Clinicopathologic analysis of esophageal and cardiac cancers and survey of molecular expression on tissue arrays in Chaoshan littoral of China

AIM: To investigate clinical and pathologic data of esophageal carcinoma (EC) and cardiac carcinoma (CC) among residents in Chaoshan region of China. METHODS: Clinical and pathologic data of 9 650 patients with EC and 4 173 patients with CC in the Chaoshan population were collected and analyzed. Moreover, Chaoshan esophageal carcinoma tissue arrays were made for high-throughput study. RESULTS: Male to female ratio was 3:1 in patients with EC and 4.75:1 in CC. The average age of the occurrence of EC was 54.6 years, and of CC was 58.1 years. For both EC and CC, age at diagnosis was a little younger in Chaoshan region than in most other areas. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%); the second was the lower third (15.3%). The main gross type of esophageal carcinoma was ulcerative type (41.50%); the medullary type was the second (39.6%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer (96.4%); adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma (94.5%). Chaoshan esophageal carcinoma tissue arrays were easily for high-throughput study, and tissue cores with a diameter of 1.5 mm could better keep more structure for molecular expression study. CONCLUSION: Both EC and CC are common in males. The average occurrence age of EC and CC is younger in Chaoshan than in most other regions of China. The most commonly affected site of esophageal carcinoma was the middle third of esophagus (72.0%). Squamous cell carcinoma accounted for the overwhelming majority of esophageal cancer; adenocarcinoma accounted for the overwhelming majority of cardiac carcinoma. Tissue arrays technology is applicable for rapid molecular profiling of large numbers of cancers in a single experiment.     

Detection of HSV and EBV in esophageal carcinomas from a high-incidence area in Shantou China

An association between viral infection, particularly the human papillomavirus, and the development of esophageal carcinoma (EC) has been reported. However, reports concerning the relationship between herpes simplex virus (HSV) and Epstein-Barr virus (EBV) with EC are few. There are geographic variations in infection rates. This study was aimed to determine the co-incidence of infection of the two viruses' with esophageal carcinoma and the differentiation of cancer tissues and lymphocytes infiltration in the tumor stroma of the high-incidence area of Shantou China. To determine the association between viral infection (HSV and EBV) and EC, we applied in situ hybridization (ISH) and immunohistochemistry (IHC) in 164 esophageal carcinoma surgical specimens from the high-incidence area of Shantou China. HSV DNA and HSVI, II protein expression were found in 52 (31.7%) of the 164 tumors; EBV EBER and LMP-1 proteins were identified in only 10 (6.1%) carcinoma specimens by in situ hybridization and immunohistochemistry. In histopathology analysis, the positive cases of HSV appeared to be more predominant in well and moderately differentiated squamous cell carcinomas, and the positive cases of EBV were found in poorly differentiated squamous cell carcinomas or undifferentiated carcinomas with intense lymphoid infiltration. Our results confirm the involvement of HSV and EBV in esophageal carcinomas and the relationship between HSV and EBV infection and esophageal carcinoma cell differentiation with lymphocyte infiltration in the tumor stroma. However, the two herpes viruses, HSV and EBV, particularly the human HSV may be one of the etiological factors in development of this malignancy among the high-incidence population of Shantou China.     

Correlation of ABO blood group with clinicopathologic characteristics of patients with esophageal squamous cell carcinoma

The aim of the current study was to determine the nvolvement of ABO blood group in clinicopathologic features in squamous cell carcinoma (SCC) of the esophagus, that has not previously been studied fully. Two hundred and eighty four consecutive patients with esophageal SCC were enrolled for the study. The relationship between patients' ABO blood group and the clinicopathologic features was analyzed. The proportion of poorly differentiated SCC among patients with blood group O was significantly lower than in those patients with other blood types (P = 0.001). The mean size of the tumors in patients with blood group AB was significantly larger than those in patients with other blood groups. The proportion of tumors associated with venous invasion was significantly higher in patients with blood type A than those of tumors in other blood types (P = 0.007). The TNM stages of tumors in blood group AB were found to be significantly more advanced (P = 0.036) than other groups. The functional significance of ABO blood group distribution might be associated with biological behavior of SCCs. However, it was found not to be a clinical predictor for the prognosis of the patients with esophageal SCC.     

