Date Of Initial Diagnosis Research Articles

Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence following multi‐modality therapy: A report from the Children's Oncology Group

The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%. To evaluate prognostic factors for these patients we studied patients initially treated on the multi-institutional study INT0091. Two hundred sixty-two patients experienced disease recurrence. The median time to first recurrence was 1.3 years (0-7.4 years), 1.4 years (0-7.4 years) for patients with initially localized disease and 1 year (0-6 years) for patients with initially metastatic disease. Time to first recurrence from date of initial diagnosis was a predictor of post-recurrence survival (P < 0.0001). Twenty-one percent of patients, with recurrent or progressive disease >or=2 years from initial diagnosis, had an estimated 5-year survival of 30% (vs. 7% estimated 5-year survival with an earlier recurrence). No statistical difference was detected between patients whose disease recurred <1 year and between 1 and 2 years from initial diagnosis. A stepwise relative risk model and backwards stepwise regression was used to explore factors significantly associated with risk for post-recurrence death. Significant risk factors for death after recurrence included recurrence at combined local and distant sites, elevated LDH at initial diagnosis and initial recurrence less than 2 years after diagnosis. Isolated pulmonary recurrence was not predictive of survival after recurrence. Patients with a longer disease control interval represent the subset of patients most likely to survive following recurrence of EWS. All patients with recurrence would benefit from collaborative trials to investigate new therapeutic options.

Treatment of stage I breast cancer (T1N0M0): A long-term follow-up study

11509 Background: Most cases of breast cancer are diagnosed at early stage of disease, therefore treatment is oriented to increase the relapse-free survival (RFS) and overall survival (OS). The prognosis, in comparison to other malignancies, has improved in the last decades as a result of mammographic screening. The objective of this study was to evaluate the incidence of local and distant recurrence, RFS and OS in women with early breast cancer within our institution. Methods: Between January 1978 and December 2006, 251 women with T1N0M0 (AJCC) breast cancer were identified. Tumor size was determined from the pathology report. RFS was analyzed from the date of initial diagnosis to the date of local or distant recurrence. OS was estimated from the date of initial diagnosis to the last follow-up or date of death. Multivariate regression analyses were carried out using the proportional hazard model proposed by Cox. RFS and OS were evaluated by the product-limit method of Kaplan and Meier, and differences between curves were assessed by means of the log-rank test. Results: The median age at the time of diagnosis was 52 years (28–84). Conservative surgery was performed in 92% of patients (pts) and 98% underwent nodal dissection. The median number of nodes examined was 18.5. ER was positive in 74% of pts and PR was positive in 66%. Adjuvant radiation therapy was administered to 89% of pts whereas adjuvant chemotherapy and/or hormone therapy were given to 59% and 72%, respectively. The median follow-up was 91 months (7–325). Local recurrence was documented in 8 pts (3.1%). Twenty-two pts developed distant recurrence (8.7%). Bilateral breast cancer was seen in 5 cases (2%). Nine pts (3.5%) developed 2nd malignancies. RFS rate at 10 and 15 years was 84.6% and 72.6%, respectively. OS at 5, 10 and 15 years was 96%, 84% and 74%, respectively. Factors that had an effect in OS demonstrated by the multivariate regression analysis were primary tumor size, age and family history of cancer (p < 0.03). Conclusions: Clinical outcomes of stage I breast cancer in our practice is similar to that reported in international literature. This group of pts continues to have an excellent prognosis as shown by the OS rate at 5, 10 and 15 years, although high percentage of pts continue to have recurrence and die from breast cancer after 5, 10 and 15 years of follow-up. No significant financial relationships to disclose.

The Deadly Toll of Invasive Methicillin‐ResistantStaphylococcus aureusInfection in Community Hospitals

Data regarding the epidemiology, treatment, and outcomes of methicillin-resistant Staphylococcus aureus (MRSA) infections in rural and community hospitals are limited. This cohort study was conducted at 1 tertiary care hospital and 8 community hospitals in the southeastern United States. Patients with a surgical site infection (SSI) and/or bacteremia due to MRSA were prospectively identified at each study hospital during the period 1994-2003. A total of 129 patients with SSI and 564 patients with bacteremia due to MRSA were identified. Only 57 patients with SSI (44.2%) received antibiotics active against MRSA on the initial date of diagnosis; only 95 (73.6%) received an agent active against MRSA by day 7 after diagnosis of SSI due to MRSA. Ninety-five patients with SSI due to MRSA (73.6%) were readmitted to the hospital within 90 days after their original surgery. The 1-year mortality rate among patients with SSI due to MRSA was 22%. Inadequate therapy was also commonly given to patients with bacteremia: only 216 (38.3%) received antibiotics active against MRSA on the initial day of infection, and only 383 (67.9%) received an agent active against MRSA by day 7 after diagnosis. Approximately one-third of patients with bloodstream infection died during their initial hospitalization. Patients hospitalized in community hospitals were less likely to receive effective antimicrobial therapy on both the day of infection and within 7 days after infection, compared with patients in the tertiary care hospital. Inadequate therapy is commonly administered after diagnosis of SSI and bacteremia due to MRSA in patients in community hospitals.

