Significant Predictors Of Poor Survival Research Articles

Factors Associated with Survival after Surgical Resection in Chinese Patients with Ductal Adenocarcinoma of the Pancreatic Head

Objectives: The aim of this cohort study was to investigate clinical outcome and prognostic factors after resection for ductal adenocarcinoma of the pancreatic head. Methods: 134 patients with pancreatic cancer undergoing curative resection (R0) between 1997 and 2002 were included in this study. Univariate and multivariate analyses were performed to examine factors affecting clinical outcome and recurrence. Results: Surgical procedures consisted of 58 (43.3%) extended pancreaticoduodenectomies, 47 (35.1%) pancreaticoduodenectomies and 29 (21.6%) pylorus-preserving pancreaticoduodenectomies. Results showed that 81.3% patients had a recurrence during the study period, mainly retroperitoneal recurrence in combination with distant metastasis (53.7%). The median survival time was 24.67 months. The 1-, 3- and 5-year overall disease-free survival rates for the study population were 52, 23 and 19%, respectively. Conclusions: The results from proportional hazard analysis suggest that preoperative abdominal and/or back pain, tumor size >2 cm, lymph node involvement and vascular invasion were significant predictors for poor survival.

Functional Outcome 3 Months after Stroke Predicts Long-Term Survival

Background: When reporting stroke survival and prognostic factors with a possible effect on outcome, the starting point for the observation of a clinical cohort usually is the onset of stroke or the acute admission of a patient. Thus, acute and early mortality inflict prognosis on long-term outcome. In order to give a more robust analysis of long-term survival after the acute period we chose to start our observation with 3-month survivors. Methods: We used data from Riks-Stroke, the Swedish quality register for stroke care, together with survival information from the Swedish population register to explore the influence of disability level 3 months after stroke on long-term survival. The main analysis included 15,959 stroke patients, registered during 2001–2002, who had been independent in primary activities of daily living before stroke, had suffered an ischaemic or a haemorrhagic stroke and reported no previous stroke. Results: Impaired functional outcome after stroke was an independent predictor of poor survival. Patients with modified Rankin scale (mRS) grades 3, 4 and 5 had hazard ratios of 1.7, 2.5 and 3.8, respectively, as compared with patients with lower mRS grades. In addition to high mRS, male sex, high age, diabetes, smoking, hypertension therapy at stroke onset, atrial fibrillation and depressed mood were also recognized as significant predictors of poor survival using a multiple Cox regression model. Conclusion: The influence of disability on survival is stronger than that of several other well-known prognostic factors. This finding indicates that any intervention in the acute phase that may improve functional status at 3 months will also have favourable secondary effects on survival in the long term.

Platelet count is an IPSS‐independent risk factor predicting survival in refractory anaemia with ringed sideroblasts

Platelet count is an IPSS‐independent risk factor predicting survival in refractory anaemia with ringed sideroblasts

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Using laser-captured microdissection and a real-time RT–PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55–3.67)), high DPD (HR: 2.04 (1.37–3.02)), low EGFR (HR: 0.34 (0.20–0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001–1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

Serum Interleukin-6 Level but not Genotype Predicts Survival after Resection in Stages II and III Gastric Carcinoma

It has been suggested that interleukin-6 (IL-6) is a prognostic indicator for survival in patients with gastric carcinoma, but this has not been proved using survival analysis. In Asians, the -634G allele is associated with increased IL-6 production. The objective of this study was to evaluate the association between serum IL-6 levels, -634G/C polymorphism, and overall survival after resection for gastric carcinoma. A total of 155 consecutive patients with gastric carcinoma were evaluated. Serum IL-6 levels were analyzed using an enzyme-linked immunoabsorbent assay. Genotype was determined by PCR and restriction fragment length polymorphism. Serum levels and survival were correlated with genotype and clinicopathologic factors. Age and stage, but not -634G/C genotype, were associated with serum IL-6 levels. The median survival for patients with stage II or stage III gastric carcinoma was 1,418 days in patients with low (< or =13 pg/mL) versus 618 days in patients with high (>13 pg/mL) serum IL-6 levels (P = 0.038). Results of a multivariate analysis showed that serum IL-6 level of >13 pg/mL was a significant predictor of poor survival (hazard ratio, 1.77; 95% confidence interval, 1.07-2.92; P = 0.026). Serum IL-6 level of >13 pg/mL correlates with tumor progression and is an independent predictor of poor survival after resection. In patients with stage II and III gastric carcinoma, serum IL-6 level is more effective than stage as a prognostic indicator. By measuring IL-6, these patients can be divided into two groups with significant differences in survival. The -634G/C polymorphism is not associated with serum IL-6 level or survival.