Endoscopic Identification of Esophageal Involvement by Carcinoma of the Stomach

Correlation between esophagoscopic findings of the lower esophagus and cardia and the extent of esophageal involvement by carcinoma of the stomach was studied in 67 patients operated upon for adenocarcinoma involving the cardia.
Of 44 patients with such endoscopic signs as a mass, with or without ulceration, mucosal elevation or thickened folds in the lower esophagus, 43 had carcinomatous invasion over 1 cm. from the esophagogastric mucosal junction. On the other hand, only two of 23 patients without those endoscopic signs had esophageal involvement more than 1 cm. above the junction line.
When the cardial orifice was stenotic or asymmetrically open, minimal esophageal involvement was noted in 10 patients. No tumorous invasion to the esophagus was seen in 13 patients with symmetrically open cardia. It seems appropriate to state that when endoscopic examination reveals signs suggestive of esophageal involvement by carcinoma of the stomach, thoracotomy should be performed to attain radical operation. This is so except for those with minimal carcinomatous involvement of the lower esophagus.     

Factors Involved in the Return of Peristalsis in Patients with Achalasia of the Cardia after Heller's Myotomy

Objective : To assess the reappearance of peristalsis in a group of 45 patients with achalasia of the cardia undergoing surgery and to analyze the factors involved in this phenomenon. Methods : According to the postoperative manometric data, the 45 patients were divided into two groups, depending on whether or not they presented a return of peristalsis. A statistical comparison of age, sex, duration of the disease, pre- and postoperative radiological diameter of the esophagus, classic or vigorous nature of the achalasia, and manometric data of the lower esophageal sphincter and esophageal body was made. Results : In 46.6% of the patients, peristalsis returned to the upper esophagus, and 100% of the waves were progressive; in 24.4%, peristalsis returned to the middle third also, but only 50% of the waves were progressive; and in 8.8% (four patients), peristaltic activity returned to the whole esophagus, but only 40% of the waves were progressive. The group of patients with a return of peristalsis had a shorter duration of dys-phagia, less preoperative dilation of the esophagus, and a greater contractile activity of the esophageal body. Conclusions : Return of peristalsis is a frequent phenomenon after myotomy in patients with achalasia of the cardia, especially in cases of short clinical evolution, little esophageal dilation, and a conserved contractile capacity, although its accurate production mechanism is unknown.     

肺癌、贲门癌及食管癌外周血的免疫调节因子及相关抗原自身抗体表达研究

目的肺癌、贲门癌、食管癌是胸部主要肿瘤,具有高发病率和死亡率的特点,早期发现和治疗肺癌、贲门癌及食管癌意义重大,本研究旨在探讨免疫调节分子及肿瘤相关抗体在肿瘤发病中的作用及相互影响,为发现肿瘤早期诊断的标志物提供理论依据。方法本研究中,选择7个分子(含3个免疫调节因子)及4个肿瘤相关抗原。使用生物信息学数据库对蛋白质结构和性质进行综合分析,并通过生物信息学软件对7个分子的多肽抗原片段进行设计。采用ELISA法对食管癌患者检测外周血及非小细胞肺癌患者多肽抗原的抗体水平,选择健康体检者为对照组,采用对照组超过250例健康体检者的混合血作为质控样本。使用SPSS18.0数据处理软件对相关数据进行统计学分析,卡方检验,(P0.05)具有统计学意义。结果与健康体检者水平相比,肺腺癌及肺鳞癌外周血anti-CD25IgG水平存在统计学意义(P0.05),对照组男女健康体检者anti-CD25IgG水平明显低于肺癌患者。anti-CD25IgG检测中,ESCC及NSCLC患者阳性率较对照组明显偏高。实验结果表明,诊断早期ESCC和NSCLC,anti-CD25IgG水平有助于提高其诊断性。抗体检测:肺癌、贲门癌及食管癌患者anti-P16Ig G在检测中,其水平是明显高于对照组的,但其临床诊断意义不明显。结论在肺癌、贲门癌及食管癌患者外周血中,anti-CD25IgG及anti-FOXP3IgG能为临床诊断提供依据;肺癌、贲门癌及食管癌与anti-P16IgG水平的改变具有相关性,但其阳性率不明显,其临床诊断价值有待深入研究。     

Alterations of p53 and PCNA in cancer and adjacent tissues from concurrent carcinomas of the esophagus and gastric cardia in the same patient in Linzhou,a high incidence area for esophageal cancer in northern China

