中医药结合放疗治疗食管癌及机制的研究进展

近年来,食管癌精确放疗技术能有效提高治疗增益比,最大限度减少肿瘤周围正常组织的受照量,放疗反应及并发症却不可避免,同时由于肿瘤生物学特性和患者个体差异,放射敏感度亟待提高。中医重视整体,调节机体平衡,在抗癌、减少放射性损伤和提高放疗疗效等方面具有优势。中医药结合放疗治疗食管癌是中国特色肿瘤诊治模式。本文就中医药结合放疗增敏减毒作用及机制研究做一综述。

食管罕见恶性肿瘤临床探讨

目的探讨食管罕见恶性肿瘤的临床病理特点及预后。方法对1992年3月—2008年3月共收治71例患者的临床病理资料进行回顾性分析。结果术后病理:癌肉瘤48例,恶纤组为恶性纤维组织细胞瘤8例,类癌5例(典型类癌1例、不典型类癌4例),淋巴瘤3例,恶性黑色素瘤3例,横纹肌肉瘤2例,平滑肌肉瘤2例。并发症发生率9.86%(7/71)。无手术死亡。术后1、3、5年生存率分别为:71.01%、54.00%、44.12%。结论食管癌肉瘤、恶性纤维组织细胞瘤、典型类癌、横纹肌肉瘤与平滑肌肉瘤预后较好,食管恶性黑色素瘤、恶性淋巴瘤、非典型类癌预后较差。手术切除是首选及主要治疗手段。

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.

Correlation between c-erbB-2 and P-glycoprotein Expression in Esophageal Carcinoma

Objective： To investigate the correlation between c-erbB-2 and multidrug resistance （MDR） and its clinical significance, Methods： Immunohistochemistry stain was used to examine the expression of c-erbB-2 and flow cytometry was used to detect the expression of P-glycoprotein （P-gp） in samples from 46 patients with esophageal carcinoma. Results： The positive expression rate of c-erbB-2 was 26.1% （12/46） in the 46 cases of esophageal carcinoma, of which 4 cases being low expression and 8 cases mediumhigh expression. The positive expression rate of P-gp was 60.9% （28/46） in the 46 cases of esophageal carcinoma, of which 6 cases being low expression, 13 cases medium expression and 9 cases high expression. Comparing c-erbB-2 with P-gp expression in different lymph node metastasis statuses showed that there was significant difference （P〈0.01） between P-gp expressions with lymph node metastasis （31.09%±5.33%） and without lymph node metastasis （8.04%±3.03%） when c-erbB-2 expression was positive. Comparing c-erbB-2 with P-gp expression in different TNM stages of esophageal carcinoma showed that there was significant difference （P〈0.01） between P-gp expressions in HI Ⅳ stage （33.68%±5.51%）and in Ⅱ stage patients （9.30%±2.78%） when c-erbB-2 expression was positive. The tumor＇s size and differentiation degree were not related to c-erbB-2 and P-gp expression. Conclusion： The high level of P-gp expression was related to the positive expression of c-erbB-2 with the lymph node metastasis in clinical Ⅲ-Ⅳ stage patients of esophageal carcinoma, suggesting that the double positive might lead to a poor prognosis. However, when the c-erbB-2 expression was negative, the lymph node metastasis and clinical staging were not related to the P-gp expression in esophageal carcinoma patients.

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

Selective cyclooxygenase （COX）-2 inhibitors （coxibs） were developed as one of the anti-inflammatory drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs （NSAIDs）. However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis （FAP）, which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration （FDA） immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors.