Postoperative External Beam Radiotherapy for Retroperitoneal Soft Tissue Sarcoma

Purpose: To evaluate the clinical outcomes and prognostic factors in retroperitoneal soft tissue sarcomas treated by postoperative radiotherapy. Materials and Methods: The records of 23 patients with retroperitoneal soft tissue sarcomas, who underwent postoperative radiotherapy between 1985 and 2003, were analyzed. The median follow-up period was 77 months (range, 8∼240 months). A total of 21 patients presented with primary dise ase, and two patients presented with recurrent disease. Liposarcomas and leiomyosarcomas represented 78% of the diagnosed tu- mor cases. Moreover, 17 cases were of high grade (grade 2 or 3). The median tumor size was 13 cm (range, 3∼ 50 cm). Complete excision was achieved in 65% of patients. The median radiation dose was 50.4 Gy (range, 45.0 to 59.4 Gy), with conventional fractionation. Results : The 5-year overall, local recurrence-free, and distant metastasis-free survival rates were 68%, 58%, and 71%, respectively. Eleven patients experienced local recurrence, while 9 patients experienced distant metastasis. The most common site for distant metastasis was the liver. A univariate analysis revealed that adjacent organ invasion and age (>60 years) as the significant risk factors contributing to the prediction of poor overall survival. Moreover, multivariate analyses indicated that adjacent organ invasion remained sig- nificantly associated with a higher risk of death. In addition, patient age (>60 years) was the other identified risk factor for local recurrence by univariate and multivariate analyses. Except for one case of grade 3 diar- rhea, no patient suffered grade 3 or higher complications. Conclusion : Our results were comparable to previous reports in that adjacent organ invasion and patient age (>60 years) were significant predictors of poor survival and tumor recurrence, respectively.

17: Double Reduced Intensity Cord Blood Transplants in Adults

Umbilical cord blood is a useful stem cell source for patients without matched donors, but the low cell dose in individual cord blood units has limited success in adults. We treated 43 patients using a reduced intensity conditioning regimen of fludarabine 30 mg/m2/day Days –8 through –3 (total dose 180 mg/m2), melphalan 100 mg/m2 Day –2 and rabbit antithymocyte globulin 1.5 mg/kg Days –7, −5, −3, −1 (total dose 6 mg/kg). Cord blood units were a 4/6 or higher HLA A, B, DR allele match with the patient and each other and achieved a minimum precryopreservation cell dose of 3.7 × 10 (7) NC/kg. Twenty-one patients received GVHD prophylaxis with cyclosporine and mycophenolate mofetil and 22 patients received tacrolimus and sirolimus. Median age was 49 years and majority of patients had acute leukemia or relapsed lymphoma. The median days to neutrophil and platelet engraftment were 20 and 41 days respectively for the cyclosporine/MMF group and 21 days and 47 days for the tacrolimus/sirolimus patients. The incidence of acute GVHD Grades II-IV and chronic GVHD in the cyclosporine/MMF group was 40% and 34% respectively and 14% and 20% respectively for the tacrolimus/sirolimus patients. Transplant related mortality was 14% in both groups. Overall survival and disease free survival were 57% and 57% at 2 years respectively for the cyclosporine/MMF patients and 73% and 51% at one year for the tacrolimus/sirolimus patients. In a multivariate analysis, age greater than 50 was the only significant predictor of poorer survival. Chimerism studies revealed that one cord unit predominates in 73% of patients. Predictors of the predominant unit include first infusion and higher CD34 and nucleated cell counts. Double cord blood transplantation can be performed safely with this reduced intensity regimen; the graft vs leukemia effect is preserved despite a low rate of graft versus host disease.

