Compartmental resection for subfascial extremity soft tissue sarcoma and quality of life in long-term survivors.

The surgical management of soft tissue sarcoma has changed over the past years, resulting in an interdisciplinary multimodal approach and limb-preserving treatment modalities. From 464 consecutive patients with a soft tissue sarcoma (STS) of an extremity, a compartmental resection was performed in 82 patients, usually for primary subfascial large tumors. Postoperative quality of life was evaluated using the EORTC Score C30. In our study population, 52% of STS was poorly differentiated, 32% moderately, and 16% well differentiated. Survival proved to be dependent on tumor grade and tumor biology, but not on tumor size. The overall survival rate was 81.5%, 71.9%, and 58.3% after 2, 3, and 5 years, respectively. Leiomyosarcoma (39%) and malignant fibrous histiocytoma (42%) are associated with poor 5-year survival rate compared to liposarcoma (82%). Metastases were observed in 33% of T1 and 43% of T2 tumors corresponding to 51% with G3 tumors, 52% with G2 and 23% with G1 tumors. We found a decreased quality of life score in our patients in all dimensions compared to a normal population. Despite the elevated risk of a functional deficit, compartmental resection reduces the risk of local recurrence comparable to the recurrence rates after the most radical surgery limb amputation.

Superficial soft tissue sarcomas of the extremities and trunk.

BACKGROUND: Superficial soft tissue sarcomas (sSTS) are an important and frequent subtype of soft tissue sarcoma (STS). A wider knowledge of this tumor type may lead to better strategies in tumor therapy. METHODS: An institutional review was performed on all patients with primary sSTS of the extremities and trunk operated on between 1990 and 2003. RESULTS: The medical records of 108 patients with sSTS were analyzed. The local recurrence rate was 11% after a median of 25 (mean 42) months. Metastases occurred in 21 patients (19%), and 79 patients lived without evidence of disease after a mean follow-up of 112 +/- 42 months. Mean survival time was 89 months at a cumulative 5-year survival rate of 85%. R0 resection significantly enhanced cumulative survival (p = .001), as did patient age < 60 years (p = .002), tumor grading G1 and G2 compared to G3 (p = .004), absence of positive lymph nodes (p = .018), and no occurrence of metastases (p = .001). Tumor size < or = 5 cm reduced the local recurrence rate significantly (p = .044). Significant multivariate risk factors for metastases were age > or = 60 years (p = .016) and tumor grade G3 (p = .021). CONCLUSIONS: Patients with sSTS who are > or = 60 years of age or who have G3 tumors have a high risk of distant metastases. Patients with T2 tumors have an elevated risk for local recurrence. Certainly all patients with sSTS should be in a tight after-care program to allow early diagnosis of local recurrence or distant metastases. Age < 60 years, tumor grade G1/2, no positive regional lymph nodes (N0), and a R0 resection are significant prognostic factors for survival.

Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer.

BACKGROUND: The chemokine and bone marrow-homing receptor CXCR4 has been implicated in metastatic dissemination of various cancers. We investigated CXCR4 expression in esophageal cancer specimens and its association with survival, lymph node microinvolvement, and bone marrow micrometastasis. METHODS: We analyzed frozen tumor specimens from 136 patients with completely resected esophageal cancer for CXCR4 expression by immunohistochemistry. Lymph node microinvolvement and bone marrow micrometastasis were assessed by immunohistochemistry with monoclonal antibodies Ber-EP4 (against epithelial cell adhesion molecule) and pancytokeratin A45-B/B3 (against several cytokeratins), respectively. Associations between CXCR4 expression and clinicopathologic features, including tumor stage, histologic grade, lymph node metastasis and microinvolvement, bone marrow micrometastasis, and survival, were investigated with Fisher's test, log-rank test, and Cox multivariable analysis. All statistical tests were two-sided. RESULTS: CXCR4 protein was expressed in 75 (55%) of 136 esophageal tumors examined. CXCR4 expression was statistically significantly associated with reduced median overall and disease-specific survival, compared with CXCR4 nonexpression (P < .001; log-rank test). The median overall survival of patients with CXCR4-positive tumors was 20 months and with CXCR4-negative tumors, 76 months (difference = 56 months, 95% confidence interval [CI] = 4 to 108 months; P < .001). The median disease-specific survival of patients with CXCR4-positive tumors was 25 months and with CXCR4-negative tumors was 97 months (difference = 72 months, 95% CI = 34 to 110 months; P < .001). CXCR4 expression was statistically significantly associated with increased lymph node microinvolvement (P < .001) and with increased bone marrow micrometastasis (P < .001). In multivariable analysis, CXCR4 expression, compared with its nonexpression, was identified as the independent variable that was most strongly associated with reduced disease-specific survival (relative risk [RR] of death = 2.03, 95% CI = 1.20 to 3.41; P = .008) and overall survival (RR of death = 2.18, 95% CI = 1.33 to 3.59; P = .002). CONCLUSION: CXCR4 expression was associated with poor clinical outcome in esophageal cancer patients. CXCR4 may have a role in early metastatic spread because its expression was associated with micrometastases to both the lymph nodes and bone marrow. Thus, CXCR4 should be explored further as a target for adjuvant therapy for micrometastatic disease.