Bile salts inhibit growth and induce apoptosis of human esophageal cancer cell line

AIM： To explore the effect of six bile salts, including glycocholate （GC）, glycochenodeoxycholate （GCEX：）, glycodeoxycholate （GDC）, taurocholate （TC）, taurochenodeoxycholate （TCDC）, taurodeoxycholate （TDC）, and two bile acids including cholic acid （CA） and deoxycholic acid （DCA） on esophageal cancer Eca109 cell line. METHODS： Eca109 cells were exposed to six bile salts, two bile adds and the mixed bile salts at different concentrations for 24-72 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide （MTT） assay was used to detect the cell proliferation. Apoptotic morphology was observed by phase-contrast video microscopy and deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） assay. Sub-G1 DNA fragmentations and early apoptosis cells were assayed by flow cytometry （FCM） with propidium iodide （PI） staining and annexin V-FITC conjugated with PI staining. Apoptosis DNA ladders on agarose were observed. Activation of caspase-3 was assayed by FCM with FITC-conjugated monodonal rabbit anti-active caspase- 3 antibody and expressions of Bcl-2 and Bax proteins were examined immunocytochemically in 500μmol/L-TCinduced apoptosis cells. RESULTS： Five bile salts except for GC, and two bile acids and the mixed bile salts could initiate growth inhibition of Ecal09 cells in a dose- and time-dependent manner. TUNEL, FCM, and DNA ladder assays all demonstrated apoptosis induced by bile salts and bile acids at 500 μmol/L, except for GC. Early apoptosis cell percentages in Eca109 cells treated with GCDC, GDC, TC, TCDC, TDC, CA at 500 μmol/L for 12 h, DCA at 500 μmol/L for 6 h, and mixed bile salts at 1 000 μmol/L for 12 h were 7.5%, 8.7%, 14.8%, 8.9%, 7.8%, 9.3%, 22.6% and 12.5%, respectively, all were significantly higher than that in control （1.9%）. About 22% of the cell population treated with TC at 500 μmol/L for 24 h had detectable active caspase-3, and were higher than that in the control （1%）. Immunocytochemical assay suggested that TC down-regulated Bcl-2 protein level and up-regulated Bax protein level. CONCLUSION： GCDC, GDC, TC, TCDC, TDC, CA and DCA, except for GC, can inhibit growth and induce apoptosis of esophageal cancer Eca109 cells. Activation of caspase-3, decreased Bcl-2 protein and increased Bax protein are involved in TC-induced apoptosis of Eca109 cells.

Clinical application of metallic stents in treatment of esophageal carcinoma

AIM: To evaluate the effects of self-expanding metal stents (SEMS) in patients with malignant esophageal obstruction and to analyze their prognosis and complications. METHODS: Seventy-four metallic stents were placed under fluoroscopic guidance in 66 patients with esophageal obstruction secondary to carcinoma, of whom, 6 cases were complicated by fistula. RESULTS: After seventy-two stents were successfully used in 66 cases without any severe complications (technical successful rate was 97%), the dysphagia score improved from 3.3±0.6 to 0.8±0.5 (P<0.01), and life quality improved significantly in all these patients. All fistulae were sealed immediately after coated stents were inserted in the six patients. New stents were placed in two patients: the stent migrated more than 2 cm, in one patients and the stent slipped into stomach in the other. Minor bleeding was found only in 28 patients during the operation. Reobstruction was found in 12 patients, but was successfully cured under endoscopy. The survival rate was 78%, 57% and 11% for 6 mo, 1 year and 2 years respectively. CONCLUSION: Placement of SEMS is a simple, safe, quick and efficient surgical method for treating esophageal carcinoma obstruction. It may be used mainly as a palliative treatment of esophageal obstruction secondary to carcinoma.

Expression and significance of heat shock protein 70 and glucose-regulated protein 94 in human esophageal carcinoma

AIM: To investigate the expression and significance of heat shock protein 70 (HSP70) and glucose-regulated protein 94 (grp94) in human esophageai carcinoma and adjacent normal tissues. METHODS: The expression of HSP70 and grp94 in 78 human esophageai cancer and adjacent normal tissues was studied by immunohistochemistry and pathology photograph analysis. RESULTS: Both esophageai cancer and adjacent normal tissues could express HSP70 and grp94. Of the 78 cases of esophageai carcinoma, 95.0%(72/78) showed positive HSP70, mainly stained in nuclei, while grp94 was mainly stained in cell plasma, and the positive rate was 71.8% (56/78).There was a significant difference in the expression of HSP70 and grp94 between esophageai cancer and adjacent normal tissues (P<0.01). Compared with adjacent normal tissues, there was a significant difference between differential types and HSP70 expression (P<0.01). CONCLUSION: HSP70 and grp94 express differently in cell plasma and nuclei. The expression intensity of HSP70 is related to the differentiation of esophageai carcinoma.