Plasma EBV DNA and cell-free GAPDH DNA as prognostic factors of locally advanced nasopharyngeal carcinoma

6053 Background: Plasma cell-free nucleic acids have been investigated to be potential prognostic and predictive markers of treatment response, residual disease, and survival of cancer patients. However, these nucleic acids will be confounded by normal cell death, which might be caused by cancer-related inflammation, infection, or chemotherapy. Nasopharyngeal carcinoma is endemic in Taiwan, highly related to EBV infection. Plasma EBV DNA level has been suggested to be predictive of disease status and outcomes. We try to find out whether plasma EBV and cell-free glyceraldehydes-3-phosphate dehydrogenase DNA before definite treatment of locally advanced NPC predict tumor outcomes better. Methods: 144 stage IV (AJCC version 6) NPC patients received induction chemotherapy followed by concurrent chemoradiotherapy in National Taiwan University Hospital from 1998 to 1999. Pre-treatment blood samples were colleted for real-time quantitative polymerase chain reactions of EBV and GAPDH DNA. The results will be analyzed by SPSS version 13 to see if correlated with tumor extent, locoregional/distant failure, and overall survival. Results: Our patients were mainly composed of T4(97%) and N2(56%) patients. 23 % were in N3 stage. Plasma EBV and cell-free GAPDH DNA levels were not correlated with T stage. Plasma EBV DNA level was significantly correlated with N3 status(Mann-Whitney test p=0.021). After Cox regression model, only age (p=0.024) was a significant predictor of recurrence-free survival; N3 status(p=0.007) and positive plasma EBV DNA (p=0.002) predicted shorter metastasis-free survival. N3 status (p=0.031) and positive plasma EBV DNA (p=0.002) were significantly related to poor survival by log-rank test; whereas T4 lesions (p=0.524) and plasma cell-free GAPDH DNA level (p=0.182) were not. After multivariate Cox regression, positive plasma EBV DNA (hazard ratio 4.936 p=0.006) was the only significant predictor of poor survival. Conclusions: To use circulating DNA as prognostic marker, a specific one, such as EBV DNA, might be better than a non-specific one, like GAPDH DNA. This is important in the development of tumor markers for other solid tumors. No significant financial relationships to disclose.

GENETIC ABERRATIONS IN GLIOMATOSIS CEREBRI

Identifying the genetic alterations in gliomatosis cerebri (GC) may yield clinically useful prognostic markers and provide clues as to whether GC represents a distinct pathological entity or is an extreme form of diffusely infiltrative glioma. Clinical histories, treatment histories, magnetic resonance imaging, and pathological analysis of patients with GC treated at either the University of California San Francisco or the Mayo Clinic were reviewed. Degenerate oligonucleotide-primed polymerase chain reaction was performed on biopsy samples of GC. Comparative genomic hybridization was used to determine relative deoxyribonucleic acid copy number. We evaluated relationships of clinical and radiological treatment and comparative genomic hybridization data to survival after diagnosis with Cox regression analysis. Radiographic analysis and biopsy specimens were available for study in 29 patients (17 men, 12 women). Comparative genomic hybridization was successfully performed in 22 patients. Contrast enhancement was the most significant predictor of poor survival (P = 0.0026). Loss of chromosomes 13q and 10q and gains of 7q were also independent significant predictors of poor survival (P = 0.0032, 0.0335, and 0.0487, respectively). Patients treated with temozolomide or with radiation therapy had improved survival, but this effect did not reach statistical significance (P = 0.180 and 0.124, respectively). Chromosomal aberrations associated with aggressive astrocytomas are predictors of poor outcome in patients with GC. This suggests that GC may be an architectural variant of diffuse astrocytomas. The presence of these aberrations and the presence of any contrast enhancement on magnetic resonance imaging scans are possible stratifiers for patients with GC. Stratification of GC into higher- and lower-grade forms may be useful in tailoring treatments to patients with this disease.

Clinical Implications of Combined Portal Vein Resection as a Palliative Procedure in Patients Undergoing Pancreaticoduodenectomy for Pancreatic Head Carcinoma

The clinical implications of combined portal vein resections are controversial. One-hundred and forty-nine consecutive patients underwent macroscopically curative pancreatectomies for pancreatic head carcinoma between January 1, 1996 and December 31, 2004. Portal vein resection was performed in 86 patients (58%). Data on surgical mortality, morbidity, perioperative outcome, pathological factors, initial recurrence site, and survival were retrospectively compared between the patients with and without portal vein resection. The incidence of postoperative pancreatic fistula was lower among patients who underwent portal vein resection. The median survival period was 14 months for the portal vein resection group and 35 months for the non-portal vein resection group, respectively. Combined portal vein resection was a significant predictor of poor survival using a multivariate analysis. Portal vein resection was strongly associated with larger tumor size, the degree of retropancreatic tissue invasion, the presence of extrapancreatic nerve plexus invasion, lymph node metastases, and positive cancer infiltration at the surgical margins. Portal vein resection at the time of pancreaticoduodenectomy can be safely performed. However, most of patients requiring portal vein resection do not achieve a potentially curative resection or a favorable survival term. As a result, the aggressive application and the strict selection of portal vein resection might reduce the incidence of positive surgical margins, enabling long-term survival in patients who do not require portal vein resection.