CD44s expression is associated with improved survival in soft tissue sarcoma.

Expression of CD44 has been identified as a prognostic factor in several malignant diseases. Few studies have correlated CD44 expression in soft tissue sarcoma with subsequent tumor progression or recurrence. We sought to investigate the clinical significance of CD44s (standard) in adult soft tissue sarcoma (STS). Tumor specimens of 62 patients with STS were evaluated by immunohistochemistry for CD44s expression. The primary outcome measures were survival and local recurrence. Of 62 analyzed specimens, 49 tumors were CD44s-positive compared to 13 CD44s-negative tumors. Kaplan-Meier survival analysis indicated significantly better survival among patients whose tumor was CD44s-positive (p=0.015). CD44s expression (hazard ratio, 3.1; 95% confidence interval, 1.5 to 7.0), tumor size (hazard ratio, 11.7; 95% confidence interval, 1.8 to 322) and resection quality (R1 vs. R0: hazard ratio, 8.7; 95% confidence interval, 3.1 to 24.5) were independent predictors of survival in multivariate analysis. CD44s expression correlates with prognosis of soft tissue sarcomas and therefore may have a pathogenetic role in tumor progression. Our results suggest that expression of CD44s in primary STS provides value regarding the progression of STS and, therefore, could be useful in selecting patients for adjuvant treatment.

Biological and molecular characterization of a new human ampullary cancer cell line.

BACKGROUND: Ampullary carcinoma of the pancreas accounts for 5% of all gastrointestinal malignancies in humans. Only a very few cell lines of this carcinoma have been established. PATIENTS AND METHODS: Tumor cells isolated from a surgically resected ampullary carcinoma were put into culture. The cultured cells were characterized for their biological, immunological and molecular properties including in vitra and in viva cell kinetics, karyotype, expression of tumor markers and lysis by autologous cytotoxic T-lymphocytes. RESULTS: An ampullary cancer cell line, designated UKEAC-99, was established. It proliferates as a monolayer with a doubling-time of 29 hours. The cytological features of the cultured and of the xenografted cells from SCID mice were similar to those of the primary tumor. UKEAC-99 cells were lysed by autologous cytotoxic T-lymphocytes in a HLA-class I restricted fashion. Hybridization of tumor mRNA to a dedicated DNA-chip revealed overexpression of several genes involved in tumor progression such as L6, Matrilysin and Vimentin. Tumor suppressor genes and apoptosis-associated genes like p73 or IL1 alpha are expressed at a low level. CONCLUSION: We established a new ampullary carcinoma cell line, which is rare and may contribute to our understanding of the biological behavior of ampullary carcinoma. The lysis by autologous cytotoxic T-lymphocytes and possibly shared antigens with other pancreatic cancers may help to identify tumor-associated/tumor-specific antigens. The detailed analysis of gene expression allows researchers new insights into ampullary cancer that can be exploited in future in vitro and in vivo models.