Metastatic basaloid-squamous cell carcinoma of the esophagus treated by 5-fluorouracil and cisplatin

Basaloid squamous cell carcinoma （BSC） of the esophagus is a rare malignant disease. We report here a patient with recurrent esophageal BSC, who was successfully treated by systemic chemotherapy containing 5-fluorouracil （5-FU） and cisplatin （CDDP）. A 57-year-old woman was diagnosed as having SCluamous cell carcinoma of the esophagus upon endoscopic examination. Curative esophagectomy with lymph node dissection was performed under the thoracoscope. The pathological diagnosis of the surgical specimen was BSC. Five months after operation, the patient was diagnosed as having a recurrence of the BSC with metastases to the liver and spleen, and a right paraclavicular lymph node. She was given systemic chemotherapy consisting of continuous infusion of 800 mg/d of 5-FU and 3 h infusion of 20 mg/d of CDDP for 5 consecutive days every 4 wk. The metastatic lesions in the spleen and right paraclavicular lymph node disappeared, and the liver metastasis was apparently reduced in size after 2 courses of chemotherapy. The tumor regression was seen over 6 courses, with progression afterwards. Although subsequent treatment with CPT-11 and CDDP was not effective, docetaxel and vinorelbine temporarily controlled the tumor growth for 2 mo. 5-FU and CDDP combination may be useful for the patients with advanced BSC.

Esophagus and regenerative medicine

In addition to squamous cell carcinoma,the incidence of Barrett's esophagus with high-grade dysplasia and esophageal adenocarcinoma is rapidly increasing worldwide.Unfortunately,the current standard of care for esophageal pathology involves resection of the affected tissue,sometimes involving radical esophagectomy.Without exception,these procedures are associated with a high morbidity,compromised quality of life,and unacceptable mortality rates.Regenerative medicine approaches to functional tissue replacement include the use of biological and synthetic scaffolds to promote tissue remodeling and growth.In the case of esophageal repair,extracellular matrix(ECM) scaffolds have proven to be effective for the reconstruction of small patch defects,anastomosis reinforcement,and the prevention of stricture formation after endomucosal resection(EMR).More so,esophageal cancer patients treated with ECM scaffolds have shown complete restoration of a normal,functional,and disease-free epithelium after EMR.These studies provide evidence that a regenerative medicine approach may enable aggressive resection of neoplastic tissue without the need for radical esophagectomy and its associated complications.

Alterations of glutathione S-transferase and matrix metalloproteinase-9 expressions are early events in esophageal carcinogenesis

AIM: To investigate the role of glutathione S-transferase (GST) and matrix metalloproteinase-9 (MMP-9) expres-sions in the development and progression of reflux es-ophagitis-Barrett’s metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.METHODS: GST and MMP-9 expressions were analyzed in 51 paraffin-embedded tissue samples by immunohisto-chemistry including patients with reflux esophagitis (n = 7), Barrett’s metaplasia (n = 14), Barrett and esophagi-tis (n = 8), Barrett and dysplasia (n = 7), esophageal adenocarcinoma (n = 8) and a control group without any histological changes (n = 7). Immunostaining was determined semiquantitatively. Statistical analysis with one-way ANOVA, LSD test and correlation analysis were performed. P value of < 0.05 was considered significant.RESULTS: GST expression was significantly higher while MMP-9 expression was significantly lower in control group compared to Barrett’s metaplasia and the other groups. No major changes were observed between Bar-rett, esophagitis, and Barrett and concomitant esophagi-tis. Barrett and concomitant dysplasia, and adenocarci-noma revealed a significant lower expression of GST and higher levels of MMP-9 compared to all other groups. Adenocarcinoma showed almost no expression of GST and significantly higher levels of MMP-9 than Barrett and concomitant dysplasia. Alterations of GST and MMP-9 were inversely correlated (r = - 0.82).CONCLUSION: Decreased GST and increased ex-pression of MMP-9 in Barrett’s metaplasia-dysplasia-adenocarcinoma sequence as compared to normal tissue suggest their association with esophageal tumorigenesis. Loss of GST and gain of MMP-9 in Barrett with dyspla-sia compared to non-dysplastic metaplasia indicate that these alterations may be early events in carcinogenesis. Quantification of these parameters in Barrett’s esopha-gus might be useful to identify patients at higher risk for progression to cancer.