Significance of necrosis in grading of anaplastic oligodendroglial tumors: A clinicopathological and genetic study of 916 high-grade gliomas

1502 Background: High-grade gliomas (HGG, WHO grades III-IV) are morphologically and genetically diverse, with survivals ranging from months to decades. Although WHO 2000 grading criteria are well established for pure astrocytomas [anaplastic astrocytoma (AA) and glioblastoma (GBM)], those for oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and oligodendroglioma (AO)] remain subjective, there being a debate regarding the existence of a grade IV variant based on the finding of necrosis, particularly with pseudopalisading (PPN). Methods: Overall survival of 916 adult (&gt;20 yr) patients diagnosed between 1990 and 2005 with supratentorial HGG (77 AA, 481 GBM, 183 AOA, 175 AO) was analyzed by uni- (log-rank) and multivariate (Cox proportional hazards) models for significance of the following factors: microvascular proliferation, necrosis, patient age, surgery (stereotactic vs. open), location, primary vs. secondary tumor, year of diagnosis, and chromosome 1p and 19q losses by fluorescence in situ hybridization. Results: Necrosis was a statistically significant predictor of poor survival on multivariate analyses in AOA (P=0.035), but not in AO (log-rank P=0.048, Cox P=0.9), while PPN showed a trend towards significance on multivariate analysis only in AOA (P=0.096). Other independent predictors on multivariate analysis included age, grade, surgery type, and year of diagnosis for AA/GBM and age, primary tumor, and 1p/19q codeletion for both AOA and AO (P&lt;0.05). Median survival for AOA patients whose tumors featured necrosis (20.7 mo) was significantly worse than their counterparts lacking necrosis (&gt;104 mo); survival of the latter was more similar to that of AO (83.5 mo), whereas in the former it was better than GBM (10.5 mo) (log-rank P&lt;0.0001). Conclusions: Stratification of oligoastrocytomas, but not of pure oligodendrogliomas, into grades III (AOA) and IV (GBM with oligodendroglial features) on the basis of necrosis is prognostically justified and is more accurate than the current approach of using a single anaplastic grade. These data provide impetus for the modification of present WHO criteria. No significant financial relationships to disclose.

Effect of Donor Age on Long-Term Survival Following Cardiac Transplantation

The current shortage of donor hearts has forced the criteria of organ procurement to be extended, leading to increased use of older donor hearts to bridge the gap between demand and availability. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital - Columbia University between 1992 and 2002. Patients were divided into two groups; donor age <40 years (Group A, n = 600) and donor age > or =40 years (Group B, n = 264). Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. These findings suggest that increased donor age is an independent predictor of long-term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis.

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS)

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian-German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis

Intracellular signals along the epidermal growth factor receptor (EGFR)–Akt–nuclear factor-kappa B (NF-κB) pathway have been associated with carcinogenesis in various malignant neoplasms. This investigation was to evaluate the expression of EGFR, phosphorylated(p)-Akt and p-NF-κB and correlate them with clinical outcomes in patients with squamous cell carcinoma of the tonsil. A total of 45 patients with squamous cell carcinoma of the tonsil were studied by immunohistochemistry to evaluate the expression levels of EGFR, p-Akt and p-NF-κB. Results for squamous cell carcinoma of the tonsil were compared with those for associated high-grade dysplasia and adjacent normal appearing epithelium, when present. In addition, tonsillar epithelium from non-neoplastic specimens of age-matched patients also was stained for the same markers. High-grade dysplasia and squamous cell carcinoma of the tonsil demonstrated a similar pattern of expression, which differed from the pattern seen in the adjacent normal epithelium and tonsillar epithelium from normal controls (an overexpression for each of these three protein analytes in high-grade dysplasia and squamous cell carcinoma of the tonsil as demonstrated by immunohistochemistry). When markers from squamous cell carcinoma of the tonsil were correlated with survival status, only increasing levels of p-NF-κB immunoreactivity (a relative overexpression) were statistically significant predictors of poor survival. No markers in squamous cell carcinoma of the tonsil were significantly related to rate of recurrence. When analyzing marker scores from tissue with high-grade dysplasia, relative overexpressions of both p-Akt and p-NF-κB were significantly related to poor survival. Additionally, increasing levels of p-NF-κB immunopositivity from tissue with high-grade dysplasia were also significantly related to rate of recurrence. In summary, p-NF-κB, overexpressed in high-grade dysplasia and squamous cell carcinoma of the tonsil, is associated with worse prognosis in terms of high recurrence and poor survival, respectively. This significant finding in patients with squamous cell carcinoma of the tonsil, in combination with previous animal and in vitro studies, suggests that p-NF-κB represents a potential therapeutic target in head and neck squamous cell carcinoma.

