Complete eradication of squamous cell carcinoma of the esophagus with combined chemotherapy and radiotherapy

Chemotherapy (with 5-fluorouracil and either mitomycin-C or cis-platinum) combined with radiotherapy was used either for palliation or as preoperative therapy in 67 patients with squamous cell carcinoma of the esophagus. In 25 patients having chemotherapy and 5000-6000 rads, good local palliation was obtained in 11 (49%) without surgery. In the remaining 25 patients, swallowing was restored with a variety of procedures (primarily Celestine tube or gastric bypass). The average survival time was seven months and two patients are still alive at 9 and 12.5 months. Of 42 patients receiving preoperative chemotherapy and radiotherapy, 35 had surgery. Of these, 13 (37%) had complete eradication of their tumors with no histologic evidence of carcinoma in the resected esophagus or associated lymph nodes. In another six (17%), the only evidence of tumor was small microscopic foci of cancer cells in the wall of the esophagus. The 6-, 12-, and 24-month survival rates for patients having surgery after the combined preoperative chemotherapy and radiotherapy were 83 per cent, 52 per cent, and 30 per cent, respectively. These results are far superior to those previously obtained.     

Immunohistochemical expression of bcl-2 protein in squamous cell carcinoma and basaloid carcinoma of the esophagus

In the present study, the expression of bcl-2 protein in esophageal squamous cell carcinoma (SCC) and basaloid carcinoma (BC) was immunohistochemically examined, and its relation to tumor progression and postoperative survival was determined in SCC.A total of 42 SCC and 4 BC tumor samples were fixed with formalin, embedded in paraffin, and stained using monoclonal bcl-2 protein antibody, clone 124. Immunoreactivity was semiquantitatively scored, and the staining results were compared with the pathologic features and survival rates. The cytoplasm of basal cells from the normal esophageal epithelium was stained. In some well- and moderately differentiated SCCs, bcl-2 protein-positive reaction was observed in the peripheral part of the tumor cord, but in poorly differentiated SCC, the cells were weakly or hardly stained. However, in BC, the cells were strongly stained. The immunoreactivity was positive in 45.2% of the SCCs and all of the BCs. There were no significant differences in pathological features or patient survival between the bcl-2 protein-positive and protein-negative SCCs. In conclusion, the expression was not related to tumor progression and had no prognostic significance in SCC. Conversely, BC had strong immuno-histochemical expression, probably associated with the differentiation of carcinoma cells simulating the basal cells of the esophagus.     

MTA1表达与胸中段食管鳞癌预后的相关性

目的 探讨MTA1表达与胸中段食管鳞癌预后的相关性.方法 回顾2002年1月至2004年1月间,手术治疗165例胸中段食管癌病人临床资料.采用免疫组化进行肿瘤转移相关基因1(metastasis-associated gene 1,MTA1)检测,采用Kaplan-meier法进行生存分析、用Cox回归分析判定独立预后因素.结果 T2和T3病例MTA1表达率分别为13.3%和50%,两组差异有统计学意义(x2=13.2,P=0.00).有、无淋巴结转移者MTA1表达率分别为53.4%和31.2%,两组差异有统计学意义(x2=8.2,P=0.04).有、无MTA1蛋白表达者的5年生存率分别为18.3%和45.7%,两组差异有统计学意义(P=0.00).T2病例中,有、无MTA1蛋白表达者5年生存率分别为25.0%和50.0%,两组差异无统计学意义(P=0.20);T3病例中,有、无MTA1蛋白表达者的5年生存率分别为15.6%和40.6%(P=0.01),两组差异有统计学意义.pN0者中,有、无MTA1蛋白表达病例5年生存率分别为29.2%和54.7%(P=0.03),两组差异有统计学意义;pN1者中,有、无MTA1蛋白表达者5年生存率分别为12.8%和34.1%(P=0.04),两组差异有统计学意义.Cox回归分析结果显示,N分类和MTA1蛋白表达是独立的预后危险因素.结论 食管鳞癌不同的T、N分类中MTA1蛋白表达存在差别;MTA1蛋白过度表达者5年生存率降低;淋巴结转移和MTA1蛋白过度表达是独立的不利预后因素.     

Sarcomas and sarcomatoid tumor after radiotherapy of oral squamous cell carcinoma: analysis of 4 cases.