Emerging New Clinical Patterns in the Presentation of Celiac Disease

To evaluate changes in the clinical presentation of celiac disease in southeastern Wisconsin. Retrospective medical record review. Clinical specialty practice in pediatric gastroenterology. Patients The medical records of all patients diagnosed with celiac disease at the Children's Hospital of Wisconsin between 1986 and 2003 were reviewed. Data extracted from the medical records included year of diagnosis, demographics, indications for endoscopy and biopsy, signs, symptoms, and laboratory data. Biopsy specimens were read by the pediatric pathologist and graded according to the Marsh criteria. Main Exposure Date of initial diagnosis of celiac disease. Presenting symptoms of patients with newly diagnosed celiac disease. One hundred forty-three patients were diagnosed with celiac disease. The number of patients diagnosed with celiac disease increased from 1 in 1986 to 93 in 2003. The mean age at diagnosis increased from 5.32 years for patients diagnosed before 1995 to 8.70 years for patients diagnosed after 1995. Gastrointestinal symptoms dominated in children younger than 3 years, whereas in children older than 3 years, the majority presented with non-gastrointestinal indications. The percentage of patients presenting with gastrointestinal symptoms alone decreased during the study period; 11.2% of patients diagnosed with celiac disease were overweight (body mass index > 90). Our study provides a unique longitudinal follow-up of clinical practice over a 17-year period. Currently, patients with celiac disease usually do not present with classic symptoms; they are more likely to be asymptomatic school-aged children who belong to a high-risk group.

Impact of Resection Status on Pattern of Failure and Survival After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

To better understand the impact of a microscopically positive margin (R1) on patterns of disease recurrence and survival after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. A positive resection margin after PD is considered to be a poor prognostic factor, and some have proposed that an R1 margin may be a biologic predictor of more aggressive disease. The natural history of patients treated with contemporary multimodality therapy who underwent a positive margin PD has not been described. We analyzed our experience from 1990 to 2004, which included the prospective use of a standardized system for pathologic analysis of all PD specimens. All patients who underwent PD met objective computed tomographic criteria for resection. Standard pathologic evaluation of the PD specimen included permanent section analysis of the final bile duct, pancreatic, and superior mesenteric artery (SMA) margins. First recurrences (all sites) were defined as local, regional, or distant. Survival and follow-up were calculated from the date of initial histologic diagnosis to the dates of first recurrence or death and last contact, respectively. PD was performed on 360 consecutive patients with pancreatic adenocarcinoma. Minimum follow-up was 12 months (median, 51.9 months). The resection margins were negative (R0) in 300 patients (83.3%) and positive (R1) in 60 (16.7%); no patients had macroscopically positive (R2) margins. By multivariate analysis (MVA), high mean operative blood loss and large tumor size were independent predictors of an R1 resection. Patients who underwent an R1 resection had a median overall survival of 21.5 months compared with 27.8 months in patients who underwent an R0 resection. After controlling for other variables on MVA, resection status did not independently affect survival. By MVA, only lymph node metastases, major perioperative complications, and blood loss adversely affected survival. There was no statistically significant difference in patient survival or recurrence based on R status. However, this series is unique in the incorporation of a standardized surgical technique for the SMA dissection, the prospective use of a reproducible system for pathologic evaluation of resection margins, the absence of R2 resections, and the frequent use of multimodality therapy.

