Histopathological evaluation of hyperthermo-chemo-radiotherapy for carcinoma of the esophagus

The effectiveness of preoperative hyperthermo-chemo-radiotherapy for 25 patients with carcinoma of the esophagus was histopathologically compared with findings in 104 patients treated preoperatively with irradiation only. The preoperative hyperthermo-chemo-radiotherapy increased the rate of "markedly effective" in the resected tissue, when compared with findings in cases of irradiation only. With regard to long survival rates, the 5-year survival rates of patients classed as "markedly effective" with preoperative combined therapy exceeded events in patients classed as "moderately effective," and "ineffective," with statistical significance. Preoperative hyperthermo-chemo-radiotherapy is the recommended treatment for patients with carcinoma of the esophagus.     

Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma.

Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery.     

Prospective randomized study of hyperthermia combined with chemoradiotherapy for esophageal carcinoma

From January 1988 to June 1992, 66 patients with resectable squamous cell carcinoma of the thoracic esophagus underwent preoperative adjuvant therapy. These patients were prospectively divided into two treatment groups; 32 were treated with radiofrequency wave local hyperthermia combined with chemoradiotherapy (hyperthermochemoradiotherapy; HCR), while the remaining 34 patients were treated with chemoradiotherapy alone (CR). There were no procedural complications in either group and the postoperative mortality was zero. In the HCR group, no viable cancer cells were found within the entire 5 mm-width slices of the resected specimen in eight patients (25%), while only two (5.9%) in the CR group (P < 0.05) demonstrated no viable cancer cells. The cumulative 3-year survival rate was 50.4% in the HCR group and 24.2% in the CR group. The present prospective trial demonstrated that the addition of hyperthermia to chemoradiotherapy resulted in a better local control and an improved long-term survival when treating patients with advanced esophageal carcinoma. © 1995 Wiley-Liss, Inc.     

DNA ploidy is closely linked to tumor invasion, lymph node metastasis, and prognosis in clinical gastric cancer

DNA ploidy microspectrophotometrically determined in 254 patients with gastric carcinoma was investigated from the standpoint of tumor invasion, lymph node metastasis, and prognosis. DNA distribution patterns were grouped into low and high ploidies. The 24.0% frequency in the high ploidy group, at the mucosal stage, increased in proportion to invasion into the deeper layers. There was a high incidence of lymph node metastasis in the high ploidy group, compared with the low ploidy group, in case of invasion beyond the mucosa. Widespread nodal involvement was frequent in the high ploidy group. The 5-year survival rate was 73.7% in patients of high ploidy, with a statistical difference compared to the 90.6% in those of low ploidy (P less than 0.01). In the multivariate analysis of 226 patients undergoing curative surgery, the DNA ploidy proved to be a major independent prognostic factor. These findings indicate a close correlation among DNA ploidy, tumor invasion and nodal involvement, and the significant clinical value of DNA analysis for predicting the prognosis in patients with gastric carcinoma.     

Prognosis of patients with advanced carcinoma of the esophagus with complete response to chemotherapy and/or radiation therapy: a questionnaire survey in Japan

BACKGROUND: We estimated the survival of patients with advanced carcinoma of the esophagus in Japan who achieved complete response (CR) with chemotherapy and/or radiation therapy. METHODS: A questionnaire was designed for patients with cancer of the esophagus with pretreatment stage II-IV (excluding organ metastasis [M1]), who were treated with chemotherapy and/or radiation therapy and achieved either a clinical CR continuing for more than 1 year, or a pathological CR in surgical specimens. All patients were treated between January 1, 1990, and December 31, 1997, in Japan. RESULTS: Of the 169 eligible patients for whom adequate data were available, 106 patients with continuing clinical CR were defined as group A and 63 with pathological CR as group B. The overall survival rates at 5 years were 62.4% in group A and 64.8% in group B. In each of groups A and B, there was no significant difference in overall survival among subgroups of patients classified by initial pretreatment clinical stage. In group A, the survival rate of patients with concurrent chemotherapy and radiation therapy was significantly better than the rates for patients with chemotherapy alone or radiotherapy alone. In group A, the frequency of first failure at the local site of esophageal carcinoma was 7.7%. Of the 12 patients in group B (19%) who died less than 1 year postoperatively, 6 died of postoperative complications. CONCLUSION: The effect of CR to chemotherapy and/or radiation therapy for carcinoma of the esophagus on survival was marked. In patients with esophageal carcinoma who achieve CR, the prognosis may be independent of the initial pretreatment stage. Local failure in group A patients remains a problem, however.     

Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus--a prospective randomized trial.

From 1988 to 1990, 53 patients with squamous cell carcinoma of the thoracic oesophagus underwent subtotal oesophagectomy after either preoperative hyperthermo-chemoradiotherapy (HCR therapy) or chemoradiotherapy without hyperthermia (CR therapy), in a prospective randomized trial carried out to examine the effects of hyperthermia given preoperatively. The two groups (27 patients given HCR therapy and 26 given CR therapy) were found to be comparable with regard to prognostic factors of age, site of carcinoma, TNM stage, etc. Following preoperative evaluation by an upper GI series and endoscopy, a subtotal oesophagectomy was done for all 53 patients. All the resected specimens, including the lymph nodes, were histopathologically examined, and the effects of preoperative treatment were evaluated by findings in the upper GI series and endoscopy, as well as based on the histopathology of the excised tissues. There were no viable cancer cells in the resected specimens of seven patients in the HCR therapy group (26.9%) and of two patients in the CR therapy group (7.7%). In addition, no hyperthermia complications were observed. The study suggests that preoperative HCR therapy may be a more beneficial therapy than preoperative CR therapy in patients with squamous cell carcinoma of the oesophagus who undergo a subtotal oesophagectomy.     

Reply to the Letter to the Editor

From 1988 to 1990, 53 patients with squamous cell carcinoma of the thoracic oesophagus underwent subtotal oesophagectomy after either preoperative hyperthermo-chemoradio-therapy (HCR therapy) or chemoradiotherapy without hyperthermia (CR therapy), in a prospective randomized trial carried out to examine the effects of hyperthermia given preoperatively. The two groups (27 paitents given HCR therapy and 26 given CR therapy) were found to be comparable with regard to prognostic factors of age, site of carcinoma, TNM stage, etc. Following preoperative evaluation by an upper GI series and endoscopy, a subtotal oesophagectomy was done for all S3 patients. All the resected specimens, including the lymph nodes, were histopathologically examined, and the effects of preoperative treatment were evaluated by findings in the upper GI series and endoscopy, as well as based on the histopathology of the excised tissues. There were no viable cancer cells in the resected specimens of seven patients in the HCR therapy group (26·9%) and of two patients in the CR therapy group (7·7%). In addition, no hyperthermia complications were observed. The study suggests that preoperative HCR therapy may be a more beneficial therapy than preoperative CR therapy in patients with squamous cell carcinoma of the oesophagus who undergo a subtotal oesophagectomy.     

Prognostic significance of tumor-host interaction in clinical gastric cancer: Relationship between dna ploidy and dendritic cell infiltration

DNA ploidy of tumor cells and the degree of infiltration of dendritic cells were determined in 93 gastric cancer tissue specimens, and the mechanisms of tumor-host interaction on the prognosis were investigated. DNA ploidy patterns were grouped into low and high ploidy, and the degree of infiltration of dendritic cells (DC) was graded into marked and slight infiltration. In the low ploidy group, the 5-year survival rates in patients with marked and slight DC infiltration were 80.7% and 61.5%, respectively (P < 0.05). In the high ploidy group, however, there were no significant differences. In cases of low ploidy, the incidence of lymph node metastasis was significantly lower in the marked DC infiltration group compared with findings in the slight DC group. Thus, markedly infiltrating dendritic cells in gastric cancer tissue may lead to prolongation of survival time for patients with a carcinoma of the low ploidy profile, by preventing widespread nodal involvement. © 1993 Wiley-Liss, Inc.     