Radiation-induced sarcoma (RIS) or postirradiation sarcoma has been reported rarely as a long-term complication of radiation therapy (RT). We report 4 cases of oral sarcomas or sarcomatoid tumors with a rather short latency period after radiotherapy of the prior OSCC. Histopathological evaluation and immunohistochemical study were performed using a panel of markers including vimentin, cytokeratin, S-100, desmin, myoglobin, HHF-35, p53, and p16. All reported cases were positive for vimentin and negative for cytokeratin. Two cases were positive for myoglobin, desmin, or HHF-35, and were probably myogenic origin. One case was possibly a fibrosarcoma and the subclassification of the other one was not specified. Diverse expression of p53 and p16 was further observed in these 4 cases. Report of the complicated clinical processes and the analysis of genetic markers of these cases provide useful clinical and pathogenetic insights of mesenchymal malignancies associated with a status post OSCC radiation.     

Significance of immunohistochemical expression of cyclooxygenase-2 in squamous cell carcinoma of the esophagus

BACKGROUND: The focus of studies on cyclooxygenase-2 (COX-2) have been on its ability to mediate the biological behavior of human tumors including tumorigenesis, tumor progression, apoptosis, and differentiation. The aim of the current study was to elucidate a further finding on the clinicopathologic significance of immunohistochemical expression of COX-2 in esophageal squamous cell carcinoma (ESCC). METHODS: The immunohistochemical expression of COX-2 was examined for 76 specimens of ESCC and the correlation of COX-2 expression with clinicopathologic features was examined. RESULTS: Twenty-eight ESCCs (36.8%) had a strong expression of COX-2. The proportion of poorly differentiated SCCs among tumors with a strong expression of COX-2 (42.8%, 12 of 28) was significantly higher than that among tumors with a weak expression of COX-2 (16.7%, 8 of 48; P = .037). The depth of the tumors (P = .003) and the stage of the tumors (P = .015) were advanced significantly more progressively in ESCCs with a strong COX-2 expression. Univariate analysis showed that the prognosis of patients with ESCCs with a strong COX-2 expression was significantly poorer than that of patients with ESCCs with a weak COX-2 expression (P = .017). Multivariate analysis showed that only such tumor-related factors as lymphatic invasion (P = .004), venous invasion (P = .003), and stage of the tumors (P = .021) were found to be associated independently with worse prognosis of the patients with ESCC. CONCLUSIONS: Strong expression of COX-2 is correlated with tumor progression and poor differentiation in ESCC.     

Myocardial metastasis from squamous cell carcinoma of the esophagus

A 62-year-old woman was admitted to our hospital because of cancer of the middle thoracic esophagus. We performed a right transthoracic subtotal esophagectomy with systemic three-field lymphadenectomy. Histopathological findings resulted in a diagnosis of well-differentiated squamous cell carcinoma staged as pT3N0M0, pStage IIA, with clear surgical margins. Although she had no clinical symptoms, solitary cardiac metastasis located in the ventricular septum close to the apex was detected on the follow-up computed tomography scans during postoperative month 6. Regardless of chemotherapy followed by radiotherapy, she died of the cancer 17 months after the initial operation. An autopsy revealed metastatic lesions to the heart, lungs, kidneys, and liver. There were two metastatic masses in the heart without direct invasion from the outside of the heart. In cases of esophageal cancer, tumor spread to the heart is usually caused by direct invasion; thus, solitary hematopoietic cardiac metastasis is quite rare.     

Lymphatic spread in squamous cell carcinoma of the penis is independent of elevated lymph vessel density

OBJECTIVE

To examine the potential effect of tumour‐induced lymphangiogenesis in squamous cell carcinoma of the penis as a possible mechanism responsible for lymphatic spread.

PATIENTS AND METHODS

Specimens from 65 patients with invasive tumours (31 with and 34 without metastases) were evaluated for lymphatic vessel density (LVD) by the ‘hot‐spot’ method as the density of lymphatic endothelium hyaluronan receptor (LYVE‐1)‐positive lymphatic vessels per unit area of tissue. LVD was examined in peritumoral, intratumoral and normal tissue areas. The LVD of each tumour in these locations was calculated as the mean of the three highest lymph vessel counts in three to five hot‐spots. The nodal status was based on histopathological examination or an uneventful follow‐up of ≥2 years.

RESULTS

In all patients the mean (sd ) peritumoral LVD of 8.05 (3.14)/0.75 mm² was significantly higher than for intratumoral and normal tissue, of 4.67 (2.58) and 5.20 (1.87), respectively (P < 0.001). The slightly lower intratumoral LVD than in normal tissue was not significant. The peritumoral LVD was 8.07 (3.29) in metastatic and 8.03 (3.03) in non‐metastatic carcinomas. The intratumoral LVD was 5.13 (3.01) in node‐positive carcinomas and 4.28 (2.15) in tumours with no lymphatic node metastasis (LNM). Comparing tumours with and without LNM, there was no statistically significant difference between intra‐ and peritumoral LVD.

CONCLUSION

Increased LVD does not significantly affect the lymphatic spread in penile carcinomas, indicating that there must be alternative mechanisms that selectively enable tumour cells to invade lymph vessels and to metastasize into the lymph nodes.     

