcinogenesis in Barrett esophagus, and the role of stem cells in the development of Barrett metaplasia and adenocarcinoma.     

Molecular phenotype of spontaneously arising 4N (G2-tetraploid) intermediates of neoplastic progression in Barrett's esophagus

Elevated 4N (G(2)-tetraploid) cell populations are unstable intermediates in the development of many human cancers. However, 4N cell populations are intermixed with larger diploid fractions in vivo, limiting investigation of these key intermediates of neoplastic progression. Therefore, to study elevated 4N cell populations in human neoplasia, we used flow cytometry to purify populations of spontaneously arising TP53(wt) and TP53(mut) 4N cells from cell strains derived from premalignant Barrett's esophagus biopsies. Using oligonucleotide arrays, we identified 625 genes differentially expressed in at least one replicate 2N/4N comparison in each strain and in hTERT-immortalized cultures of the TP53(mut) strains. Strikingly, when hierarchically clustered, these data contained a large node of 124 genes that were up-regulated in 4N TP53(mut) cells in the absence of condensed chromosomes. Most of these genes function in G(2)-M to mediate processes such as chromosome condensation and segregation. These results describe the molecular phenotype of dysregulated G(2)-M functions and cell cycle checkpoints in a key intermediate of human neoplastic progression.     

Natural selection in neoplastic progression of Barrett's esophagus

Neoplasms progress to cancer through a process of natural selection. The rate of evolution, and thus progression is determined by three parameters: mutation rate, population size of the evolving neoplastic cells, and intensity of selection or rate of clonal expansion. All three parameters are reviewed in the context of Barrett's esophagus, a pre-malignant neoplasm. Although Barrett's esophagus is an ideal model for the study of neoplastic clonal evolution, similar studies may be carried out in a wide variety of human neoplasms. Evolutionary analyses provide insights for clinical management, including rates of progression to cancer and emergence of resistance to interventions.     

子宫内膜透明细胞癌69例预后因素分析

[目的]探讨子宫内膜透明细胞癌的预后因素。[方法]回顾性分析69例原发性子宫内膜透明细胞癌患者的临床资料。[结果]术前诊刮准确率为69.8%。临床分期、宫颈受累、累及附件、宫外转移、腹水细胞学、脉管间隙受侵、治疗方式及复发与患者预后相关（P〈0.05）。Cox回归分析显示腹水细胞学、脉管间隙受侵、治疗方式及复发情况是影响子宫内膜透明细胞癌患者预后的独立危险因素。[结论]子宫内膜透明细胞癌诊刮准确率低。腹水细胞学、脉管间隙受侵、治疗方式及复发与否是影响子宫内膜透明细胞癌患者生存率的独立危险因素。     

Histopathologic characteristics of early adenocarcinoma in Barrett's esophagus

To elucidate the early events of cancer development in the columnar cell-lined lower esophagus, 13 esophagectomy specimens with early adenocarcinoma (T1) were histopathologically studied and the morphometry of the lesion was performed on a histologic map. Eleven (84.6%) of the 13 early Barrett's carcinomas were contiguous to both the distinctive specialized-type Barrett's mucosa and squamous epithelium. Furthermore, ten (76.9%) of the 13 tumors had residual squamous islands on the surface. These data suggest that carcinomas in Barrett's esophagus mostly develop at a place very close to the squamocolumnar epithelial border. The distance from the tumor center to the nearest squamous epithelium, including squamous islands, was 2 cm or less in all cases but one. Therefore, the authors conclude that the primary site of cancer development in Barrett's esophagus is the metaplastic columnar-lined area, particularly of specialized type, within 2 cm from the squamocolumnar epithelial border.     

Barrett's esophagus in three children after antileukemia chemotherapy

Barrett's esophagus, a columnar metaplasia of the lower esophagus that is usually associated with gastroesophageal reflux (GER), was found in three children on long-term antileukemia chemotherapy. Two of the children had been on a standard acute lymphoblastic leukemia (ALL) maintenance protocol with 2 to 3 years of methotrexate and 6-mercaptopurine administration. The third child received daunorubicin, cytosine arabinoside, and 6-thioguanine for treatment of acute myelogenous leukemia (AML). None of the patients had clinical or pathologic evidence of GER disease. We propose that the Barrett's esophagus in these patients did not result from the usual peptic esophagitis, but rather from chemotherapy-induced esophageal mucosal injury.     

Genomic alterations in malignant transformation of Barrett's esophagus

The incidence of adenocarcinoma in Barrett's esophagus has been increasing rapidly over the past decades. Neoplastic progression is characterized by three well-defined premalignant stages: metaplasia, low-grade dysplasia, and high-grade dysplasia. A genome-wide overview, based on comparative genomic hybridization, was performed, evaluating 30 Barrett's adenocarcinomas and 25 adjacent precursors, i.e., 6 metaplasias, 9 low-grade dysplasias, and 10 high-grade dysplasias. The frequency of losses and gains significantly increased in the subsequent stages of malignant transformation. Losses of 5q21-q23, 9p21, 17p12-13.1, 18q21, and Y were revealed in low-grade dysplasias. This was followed by loss of 7q33-q35 and gains of 7p12-p15, 7q21-q22, and 17q21 in high-grade dysplasias along with high-level amplification (HLA) of 7q21 and 17q21. In the invasive cancers, additional losses of 3p14-p21, 4p, 4q, 8p21, 13q14-q31, 14q24.3-q31, 16q21-q22, and 22q as well as gains of 3q25-q27, 8q23-24.1, 12p11.2-12, 15q22-q24, and 20q11.2-q13.1 were distinguished along with HLAs of 8p12-p22 and 20q11.2-q13.1. Approximately one-third of the alterations in the dysplasias were also found in the adjacent adenocarcinomas, illustrating that multiple clonal lineages can be present in Barrett's esophagus. Novel findings include loss on 7q, gain on 12p, and the observation of several HLAs in high-grade dysplasias. Furthermore, loss of 7q33-q35 was found to represent a significant distinction between low-grade and high-grade dysplasia (P = 0.01), whereas loss of 16q21-q22 and gain of 20q11.2-q13.1 were disclosed to significantly discriminate between high-grade dysplasia and adenocarcinoma (P = 0.02 and P = 0.03, respectively). This inventory of genetic aberrations increases our understanding of malignant transformation in Barrett's esophagus and might provide useful biomarkers for disease progression.     

Double Adenocarcinoma in Barrett's Esophagus: A Case Report

At the National Cancer Center Hospital in Tokyo, a patient withBarrett's esophagus developed double adenocarcinoma of the esophagus.One carcinoma was located in the midesophagus and the otherjust above the anatomic cardia. Esophagoscopic examination withbiopsy revealed two carcinomas surrounded with columnar epitheliumand ectopic islets of gastric mucosa situated in the postcricoidregion. There was no ulcer or stricture in the esophagus. Thepatient received subtotal esophagectomy and survived the operation.Microscopically, depth of invasion of the proximal cancer wasto the proper muscle, and that of the distal one was to thesubmucosal layer. There was metastasis to two lymph nodes. Therewas no sign of inflammation or ulcer in the esophagus.