Prognostic factors for patients with Ewing sarcoma (EWS) at first recurrence

10011 Background: The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%. Since 30–40% of patients with newly diagnosed, non-metastatic EWS develop recurrence, the Children's Oncology Group (COG) sought to evaluate prognostic factors for these patients. Data was derived from the phase III, multi-institutional study INT 0091. Methods: Between 1988 and 1994, five hundred and seventy-eight eligible patients with previously untreated EWS or PNET of bone were enrolled on INT 0091. Patients who experienced recurrence or disease progression as their first analytic event were considered. Survival was calculated from date of disease progression to death or last patient contact. Comparisons of the risk for death across groups were accomplished using the log-rank test. Survivor functions were estimated by the method of Kaplan and Meier. Results: Two hundred and sixty-two patients experienced disease progression or recurrence. The median time to first recurrence was 1.3 years (range 0–7.4 years) for all patients, 1.4 years (range 0 to 7.4 years) for patients with initially localized disease and 1 year (range 0 to 6 years) for patients with initially metastatic disease. Time to first recurrence from date of initial diagnosis was a predictor of post-recurrence survival (p&lt;0.0001). Twenty-one percent of patients whose disease recurred or progressed experienced first recurrence 2 or more years from initial diagnosis and had an estimated 5 year post-recurrence survival of 30%. This compares with 7% for those whose first recurrence or progression was earlier. No statistical difference was detected when patients whose disease recurred &lt; 12 months were compared with those whose recurrence was 12–24 months from initial diagnosis. Significant risk factors for death after recurrence included metastatic disease at initial diagnosis, elevated LDH at initial diagnosis and female gender. In patients non-metastatic at initial diagnosis pelvic primary site was also a risk factor for death after recurrence. Conclusions: Patients with longer time to first recurrence represent the subset of patients most likely to survive following recurrence. All patients with recurrent Ewing sarcoma would benefit from collaborative trials to investigate new therapeutic options. No significant financial relationships to disclose.

Variation in prognostic factors in hormone receptor-positive breast cancer patients who responded to hormonal therapy and those who did not: A retrospective analysis

11514 Background: Hormone receptor positive patents historically had a better prognosis than their receptor negative counterparts when other parameters are balanced. However not all the patients expressing Estrogen and progesterone respond well to the hormonal manipulation. Therefore we thought of doing a retrospective analysis of our hospital data to find out the differences in the prognostic factors in therapy responders and non responders. Methods: The study was conducted at tertiary care cancer center from India. Between 2002–2003 a total of 120 breast cancer patients who expressed either Estrogen receptor (ER) or progesterone receptor (PR) were analyzed. Only patients with metastatic breast cancer were analyzed. The patients were treated with our standard institutional protocol at the beginning according to the stage of the disease. The details and baseline characters were shown in table . Results: The responders tend to be post menopausal, having low grade, node negative tumors, expressed both ER and PR, and had long interval from the date of initial diagnosis. However tumor size and the site of metastasis (visceral vs. non visceral) did not alter the outcome to hormone therapy. Conclusion: patients who are having higher age, lower tumor grade, lower number of nodes, longer disease free interval after adjuvant therapy and expressing both receptors tend to respond to hormone therapy better than those who had the opposite characters. However as thought earlier, presence of visceral metastasis or larger tumors at the time of initial diagnosis dose not preclude response to hormonal manipulation. [Table: see text] No significant financial relationships to disclose.

POPULATION-BASED EPIDEMIOLOGY AND CLINICAL CHARACTERISTICS OF PEDIATRIC IBD IN AN INTEGRATED HEALTH PLAN IN NORTHERN CALIFORNIA

Purpose: To define the epidemiology and clinical characteristics of children with IBD in a population-based registry. Methods: Kaiser Permanente is an integrated health plan in northern California serving a population of 3.2 million persons. Analysis of the Kaiser Permanente IBD Registry revealed 569 patients, 0-18 years of age, with IBD during 1996-2002. Confirmation of the diagnosis, the date of initial diagnosis, the extent of disease, drug and surgical treatment were obtained through review of the medical record and linkage to other computerized data. Results: During the study period the annual incidence per 100,000 was 6.1 for IBD, Crohn's disease (CD) 3.2, ulcerative colitis (UC) 2.9 and indeterminate colitis (IC) 0.2. The peak incidence of CD was equal at ages 10-14 vs. 15-19 while UC incidence peaked at ages 15-19. A minor gender preference was noted for CD and UC in females. Over 60% of patients were Caucasian while African Americans had more CD and Hispanics and Asian had more UC. Location of CD: isolated small bowel 11%, colon 25%, ileocolonic 41% and 15% had upper GI involvement in addition to other locations. Location of UC: Lt colon 41% (distal disease/proctitis 24%) and pancolitis 48%. Oral prednisone and 6MP/azathioprine use was 73% and 47% respectively for CD compared to 69% and 24% for UC. Oral and rectal mesalamine use for UC was 63% and 22% respectively. A colectomy was performed in 7% of patients with UC. Conclusions: These findings contribute additional data on the incidence of IBD in the US. Differences in age of presentation and ethnicity were found for CD compared to UC. The use of oral prednisone was similar for CD and UC and immune modulators were more readily used in CD. Rectal mesalamine was used in the majority of children with distal UC. Compared to published data in adults, a large proportion of children have ulcerative pancolitis, however, only a minority require a colectomy.