Distant metastases after definitive radiotherapy for squamous cell carcinoma of the head and neck

PURPOSE: To analyze parameters that influence the risk of distant metastases after definitive radiotherapy. METHODS: Between 1983 and 1997, 873 patients were treated with definitive radiotherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate risk factors that might influence the risk of distant metastases. RESULTS: The 5-year distant metastasis-free survival rate was 86%. Univariate analyses revealed that the risk of distant metastases was significantly influenced by gender (p =.0092), primary site (p =.0023), T stage (p <.0001), N stage (p <.0001), overall stage (p <.0001), level of nodal metastases in the neck (p <.0001), histologic differentiation (p =.0096), control above the clavicles (p <.0001), and time to locoregional recurrence (p <.0001). Multivariate analysis of freedom from distant metastases revealed that gender (p =.0390), T stage (p <.0001), N stage (p =.0060), nodal level (p <.0001), and locoregional control (p <.0001) significantly influenced this end point. Multivariate analysis revealed that gender (p =.0049), T stage (p <.0001), N stage (p <.0001), and locoregional control (p <.0001) significantly influenced cause-specific survival. CONCLUSIONS: The risk of distant metastases after definitive radiotherapy is 14% at 5 years and is significantly influenced by gender, T stage, N stage, nodal level, and locoregional control.     

Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma

BACKGROUND: Serine proteases have important roles in tumor invasion and metastasis, and their inhibitors, serine protease inhibitors (serpins), are attractive targets for therapeutic strategies. On chromosome 18q21, there is a cluster of serpins: maspin, headpin, and squamous cell carcinoma antigen 1 (SCCA1)/SCCA2. Others and we have reported that the expression of these serpins is down regulated in head and neck squamous cell carcinoma (HNSCC) cells compared with normal squamous epithelial cells. In this study, we hypothesized that expression of SCCA1 is biologically disadvantageous to HNSCC cells. METHODS: HNSCC cell lines were transfected with a mammalian expression vector with SCCA1 cDNA. In vitro proliferation, migration, or invasive potential (matrigel assay) of the transfectants were assayed. In addition, the in vivo growth and invasion was analyzed using the floor-of-mouth model of nude mice. RESULTS: SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 expression significantly inhibited the in vitro invasion in matrigel assays. Furthermore, the in vivo growth and invasion in nude mice was also inhibited by SCCA1 expression. CONCLUSIONS: Overexpression of SCCA1 in a HNSCC cell line inhibited its invasive potential. Loss of expression of the serpin SCCA1 may play a role in the malignant progression of HNSCC.     

p53 Overexpression in squamous cell carcinoma of the esophagus

Background: Coastal South Carolina has a high incidence of squamous cell carcinoma of the esophagus (SCCE) among black residents. Overexpression and mutations of thep53 tumor suppressor gene have been noted in SCCE from other high-incidence regions. The purpose of this study was to determine the frequency ofp53 overexpression in this region both in patients with SCCE and in normal subjects. Methods: Normal and malignant tissue obtained at esophagoscopy and normal esophageal mucosa (NEM) from random autopsies were studied with monoclonal antibodies to thep53 gene product. Total cellular RNA was extracted from SCCE, reverse transcribed to complementary DNA, and a portion of thep53 gene was amplified via polymerase chain reaction and sequenced. Results: Immunohistochemical studies on SCCE from nine patients showed that six (67%) were positive, two (22%) were negative, and one was indeterminate forp53 over-expression. The corresponding normal samples showed that three (33%) hadp53-positive cells in the basal epithelial layer, whereas six did not. NEM from 18 random forensic cases displayedp53 overexpression in seven (39%). Eight of the nine tumors hadp53 mutations. Conclusions: p53 overexpression and mutations are frequently found in SCCE from patients in coastal South Carolina. Overexpression in normal epithelium from random autopsy cases may indicate an inherited or acquired predisposition in this geographic region. Presented at the 47th Annual Cancer Symposium of the Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Resection margin for squamous cell carcinoma of the esophagus.