African Americans with hepatocellular carcinoma have worse survival than Caucasians: A tumor registry study

6062 Background: SEER data suggest an increasing incidence of hepatocellular carcinoma (HCC) in the US, and overall 5-year survival is less than 5%. Which subgroups of patients with HCC have the poorest prognosis is not known. Methods: To determine what factors affect survival of HCC patients and if survival has changed significantly in the last three decades, we performed a retrospective analysis of 193 consecutive patients diagnosed from 1971–2000 with HCC, identified from a hospital tumor registry. Cox regression analysis was performed to identify demographic variables prognostic for survival. Results: The study cohort comprised 193 patients, (106 Caucasians, 84 African American (AA), and 3 other). There were 73 females and 120 males. The median age at diagnosis for the cohort was 67 years (range 13–90 years). Median survival for the entire cohort was 77 days. Patients were divided into 3 groups based on decade of diagnosis. Group 1 included 47 patients diagnosed from 1971–80, group 2 had 63 patients diagnosed 1981–90, and group 3 had 83 patients diagnosed 1991–2000. Overall survival did not change over the three decades (p = 0.94) for the entire cohort and for both races. In a multivariate analysis, AA race was significantly predictive of poorer survival (HR 1.45, 95% CI 1.07–1.96, p = 0.017), but age, gender and decade of diagnosis were not independent risk factors. AA patients had a significantly lower overall survival when compared to their Caucasian counterparts only in the last decade of analysis (p = 0.026) with a trend towards significance in the second decade (p = 0.083). Conclusions: We conclude that survival for HCC patients has remained low over the last three decades, and AA race is a significant predictor of poor survival. More studies are needed to determine what biological factors lead to the poorer survival for AA patients. No significant financial relationships to disclose.

Critical Appraisal of the Clinical and Pathologic Predictors of Survival After Resection of Large Hepatocellular Carcinoma

A subset of patients with hepatocellular carcinoma (HCC) with a diameter of 10 cm or larger may benefit from hepatic resection. Retrospective study of a multi-institutional database. Five major hepatobiliary centers. We identified 300 patients who underwent hepatic resection for HCC 10 cm or larger. Clinical and pathologic data were collected, and prognostic factors were evaluated by univariate and multivariate analyses. Patient survival was stratified according to a clinical scoring system and pathologic T classification. The perioperative mortality rate was 5%. At a median follow-up of 32 months, the median survival was 20.3 months, and the 5-year actuarial survival rate was 27%. Four clinical factors-alpha-fetoprotein of 1000 ng/mL or higher, multiple tumor nodules, the presence of major vascular invasion, and the presence of severe fibrosis-were significant predictors of poor survival (all P<.05). Patients were assigned a clinical score according to the following risk factors: 1, no factor; 2, one or two factors; or 3, three or four factors. On the basis of the clinical score, patients could be stratified into only 2 distinct prognostic groups: no factor (score of 1) vs 1 or more factors (score of 2 or 3) (P<.001). In contrast, when patients were stratified according to pathologic T classification, 3 distinct groups were identified: T1 vs T2 vs T3 and T4 combined (P<.001). Fifty-six percent of the patients with a clinical score of 2 and 20% of patients with a clinical score of 3 actually had T1 or T2 disease on pathologic examination. Patients with large HCCs should be considered for liver resection as this treatment is associated with a 5-year survival rate exceeding 25%. Clinical predictors should not be used to exclude patients from surgical resection because these factors do not reliably predict outcome.

Clinicopathologic significance of dysadherin expression in cutaneous malignant melanoma

The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and down-regulates E-cadherin. Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors. Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001). Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma.