Endoscopic Mucosal Resection

Endoscopic mucosal resection is indicated in limited esophageal carcinomas with in?ltration of the mucosa. As submucosal cancer is combined with a rate of lymph node metastasis in up to 30% mucosectomy is not the procedure of choice. The main techniques of endoscopic mucosal resection are the “suck and cut” technique using a cap on the endoscope or a ligation device to create a pseudocroup of the carcinoma. Submucosal injection of saline or other solutions is recommended prior to diathermic mucosectomy in order to reduce the risk of perforation or haemorrhage. The long term results of endoscopic mucosal resection show tumor speci?c 5 year survival rates of about 97% especially if the indication is restricted to m1 and m2 mucosal carcinomas.

Angiopoietin-1 targeted RNA interference suppresses angiogenesis and tumor growth of esophageal cancer

AIM: To determine the inhibitory effect of the adenovirus- based angiopoietin-1 (Ang-1) targeted small interfering RNA expression system (Ad/Ang-1si) on the expression of the Ang-1 gene, cell growth and apoptosis in human esophageal cancer cell line Eca109. METHODS: siRNA-expressing adenovirus targeting Ang-1 gene was constructed using the Ad Easy System. Cultured Eca109 cells were transfected with Ad/Ang-1si (Eca109/Ang-1si), and Ad/si was used to infect Eca109 cells as control (Eca109/si). Ang-1 gene expression and concentration was determined with RT-PCR and ELISA, respectively. Human umbilical vein endothelial cell (HUVEC) migration and proliferation were analyzed. After s.c. injection into athymic nu/nu mice, the tumor growth, vessel density and apoptosis of each group was also determined. RESULTS: HUVEC migration induced by conditioned medium from Ang-1si-transfected Eca109 cells was significantly less than that induced by conditioned medium from Eca109 cells and control adenovirus- transfected Eca109 cells. Furthermore, after s.c. injection into athymic nu/nu mice, the tumor growth and cell apoptosis of Ad/Ang-1si -expressing Eca109 cells was significantly lower than that of parental or control adenovirus-transfected cells. Vessel density assessed by CD31 immunohistochemical analysis and Ang-1 expression by RT-PCR were also decreased. CONCLUSION: The targeting Ang-1 may provide a therapeutic option for esophageal cancer.

Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits apoptosis in esophageal squamous cell carcinoma cell line

Attrora-A kinase, a serine/threonine protein kinase, is a potential oncogene. Amplification and overexpression of Aurora-A have been found in several types of human tumors, including esophageal squamous cell carcinoma （ESCC）. It has been demonstrated that cells overexpressing Attrora-A are more resistant to cisplatin-induced apoptosis. However, the molecular mechanisms mediating these effects remain largely unknown. In this report, we showed that overexpression of Attrora-A through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells significantly promoted cell proliferation and inhibited cisplatin- or UV irradiation-induced apoptosis. Cleavages of caspase-3 and poly （ADPribose） polymerase （PARP） in Attrora-A overexpressing cells were substantially reduced after cisplatin or UV treatment. Furthermore, we found that silencing of endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells. In parallel, overexpression of Aurora-A potently upregulated the expression of Bcl-2. Moreover, the knockdown of Bcl-2 by siRNA abrogated the Aurora-A＇s effect on inhibiting apoptosis. Taken together, these data provide evidence that Aurora-A overexpression promoting cell proliferation and inhibiting apoptosis, suggesting a novel mechanism that is closely related to malignant phenotype and anti-cancer drugs resistance of ESCC cells.