AIM:To characterize the alteration and significance of p53 and PCNA in cancer and adjacent tissues of concurrent cancers from the esophagus and gastric cardia in the same patient.METHODS: P53 and PCNA protein accumulation in 25 patients with concurrent cancers from the esophagus and gastric cardia (CC, concurrent carcinomas of esophagealsquamous cell carcinoma and gastric cardia adenocarcinoma)were detected by immunohistochemical method (ABC).RESULTS: In CC patients, both esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA)tissues showed different positive immunostaining extent ofp53 and PCNA protein (P>0.05). The positive immunostainingrates for p53 and PCNA were 60 % (15/25) and 92 % (23/25), respectively in SCC; and 40 % (10/25) and 88 % (22/25), respectively in GCA. “Diffuse“ immunostaining patternwas frequently observed in both p53 and PCNA. High coincidence rates for p53 and PCNA positive staining were observed in SCC and GCA from the same patients, andaccounted for 56 % and 96 %. In SCC patients, with thelesions progressed from normal esophageal epithelium (NOR)to basal cell hyperplasia (BCH) to dysplasia (DYS) tocarcinoma in situ (CIS) to SCC. the oositive rates for p53were 27 %, 50 %, 50 %, 29 % and 72 %, and 55 %, 70 %,75 %, 71% and 93 % for PCNA, respectively. In GCA, with the lesions progressed from normal gastric cardia epithelium to DYS to CIS to GCA, the positive rates of p53 expression were 44 %, 27 %, 22 % and 36 % respectively, the difference was not significant; the positive rates of PCNA protein expression were 67 %, 64 %, 67 % and 86 %, respectively.The χ^2 test, Fisher‘s Exact Test, Mantel-Haenszel χ^2 Test and Kappa Test were used for the statistics.CONCLUSION: The high coincident alterations for P53 and PCNA in SCC and GCA from the same patient indicate the possibility of similar molecular basis, which provides important molecular basis and etiological clue for similar geographic distribution and risk factors in SCC and GCA.Chen H, Wang LD, Guo M, Gao Alterations of p53 and PCNA inSG, Guo HQ, Fan ZM, Li JL.cancer and adjacent tissuesfrom concurrent carcinomas of the esophagus and gastric cardiain the same patient in Linzhou, a high incidence area foresophaqeal cancer in northern China. World J Gastroenterol     

70岁以上食管癌和贲门癌患者的开胸手术分析

目的 探讨高龄食管癌和贲门癌患者的外科手术选择及围手术期处理方法 . 方法 回顾性分析1088例食管癌和贲门癌患者的临床资料,分为70岁以下(41～69岁)、70～74岁、75～79岁、80岁以上(80～90岁)4组.统计4组患者术后并发症、住院时间及预后,并对手术选择和围手术期治疗措施进行分析. 结果 70岁以上食管癌和贲门癌患者术后肺部感染、心律失常、精神症状和切口不愈的发生率明显上升,术后住院时间明显延长;80岁以上的高龄患者术后肺部感染发生率和术后住院时间较其他年龄段明显上升.全组痊愈1084例,死亡4例. 结论 在高龄食管癌和贲门癌患者中,了解开胸术后并发症发生状况,加强对肺部感染的预防和治疗是决定手术成败的关键.     

Radiotherapy of 180 cases of operable esophageal carcinoma

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Just a little heartburn?

Lagergren et al. performed a population-based, case-control study to investigate the possible association between gastroesophageal reflux (GER) and adenocarcinoma of the esophagus and gastric cardia. They demonstrated an odds ratio of 7.7 for esophageal adenocarcinoma in patients with GER symptoms. The frequency, severity, and duration of symptoms correlated with an increased risk of esophageal adenocarcinoma. A weaker association was noted for GER and adenocarcinoma of the gastric cardia. No association surfaced between GER and squamous cell carcinoma of the esophagus.     

The European experience with esophageal cancer limited to the mucosa and submucosa

In a survey concerning the diagnosis of esophageal cancer and especially early esophageal cancer (EEC) made during the years 1976 to 1980 we collected from all over Europe the results of 902,207 upper gastrointestinal endoscopies. There were 6,719 (0.7%) reports of esophageal carcinoma of which 51 (0.75%) were EEC. Only 8 patients with EEC were asymptomatic. The tumor was localized to the middle third of the esophagus in 24 cases, to the lower third in another 24 cases, and to the upper third in 3 cases. All patients had resection of the esophageal cancer. Thirty-one (60.7%) patients are still alive, but 6 show evidence of recurrence.     

Human papillomavirus DNA and P16(INK4A) expression in concurrent esophageal and gastric cardia cancers

AIM:To investigate the relationship between human papillomavirus (HPV) infection and concurrent esophagus and gastric cardia cancer from the same patient (CC) and examine the significance of P16 INK4A protein expression.METHODS:Polymerase chain reaction was used to detect the presence of HPV type16 (HPV16).The expression of P16 INK4A protein was detected using immunohistochemistry.RESULTS:Among the CC specimens,HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA),respectively (47% vs 29%),and two of both ESCC and GCA.P16 INK4A was highly expressed in both ESCC and GCA.In the HPV-associated positive CC,higher P16 INK4A expression was observed in the GCA than in the ESCC (75% vs 25%,P < 0.05).CONCLUSION:HPV16 as a correlated risk factor may play an important role in the development of ESCC and GCA.P16 INK4A may be a screening index in the HPVassociated carcinoma of gastric cardia.     