Prognostic significance of DNA content with special reference to age in gastric cancer

The authors studied 93 patients who had undergone curative resection for advanced gastric cancer to assess the prognostic significance of DNA ploidy in relation to patient age. The cancers were classified as low and high-ploidy carcinomas and the patients were grouped by age (22-44 years, 45-64 years, 65-79 years). The incidence of high ploidy cancers increased with age. The 5-year survival rate increased with patient age in the low ploidy group whereas it decreased with patient age in the high ploidy group. There was a statistically significant difference (P less than 0.05) in the 5-year survival between our oldest patients with low (100%) and high ploidy (25.7%) gastric cancer. High ploidy cancers manifested a higher incidence of vessel invasion and lymph node metastasis. Our findings indicate that analysis of the DNA distribution pattern in gastric carcinoma is of prognostic value especially in older patients.     

Low proliferative activity is associated with a favorable prognosis in peripheral T-cell lymphoma

Peripheral T-cell lymphoma (PTCL) consists of a diverse group of post-thymic tumors bearing a mature T-cell phenotype and, excluding mycosis fungoides, comprises approximately 10-20% of the non-Hodgkin's lymphomas in the United States. This category of non-Hodgkin's lymphomas exhibits considerable morphological, immunological, and clinical diversity and is generally considered to be a high-grade malignancy. In the present study, paraffin-embedded biopsy specimens of lymph nodes from 31 patients with PTCL who were treated with curative intent were evaluated by flow cytometry for DNA ploidy and proliferative activity (PA). DNA ploidy was not predictive of the clinical outcome. However, low PA, defined by less than or equal to 10% of cells in S + G2M phase of cell cycle, was associated with a favorable prognosis. Patients with tumors having low PA had a significantly higher complete remission rate (100%) as compared to those with high PA (55%; P less than 0.02), and the predicted actuarial 4-year survival of those with low PA was 85% versus only 50% for those with high PA (P less than 0.04). This is the first report of the effects of PA and DNA ploidy in patients with PTCL who were treated with curative intent. Additional studies of similar patients are needed to confirm these findings.     

Flow cytometric DNA analysis is useful in detecting multiple genetic alterations in squamous cell carcinoma of the esophagus.

BACKGROUND: Although flow cytometric DNA analysis has been recognized to be a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus, the biologic significance of DNA aneuploidy remains to be elucidated. METHODS: Twenty-five patients with squamous cell carcinoma of the esophagus who underwent a curative subtotal esophagectomy were divided into 2 groups according to the DNA ploidy pattern. Multiple genetic changes, including the gene amplification of bcl-1, epidermal growth factor receptor, and c-myc, and the loss of heterozygosity of multiple tumor suppressor genes, including retinoblastoma, mutated in colorectal carcinoma, adenomatous polyposis coli, and deleted in colorectal carcinoma, in each case were investigated and the frequency of genetic alterations compared between both groups. In addition, the clinical outcome of these patients was also investigated. RESULTS: Eleven of 15 cases in the aneuploid group demonstrated at least 1 genetic change (73.3%) whereas only 2 of 10 cases in the diploid group did so (20.0%) (P<0.05). Both cases in the diploid group with genetic alterations had only 1 genetic change of 7 tested genes whereas 9 of 11 cases in the aneuploid group had multiple genetic alterations. Patients in the aneuploid group also showed a more unfavorable prognosis than patients in the diploid group. CONCLUSIONS: Based on the findings of the current study, flow cytometric DNA analysis is considered to be useful for both detecting multiple genetic alterations and predicting the prognosis of patients with carcinoma of the esophagus.     

Flow cytometric DNA analysis of interleukin-2 responsive renal cell carcinoma

Adoptive immunotherapy using interleukin-2 (IL-2) based therapy can result in marked tumor regression in some patients with metastatic renal cell carcinoma. DNA flow cytometry has not been previously studied as a predictor of outcome of this therapy. Archival paraffin embedded tumors were studied in 23 IL-2 treated patients with metastatic renal cell carcinoma. Eleven patients were complete responders (CR) and 12 were nonresponders (NR). In the CR group, 4/11 (40%) were diploid and 7/11 (60%) were aneuploid. In the NR group, 9/12 (75%) were diploid and 3/12 (25%) were aneuploid. Although there was a trend that patients with an aneuploid DNA pattern were more likely to undergo a complete response, ploidy pattern alone was not significantly predictive of response (p² = 0.10, Fischer's exact test). When combining ploidy pattern with other variables that were predictive for complete response, such as good performance status and a higher pretreatment weight, prediction of complete response was not improved by including ploidy. This preliminary report suggests that DNA ploidy does not appear to provide any additional information concerning responsiveness to IL-2 based immunotherapy beyond that obtained by performance status and pretreatment weight in this patient population. © 1993 Wiley-Liss, Inc.     