Relationship between proliferative activity of cancer cells and clinicopathological factors in patients with esophageal squamous cell carcinoma

AIM: To assess whether the molecular markers of malignant tumors could improve the understanding of tumor characteristics, and to observe the characteristics of expression of cell cycle markers Ki-67 and cyclin A in esophageal carcinoma and to analyze the relationship between proliferative activity of cancer cells and clinicopathological factors. METHODS: Seventy of surgically resected esophageal squamous cell carcinoma (SCC) were examined by immun-ohistochemistry utilizing commercially available antibodies. Nuclear staining was regarded as a positive result. At least 50 fields in each tumor and non-tumor section were evaluated at a medium power (×200) to determine the proportion of tumor cells and the staining intensity of nuclei in the entire sections. RESULTS: Ki-67 and cyclin A were only expressed in base cells of normal esophageal mucosa. The positive immuno-staining of nuclei of SCC was significantly higher than that in normal esophageal mucosa (t = 13.32 and t = 7.52, respectively, P<0.01). The distribution of positively stained was more diffuse and stronger in poorly differentiated SCC. Both Ki-67 and cyclin A expressions were related to histological grades of tumors (t = 3.5675 and t = 3.916; t = 2.13, respectively, P<0.05) but not to the sex and age of the patients, tumor size, lymphatic invasion, location, or stage grouping. CONCLUSION: The proliferative activity of cancer cells may be understood by immunohistochemistry of Ki-67 and cyclin A in Chinese patients with esophageal SCC. These cell cycle markers may serve as an indicator of cancer cell proliferation rate. The overexpression of cell cycle markers Ki-67 and cyclin A suggests the poor SCC differentiation in patients with esophageal carcinoma.

Expression of the EphA2 Gene in Esophageal Carcinoma Tissues

OBJECTIVE To investigate the relationship of the EphA2 gene with the occurrence, invasion and metastasis of esophageal carcinoma. METHODS The expression of EphA2 mRNA was detected by RT-PCR and the EphA2 protein was estimated by immunohistochemistry (SP method) in both esophageal cancerous tissues and normal epithelial tissues. RESULTS The expression of EphA2 mRNA showed no difference between esophageal cancerous tissues and normal epithelium, and there appeared to be no correlation with differentiation of the cancerous tissues, the depth of infiltration or lymph node metastasis (P>0.05). However, the expression of the EphA2 protein was significantly higher in cancerous tissues compared to normal epithelial tissues (P<0.05). The expression of the EphA2 protein in a deeper invasive group and in a group with lymph node metastasis was significantly higher compared to a superficially invasive group and a group without lymph node metastasis (P<0.05). Its expression did not appear to be correlated with differentiation of cancerous tissues (P>0.05). CONCLUSION The occurrence of esophagus carcinoma and the formation of invasion and metastasis may be related to overexpression of the EphA2 protein but not to the level of mRNA, a finding which may due to up-regulation at the translation level or by increased protein stability.

A clinical study of thoracic esophageal carcinoma metastasis into abdominal lymph nodes

Objective The aim of this study was to analyze the potential of thoracic esophageal carcinoma to metas-tasize into abdominal lymph nodes. Methods The data on abdominal lymph node metastasis in 164 patients who had undergone resection of thoracic esophageal carcinoma were analyzed retrospectively and grouped according to tumor position in the upper, middle, or lower thoracic esophagus. The dif erence in tumor infiltration depth, dif erentiation degree, pathological type, pathological stage, and the metastasis rate in abdominal lymph nodes among the three groups was evaluated and the correlation of abdominal lymph node metastasis with tumor infiltra-tion depth, dif erentiation degree, and pathological type was analyzed. Results Clinical characteristics such as tumor infiltration depth, dif erentiation degree, pathological type, and pathological stage were not significantly dif erent between the patients with upper, middle, and lower thoracic esophageal carcinomas. Although there was a dif erence in the metastasis rate in abdominal lymph nodes between the three groups （6.9%, 27.4%, and 39.6% for the upper, middle, and lower thoracic esophageal carcinomas, respectively）, it was not statistical y significant. There was also no association between the rate of abdominal lymph node metastasis and tumor infiltration depth, dif erentiation degree, and pathological type. Conclusion Esophageal carcinoma specifical y metastasizes into lymph nodes. If the tumor infiltrates the upper thoracic submucosa, it could metastasize down to abdominal lymph nodes via the lymphatic cap-il ary net. The majority of esophageal carcinomas were of T1b or higher pathological stage at the diagnosis, indicating infiltration of the submucosa. Thus, tumors of the early stage, high degree of dif erentiation, or position in the upper thoracic esophagus were not less prone to metastasis into abdominal lymph nodes. Therefore, routine abdominal lymph node dissection during radical surgery for esophageal carcinoma is necessary.