Polymorphisms of HLA-A and HLA-B genes in genetic susceptibility to esophageal carcinoma in Chaoshan Han Chinese

Esophageal carcinoma (EC) occurs at high rate in Chaoshan region of southern China. Human leukocyte antigen (HLA) polymorphism has been implicated in risk for various cancers. To investigate the impact of HLA-A and HLA-B polymorphisms on susceptibility to EC, a case–control study was conducted among 206 patients with esophageal squamous cell carcinoma and 524 controls from Chaoshan Han population. HLA-A and HLA-B polymorphisms were genotyped by polymerase chain reaction-sequence-specific primers. Genotypic association tests for dominant, recessive, and additive models, and haplotypic association were calculated using unconditional logistic regression. A*11 was identified in a recessive model as an only allele strongly associated with EC risk (odds ratios [OR]= 2.10, 95% confidence interval [CI]= 1.33–3.31) even after correction for multiple test. The haplotypes A*02-B*46 (OR = 1.53, 95% CI = 1.04–2.24) and A*11-B*51 (OR = 2.29, 95% CI = 1.20–4.40) showed association with increased risk for EC, whereas A*11-B*58 (OR = 0.00, 95% CI = 0.00–0.82) was associated with decreased risk, though the significance of these haplotypes was lost after correction. This is a first association study at genetic level identifying HLA-A and HLA-B-related variations in genetic susceptibility to EC among Chaoshan population. The variation pattern is likely to be EC-specific because it is different from that observed for nasopharyngeal carcinoma in the same study population and might, at least in part, explain the high rate of EC in this ethnic group.     

Fibrovascular esophageal polyp as a diagnostic challenge

Fibrovascular polyps are rare benign esophageal tumors that usually arise from the proximal third of the esophagus. We present the case of a 48-year-old man with a history of dysphagia and 7-kg weight loss over a period of 2 months. A barium swallow showed a distended esophagus with a tumor extending from the upper esophageal sphincter to the cardia. On a thoracic computed tomographic scan, a homogeneous intramural mass with a density of 22 Hounsfield units was seen, which extended throughout the entire esophagus. Fiberoptic endoscopy confirmed the presence an intramural tumor beginning at the upper esophageal sphincter and reaching to the cardia. The tumor was completely covered with mucosa, except for an ulcerated area at its distal end, which herniated into the stomach. On endoscopic ultrasound, the tumor appeared to grow submucosally and to respect the muscularis propria. Endoscopic biopsies from the ulcerated distal aspect of the tumor suggested a leiomyoma. None of the imaging modalities used revealed evidence of a polyp or intraluminal esophageal tumor. Rather, a potentially malignant extensive intramural tumor was suspected, and an esophagectomy was performed. Only at the time of removal of the specimen did it become evident that the tumor mass was located intraluminally with a pedicle in the region of the upper esophageal sphincter. The final pathological diagnosis was a giant fibrovascular polyp of the esophagus.     

幽门螺杆菌L型感染与食管癌及癌前病变中bcl-2表达关系的研究

目的研究幽门螺杆菌L型(HpL)感染对食管癌及癌前病变凋亡调节基因bcl2蛋白表达的影响,探讨Hp-L在食管癌发生发展过程中可能的致癌机制。方法应用免疫组化和革兰染色技术检测51例食管鳞状细胞癌(原位癌16例,浸润癌35例)及69例鳞状上皮增生性病变(单纯增生15例,轻、中、重度不典型增生分别为21例、18例、15例)和20例正常食管粘膜鳞状上皮组织中HpL型和bcl2蛋白的表达情况,对HpL型阳性和阴性组织的bcl2蛋白表达进行比较分析。结果不同组织类型HpL型检出率在中、重度不典型增生、原位癌、浸润癌均比较高(55.6%～62.9%),与正常组相比均有显著性差异(P<0.005)。在120例食管病变组织中,61例HpL型阳性者的bcl2蛋白表达阳性有48例,占78.7%;79例HpL型阴性者的bcl2蛋白表达阳性24例,占40.7%,两者比较有显著性差异(P<0.005)。各病变组中HpL型感染阳性组的bcl2蛋白表达阳性率高于HpL型阴性组的bcl2蛋白表达阳性率,其差异均有显著性(P<0.005～P<0.025)。表明HpL型感染与bcl2蛋白表达存在着相关性。结论HpL型可能通过影响bcl2蛋白表达,使食管粘膜上皮细胞凋亡调控异常而涉及食管癌的发生发展过程。     

Reconstruction techniques for hypopharyngeal and cervical esophageal carcinoma

Objective

To investigate the incidence of perioperative complications in patients with hypopharyngeal and cervical esophageal carcinoma who underwent three types of esophageal defect reconstruction procedures.