Comparative data on cytophotometric DNA in malignant lesions of the esophagus in the Chinese and Japanese

Cell DNA content was microspectrophotometrically determined in tissues of advanced esophageal carcinoma of 50 Chinese and 82 Japanese subjects. DNA distribution patterns were classified into Types I, II, III, and IV, according to the degree of dispersion and the peak value on the DNA histogram. The proportions of high ploidy (Types III and IV) in Chinese and Japanese patients were 68% and 81.7%, respectively. Overall 5-year survival rates of the Chinese and Japanese were 25.3% and 19.8%, respectively. Five-year survival rates of patients with Types II, III and IV were 45.7%, 23.8% and 0% in Chinese patients and 57.1%, 16.1%, and 0% in Japanese patients, respectively. Thus, differences in nationality were not related to the prognosis. The incidences of high ploidy group in those with an advanced esophageal carcinoma were high and were associated with a poor prognosis in both races. DNA distribution pattern of esophageal carcinoma reflected the outcome and malignant potential in the Chinese and the Japanese.     

食管癌渗疗71例近期疗效观察

采用食管渗疗器,治疗中,晚期食管癌71例。用高浓度5-Fu,食管腔内局部渗透给药。CR PR=66.2％,为Selawry报告静脉给药疗效的9.45倍。平均生存期9个月以上。渗疗前后检查对比,未见毒副反应。操作简单,适应症广,为治疗中、晚期食管癌创一新路。     

Prognostic value of DNA flow cytometry in the locally recurrent, conservatively treated breast cancer patient.

PURPOSE: This study attempted to determine the prognostic value of DNA flow cytometry in the treatment of patients with locally recurrent, conservatively treated breast cancer. METHODS AND MATERIALS: Of 433 patients with clinical stage I and II breast cancer treated with conservative surgery and radiotherapy at Yale-New Haven Hospital before January 1985, 50 patients experienced an ipsilateral breast relapse as a first site of treatment failure. Using standard flow-cytometric techniques, DNA ploidy, DNA index, and S-phase fraction (SPF) were measured for 38 of the 50 (76%) paraffin-embedded specimens available for analysis. RESULTS: At a median postrecurrence follow-up of 5.8 years, the 5-year and disease-free survival rates following ipsilateral breast treatment failure were 48% and 54%, respectively. Sixty-three percent of the recurrent tumors were DNA diploid and 37% were aneuploid. Both DNA ploidy and SPF were statistically significant prognostic indicators for 5-year survival and disease-free survival after local recurrence. The 5-year survival rate of the DNA diploid population was 64%, compared with 15% in the aneuploid population (P < .02). Patients with low SPF (< 12%) experienced an 83% 5-year survival rate, compared with a 24% 5-year survival rate in patients with high SPF (> or = 12%) (P < .03). Ploidy and SPF were combined to define the categories of favorable (diploid, low SPF) and unfavorable (diploid, high SPF or any aneuploid subgroups). Patients in the favorable category experienced an 89% 5-year postrecurrence survival rate and a 100% disease-free survival rate, whereas patients in the unfavorable category had a 24% 5-year survival rate and a 32% disease-free survival rate (P < .01). The flow cytometry as a factor correlated with other clinical parameters previously shown to be of prognostic significance in this patient population. In a multivariate analysis, flow cytometry was a statistically significant and independent prognostic factor for disease-free survival following local recurrence. CONCLUSIONS: DNA ploidy and SPF as measured by currently available flow-cytometric techniques show promise as a tool in determining prognosis for the patient with locally recurrent breast cancer. Implications of these findings with respect to issues of adjuvant systemic therapy at the time of local recurrence are discussed.     