Overexpression of TLR3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma

AIM: To investigate the expression of Toll-like receptor (TLR) 3, TLR4, TLR7 and TLR9 in esophageal squamous cell carcinoma (ESCC). METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry were used to analyze the expression of TLR3, TLR4, TLR7 and TLR9 mRNA and protein in samples from 87 esophageal cancer patients consisting of both tumor and normal tissue. RESULTS: A significant increase in TLR3, TLR4, TLR7 and TLR9 mRNA levels was detected in ESCC samples. Tumors exhibited high TLR protein expression, (70.1%, 72.4%, 66.7% and 78.2% for TLR3, TLR4, TLR7 and TLR9, respectively, P < 0.05). Nevertheless, a significant percentage of tumors also exhibited TLR4 expression in mononuclear inflammatory cells (48.3%) and TLR9 expression in fibroblast-like cells (60.9%). Tumors with high TLR3 expression in tumor cells or high TLR4 expression in mononuclear inflammatory cells were significantly associated with a higher probability of lymph node metastasis and increased depth of invasion. However, tumors with high TLR9 expression in fibroblast-like cells were associated with low probabilities of invasion and metastasis. There was no significant variation between the expression of TLR3, TLR4, TLR7 and TLR9 among different ethnic groups. CONCLUSION: TLR3, TLR4, TLR7 and TLR9 expression appears important to the biological pathogenesis of ESCC. TLRs may represent therapeutic targets for ESCC.

Multiple von Meyenburg complexes mimicking diffuse liver metastases from esophageal squamous cell carcinoma

Von Meyenburg complexes are benign liver lesions consisting of adenomatous bile duct proliferates. We present two patients suffering from esophageal cancer accompanied by the occurrence of yon Meyenburg complexes. Preoperative computerized tomography （CT） of the liver had not shown these lesions. In one of the patients, diffuse nodular manifestation was found in both liver lobes, mimicking diffuse hepatic metastases. Intraoperative frozen section revealed the benign nature of the lesions in both cases. The patients underwent esophageal resection without complications. To the best of our knowledge, the coincidence of von Meyenburg complexes and esophageal cancer has never been reported before. This uncommon entity should be taken into consideration as a differential diagnosis of liver lesions in malignancies. It underlines the importance of intraoperative frozen section for liver lesions of unknown origin.

Caspase-cleaved cytokeratin-18 and tumour regression in gastro-oesophageal adenocarcinomas treated with neoadjuvant chemotherapy

AIM:To examine cytokeratin-18(CK-18) and caspasecleaved CK-18 expression in tumours and correlate with clinicopathological outcomes including tumour regression grade(TRG) response.METHODS:Formalin-fixed human gastro-oesophageal cancers were constructed into tissue microarrays.The first set consisted of 122 gastric/gastro-oesophageal cancer cases not exposed to neoadjuvant chemotherapy and the second set consisted of 97 gastric/gastrooesophageal cancer cases exposed to pre-operative platinum-based chemotherapy.Expression of CK-18 and caspase-cleaved CK-18 was investigated using immunohistochemistry.RESULTS:CK18 was commonly expressed in gastrooesophageal tumours(92.6%).Fifty-six point seven percent of tumours previously exposed to neoadjuvant chemotherapy were positive for caspase-cleaved CK-18 expression compared to only 24.6% of tumours not previously exposed to neoadjuvant chemotherapy(P = 0.009).In patients who received neoadjuvant chemotherapy,caspase-cleaved cytokeratin-18 expression correlated with favourable TRG response(TRG 1,2 or 3,P = 0.043).CONCLUSION:This is the largest study to date of CK-18 and caspase-cleaved CK-18 expression in gastrooesophageal tumours.We provide the first evidence that caspase-cleaved CK-18 predicts tumour regression with neoadjuvant chemotherapy.