Prognostic Significance of Dysadherin Expression in Tongue Cancer: Immunohistochemical Analysis of 91 Cases

The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently we have reported a novel cell membrane glycoprotein, dysadherin, which has an anti-cell-cell adhesion function and downregulates E-cadherin. Expressions of dysadherin and E-cadherin were investigated immunohistochemically in 91 patients with squamous cell carcinoma of the tongue to determine the correlation between the 2 molecules and their associations with the clinicopathologic features of the tumors and with patient survival. Dysadherin was expressed at the cell membranes of many cancer cells. Twenty-five percent of the tumors showed dysadherin immunopositivity in more than 50% of the cancer cells. Sixty-nine percent of the tumors showed reduced E-cadherin immunopositivity. There was an inverse correlation between dysadherin expression and E-cadherin expression (P = 0.0001). Increased dysadherin expression was significantly correlated with an infiltrative type of growth pattern (P = 0.001), high tumor-node-metastasis (TNM) stage (P = 0.024), and poor patient survival (P = 0.003). After adjusting for growth pattern, TNM stage, and other clinicopathologic features, increased dysadherin expression and reduced E-cadherin expression were both significant predictors of poor survival (P = 0.0006). Increased dysadherin expression is a significant indicator of poor prognosis in patients with squamous cell carcinoma of the tongue.

Outcome of Patients with Esophageal Carcinoma and Suspicious Celiac Lymph Nodes as Determined by Endoscopic Ultrasonography

The management of patients with esophageal cancer with malignant celiac lymph nodes (CLNs) is controversial. In this study we evaluated the management and survival of patients with positive CLN findings on endoscopic ultrasonography (EUS) and compared the outcome in surgically treated patients with that of nonsurgically treated patients. The EUS database of the Academic Medical Center was retrospectively searched for patients with esophageal carcinoma and EUS-positive CLN. Follow-up comprised the review of medical charts and contact with general practitioners. From 1993 through 2000, 78 patients with esophageal carcinoma and suspicious CLN were eligible for inclusion in this study. The median survival of patients with CLN size < 2 cm was 13.5 months vs. 7.0 months for patients with CLN size >2 cm ( P = 0.01). In a multivariate model, CLN size was the only predictive factor for poor patient survival. Of the 78 study patients, 13 underwent a surgical resection and 65 received nonsurgical treatment. The surgical group was significantly younger and all patients in this group had CLN size < 2 cm. The median survival for the surgical group was 13.7 months vs. 13.5 months for the nonsurgical group with CLN size < 2 cm ( P = 0.63). In this retrospective study, CLN size was a significant predictor for poor survival. The surgically treated patients had a medium-term survival similar to that of nonsurgically treated patients with a CLN size < 2 cm. These findings underline the prognostic value of CLN size in patients with esophageal carcinoma.

Prognostic factors in early stage head and neck squamous cell carcinoma (HNSCC) patients in a prospective clinical trial

5515 Background: HNSCC is the 5th most common cancer in the United States. A majority abuse tobacco which leads to higher relapse rates and second primary tumors (SPT). Methods: We reported results of a randomized chemoprevention study (FRK ASCO 2003) in which pts received isotretinoin or placebo. This analysis focuses on the placebo group and prognostic characteristics related to prior therapy, site of disease, stage, and smoking status. Results: From 1991 to 1999, 600 pts were enrolled into the placebo arm: stage I (n=389), II (211); primary tumor of larynx (L; 343), oral cavity (OC; 187), pharynx (P; 70); prior therapy of radiation (RT; 353), surgery (S; 158), both (86); and smoking status of current (220), former (296), never (84). The median follow-up is 6 years and 5-year survival is 0.83 (0.80, 0.87). We compared the above pts in statistical models to identify prognostic markers, which may impact recurrence, smoking-related (sm) SPT development, disease-free (DFS), and overall survival (OS). Smoking status was found to be associated with site: OC primaries with more nonsmokers, L with more former smokers, and P with more current smokers. Site of disease was associated with stage as more L pts presented in stage I and P stage II. Treatment related with site of disease: L received more RT, OC received more S, and P received more of both. Treatment also related with stage: more single therapy for stage I and combination for II.Significant observations included worse recurrence-free and sm-DFS for OC as compared to L (P=0.0003 and 0.007, respectively), worse recurrence-free survival in pts with prior RT as compared to S (P=0.007) which was also marginally significant for survival (P=0.06); and higher sm-SPT survival for P primaries as compared to L (p=0.02). After adjusting by stage, site, and smoking status, sm-SPT survival and OS for current smokers was worse (p=0.04, p=0.008). Conclusion: Smoking status did not predict recurrence but current smoking status was the most significant predictor for poor survival. Further studies are needed to investigate the interaction between smoking and primary treatment modality early stage HNSCC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca Pfizer Pfizer AstraZeneca; Aventis Trial was funded by NCI-PO1 grant; this is a subset analysis of the trial