肝癌患者癌旁组织DNA倍体,SPF,AFP和病理分级同步检测的临床意义

为探讨肝癌癌旁组织ＤＮＡ倍体、Ｓ期细胞比率（ＳＰＦ）、甲胎蛋白（ＡＦＰ）和病理分级等指标与患者肿瘤恶性度及预后的关系。对４２例肝癌患者癌旁组织倍体和ＳＰＦ、血清ＡＦＰ及肿瘤病理分级进行同步检测。结果显示患者癌旁组织异倍体检出率为５９．５％。癌旁组织倍体、ＳＰＦ、ＡＦＰ和病理分级之间均密切相关。根据患者对４项指标反应的不同分为预后不同的５级。这样，从Ⅰ级至Ⅴ级患者肿瘤恶性度越来越高，预后越来越差。其５ａ生存率和生存期分别为１００％、８５．７％、５５．６％、４４．４％、０和７５．９个月、６５．１个月、４７．４个月、４４．２个月、８７个月。认为肝癌癌旁组织ＤＮＡ倍体、ＳＰＦ、ＡＦＰ和病理分级等指标综合判断肿瘤恶性度和预后在临床上有重要意义     

Malignant potentiality of squamous cell carcinoma of the esophagus predictable by DNA analysis

Cell nuclear deoxyribonucleic acid (DNA) content was microspectrophotometrically determined in biopsy specimens from 75 patients with squamous cell carcinoma of the esophagus. The relationships among DNA distribution patterns, pathohistologic features, and prognosis were investigated. In patients with a high hyperploid DNA content (type IV), there was a high frequency of lymph node metastasis and lymphatic invasion, as compared with those exhibiting the near diploid DNA content (type II). In the type IV group, 22 of 23 patients died within 2 years, whereas patients with type II had a good clinical course and the 5-year survival rate was 60%. The DNA distribution pattern, determined by a multivariate Cox model analysis, was one of independent and significant prognostic variables. As these findings suggest that the DNA distribution pattern reflects the malignant potentiality of the tumor, the preoperative determinations of the DNA pattern in biopsy specimens of the esophageal carcinoma should provide a valuable parameter for predicting the prognosis.     

Flow cytometric analysis of nuclear DNA content in advanced gastric cancer and its relationship with prognosis

Cell nuclear DNA content was determined by flow cytometric analysis in 270 patients with deeply infiltrating (beyond the submucosa) cancer, so-called advanced gastric cancer. Aneuploidy was observed in 150 cases (55.6%). Multivariate analysis showed that the DNA ploidy pattern was the third significant prognostic factor behind peritoneal dissemination and liver metastasis. The 5-year survival rate of diploid patients (62.9%) was significantly higher than that of aneuploid patients (22.7%) (P less than 0.01). This trend was most clear in patients with Stage III and IV tumors. Among aneuploid cases the high DNA index group indicated a worse prognosis than the low DNA index group. It was thus assumed that the DNA ploidy pattern was a useful prognostic indicator of advanced gastric cancer.     

Cisplatin and bleomycin in the treatment of esophageal carcinoma. A final report

During the period from September, 1976 to June, 1979, 70 patients with locoregional or extensive epidermoid carcinoma of the esophagus were treated with the two-drug combination of cisplatin and bleomycin (DB). For the 43 patients with locoregional disease (LRD), DB was used prior to surgery and/or radiation therapy; it was the primary treatment for 27 patients with extensive disease (ED). The major objective response rates [complete remission (CR) and partial remission (PR)] to DB for the LRD and ED groups were 14% and 17%, respectively, for an overall response rate of 15%. For the LRD group, the minimum follow-up was 42 months; four patients (10%) remain alive and free of disease. The median survival of 34 patients treated with DB preoperatively was 10 months, which did not differ significantly from that of a historic control group receiving preoperative radiation therapy. The median duration of response for ED patients was 6 months, and the median survival for the entire ED group was 4 months. DB alone had only modest activity in epidermoid carcinoma of the esophagus.