Methods

Clinical data from 105 patients with hypopharyngeal and cervical esophageal carcinoma who were treated at SUN YAT-SEN Memorial Hospital from January 2003 to February 2013 were retrospectively analyzed. Among these patients, 45 underwent a pectoral major muscle skin flap reconstruction following carcinoma resection (group A); 32 patients were treated with stomach replacement of the esophagus (group B), and 28 patients were treated with tube stomach replacement of the esophagus (group C). The incidences of perioperative complications were compared among these three groups.

Results

The incidences of anastomotic leakage, neck swelling, and incision infection were significantly lower in group C than in group A (P<0.05). The incidences of anastomotic leakage, reflux esophagitis, and thoracic stomach syndrome were significantly lower in group C than in group B (P<0.05).

Conclusions

Tube stomach replacement of the esophagus in the setting of hypopharyngeal and cervical esophageal carcinoma reduced the incidence of complications; therefore, it is a reasonable procedure for the management of esophageal defects.     

Circumscribed venous ectasia of the upper esophagus and "downhill" varices in primary disorders of esophageal motility

Felson and Lessure 1964 (1) described varicosities involving the upper third of the esophagus in patients without portal hypertension. Several etiological factors causing these "downhill" varices, e.g. bronchogenic carcinoma, retrosternal thyroid adenoma or mediastinal fibrosis, have been described. Since September 1989 ectatic esophageal veins or "downhill" varices were diagnosed in nine patients with dysphagia and/or non cardiac chest pain. Intrathoracic masses as a possible cause of "downhill" varices could not be diagnosed in any of these patients. Endoscopy of the upper gastro-intestinal tract revealed spiral esophageal contractions as a potential sign of a esophageal motor disorder in seven patients. By means of esophageal manometry "nutcracker"-esophagus was seen in two patients and diffuse esophageal spasm in three patients. On the basis of these findings primary esophageal motor disorders should be considered as a possible cause of ectatic veins in the proximal esophagus and "downhill" varices.     

Submucosal tumor (SMT)-like esophageal squamous cell carcinoma with gastric metastasis

We present here a case of submucosal tumor-like esophageal cancer with metastasis to the stomach. A 60-year-old man, whose ability to swallow was impaired, was admitted to Kyorin University School of Medicine Hospital. Gastrointestinal endoscopy demonstrated a small bulging mass in the lower esophagus and a large submucosal mass in the gastric cardia. The gastric lesion was growing rapidly and becoming easily hemorrhagic. It appeared rich in blood flow by angiography. Surgical treatment was adopted after a diagnosis of esophageal cancer and a gastric submucosal tumor was made. However, in the end, the gastric mass was identified as a metastasis from the esophageal squamous cell carcinoma. Moreover, the primary esophageal lesion displayed quite a special type of histology, a so-called submucosal tumor-like pattern, which was covered by normal epithelium and grew mainly in the submucosal layer of the esophagus. Gastric metastasis from esophageal cancer is relatively rare, and it is quite rare that an esophageal squamous cell carcinoma grows as a submucosal tumor. Finally, the patient died of pneumonia and metastasis to the liver on the 110th day of hospitalization. Intramural metastasis to the stomach from esophageal cancer should be treated in its advanced stage, and poor prognosis can be expected from aggressive treatment. It is necessary to recognize this complication so that appropriate therapy can be carried out on patients with esophageal cancer, and the situation needs to be carefully evaluated, including the stomach, both before and after treatment.     

A case of synchronous squamous cell carcinoma in the esophagus and stomach

Synchronous esophageal and gastric cancers with the pathologic features of a squamous cell carcinoma are extremely rare. A 57-year-old male visited our hospital with a history of hematemesis and was diagnosed with a synchronous cancer. He underwent a staging work-up, and the resectable lesion in the stomach was operated on following radiologic and endoscopic evaluations. The pathologic examination revealed a synchronous cancer consisting of squamous cell carcinoma in the distal esophagus and the cardia of the stomach. We report a case of a synchronous cancer that was successfully treated by surgical resection followed by concurrent chemoradiotherapy. We also discuss the hypothesis regarding the origin and presentation of the synchronous cancer and highlight the importance of careful surveillance by physicians at the time of diagnosis.