OBJECTIVE: The safe resection margin in esophagectomy for esophageal squamous cell carcinoma (SCC) was determined based on the extent of epithelial and subepithelial accessory lesions from the main lesions of esophageal SCC. BACKGROUND: There have been many reports on the high incidence of a positive resection margin for esophageal cancer. Although there were some studies on the relationships of the proximal clearance to postoperative local recurrence, no pathologic study on the resection margin has been reported. METHODS: Four hundred twenty specimens of a whole resected esophagus were examined histopathologically and the longitudinal length from the main lesion to the five types of accessory lesions was measured on microscopic slides. RESULTS: Contiguous intraepithelial carcinoma existed in 69 (46%) of 150 sites of main lesions restricted to the mucosa or submucosa and subepithelial lesions existed in 131 (54%) of 245 sites and 82 (55%) of 150 sites of main lesions invading an adventitia and into neighboring structures, respectively. The risk of a positive resection margin due to subepithelial lesions was below 5% at 10 mm in the main lesion, restricted to the submucosa or the muscularis propria, and at 30 mm in the main lesion, invading the adventitia in the potentially curative operation cases. CONCLUSION: These clearances of the resection margin, in which the risk of a positive resection margin is below 5%, are acceptable, although these clearances should only be accepted after the extent of epithelial accessory lesions is accurately determined by the Lugol's stain method.     

同时性重复癌(食管鳞癌、肺腺癌)1例

1.病例介绍 患者男,69岁,2004年12月因胃胀不适在外院行胃镜检查发现中段食管中分化鳞癌,确诊后行食管内放疗数次,未手术和化疗.2005年5月来我院复查胃镜见食管距门齿35 cm处见一0.3 cm×0.3 cm斑样隆起,病理活检示:可见异形细胞.     

Definitive radiotherapy for T1 and T2 squamous cell carcinoma of the tonsil

Background. To assess whether survival or local control of early squamous cell carcinoma of the tonsil has been compromised by a moderate-dose approach. Methods. Between 1970 and 1989, 185 patients with SCCa of the tonsil were seen at our institution. Fifty-three patients with T1 (30) and T2 (23) lesions treated with definitive radiotherapy were reviewed. Median follow-up was 60 months. The effects of total dose and site of the primary on survival and local regional control were analyzed. Results. Three-year determinate survival was 77%. Mean total dose was 63.1 Gy. Site of the primary significantly affected survival (86% for fossa, 54% for pillars, p < 0.025). Local control at 2 years was 81% and was independent of dose ≥ 63 Gy or site of the primary. Grade 4 complications defined by the RTOG/EORTC Acute Morbidity criteria occurred in three patients. Conclusions. Tumor doses on the order of 63 Gy or less result in excellent local control and survival rates for T1 and T2 carcinomas of the tonsil. Local control rates are better for fossa lesions than for pillar lesions. © 1995 Jons Wiley & Sons, Inc.     

食管鳞癌切除术后切缘癌残留的影响因素及预后

目的 探讨食管鳞癌切除术后切缘癌残留的影响因素和预后,评价术后补救性治疗的价值.方法 回顾性总结中山大学肿瘤防治中心1997年1月至2003年6月连续收治的1074例行食管鳞癌切除术患者的临床与病理资料,分析肿瘤分化程度、部位、病变长度、切口选择、吻合位置、T分期、N分期与切缘癌残留发生率的关系,并通过生存分析探讨补救性治疗的方式.结果 本组44例（4.3%）出现切缘癌残留.食管端切缘癌残留在病变位于胸上段时发生率为6.5%;胃端切缘癌残留在病变位于胸下段时发生率为0.8%.切缘癌残留发生率随T分期和N分期的增加而升高（均P＜0.05）.Logistic回归分析显示,T分期和N分期是术后切缘癌残留发生的危险因素.切缘癌残留患者3年生存率为22.7%.生存时间（25.2±3.3）个月.术后行补救性治疗者20例（45.5%,其中行放疗18例,行联合放化疗2例）：另24例（54.5%）未行补救性治疗.术后行补救性治疗与未行补救性治疗患者的3年生存率分别为53.2%与7.8%（P=0.027）.结论 肿瘤浸润程度和淋巴结转移是食管鳞癌切除术后切缘癌残留发生的危险因素;术后行补救性治疗可明显提高生存率.     

Planned neck dissection after definitive radiotherapy for squamous cell carcinoma of the head and neck

BACKGROUND: To define the role of planned neck dissection after definitive radiotherapy for patients with node-positive squamous cell carcinoma of the head and neck. METHODS: Review of the pertinent literature. RESULTS: Radiotherapy alone produces a relatively high likelihood of regional control for patients with early-stage neck disease. Patients with more advanced neck disease have a higher probability of regional control if a planned neck dissection follows radiotherapy. However, for patients who have a complete response to radiotherapy, the likelihood of an isolated recurrence in the neck is low. Radiographic evaluation of the response to radiotherapy may better define the subset of patients who are likely to benefit from a neck dissection. CONCLUSIONS: Neck dissection after definitive radiotherapy improves regional control for patients with advanced neck disease. Patients who have a complete clinical and radiographic regional response to radiotherapy have a low probability of an isolated recurrence in the neck. It is advisable to proceed with a neck dissection for patients who have an equivocal response to radiotherapy, because the likelihood of salvage of an isolated recurrence in the neck is remote.