Is routine chest radiography a useful test in the follow up of all adult patients with soft tissue sarcoma?

Following treatment for localized soft tissue sarcoma the risk of relapse is either locally or in the lungs. In Edinburgh patients are reviewed every 6 months with a chest X-ray (CXR). The radiation exposure over a 10 year follow up remains small, but it is unclear if all patients, irrespective of the initial grade of their primary tumour, require this. To determine the pick up rate of lung metastases by routine CXR over a 10 year period and to review the primary histology. Adult patients on routine follow up between 1994 and 2004 were identified and the notes of those with lung metastases reviewed. Data was collected on their initial histology, and date and method of diagnosis of lung metastases. 179 patients were under follow up. 24 (13%) developed lung metastases. For 2, notes were not found. 6 (27%) had metastases diagnosed by routine CXR, 9 (41%) had metastases diagnosed by non routine CXR and 7 (32%) had metastases diagnosed by CT. On review of histology none were grade 1, 4 (18%) were grade 2 and 18 (82%) were grade 3. 155 patients received. 6 monthly CXR for 10 years with no detection of lung metastases. Lung metastases occurred in a minority of patients (13%) and most (82%) occurred in patients with grade 3 tumours. No patients with grade 1 tumours developed lung metastases. Thus routine CXR may be appropriate on grade 3 tumours, but not on lower grade tumours where other risk factors are absent.

Retroperitoneal nodal metastasis in primary and recurrent granulosa cell tumors of the ovary

Objective. To describe the incidence of retroperitoneal pelvic or paraaortic lymph node metastasis in patients with primary and recurrent ovarian granulosa cell tumors. Methods. At Memorial Sloan-Kettering Cancer Center, we conducted a retrospective chart review of all patients with ovarian granulosa cell tumors managed as inpatients from January 1991 to July 2005. The initial date of diagnosis ranged from 1971 to 2005. Results. We identified 68 patients with a median age of 49 years (mean, 47.5 years; range, 19–78 years). Sixty-four (94%) patients had adult type and 4 (6%) had juvenile granulosa cell tumors. Fifty-three (78%) patients had their initial surgery at another institution and 55 (81%) were incompletely surgically staged at diagnosis due to the absence of pelvic and/or aortic lymph node dissection. Patients were assigned an International Federation of Gynecology and Obstetrics (FIGO) stage that included IA, 39; IC, 15; IIB, 3; IIC, 3; IIIC, 1. In 7 patients, the original stage was not assigned. Only 16 (24%) patients had a pelvic lymph node sampling and 13 (19%) also had a paraaortic lymph node sampling at primary surgery or at restaging surgery performed shortly following initial diagnosis; however, in these cases, lymph nodes were negative for metastasis. The median number of pelvic lymph nodes removed was 10 (mean, 11.6 nodes; range, 0–36 nodes). The median number of paraaortic lymph nodes removed was 4 (mean, 6 nodes; range, 0–19 nodes). Nine of 15 (60%) of patients managed initially at our institution were surgically staged compared to 4 of 53 (7.5%) who were managed initially elsewhere ( P < 0.001). Thirty-four patients with recurrent granulosa cell tumors were managed during the study, 31 (91%) had adult type granulosa cell tumor, and 3 had juvenile histology. Thirty-three of 34 patients who recurred were incompletely surgically staged at the initial operation. Original “clinical” FIGO stage for patients who recurred included IA, 15; IC, 8; IIB, 1; IIC, 3; IIIC, 1; and in 6 patients, the original stage was not available. The median disease-free interval to first recurrence was 63 months (mean,69.4 months; range, 4–170 months). First recurrence sites included pelvis, 24/34 (70%); pelvis and abdomen, 3 (9%); retroperitoneum only, 2 (6%); pelvis and retroperitoneum, 2 (6%); pelvis/abdomen/retroperitoneum, 1(3%); abdomen only, 1 (3%); and bone, 1 (3%). Conclusions. Complete surgical staging was performed in approximately 1/5 women with ovarian granulosa cell tumors; however, in those initially surgically staged, no nodal metastasis was identified. Clinical stage IA disease was the most common original diagnosis in women who recurred, and approximately 15% of first recurrences appear to involve the retroperitoneum.

Combined Overexpression of Bcl-2 and SOCS3 Is Associated with Decreased Survival in a Cohort of Patients with De Novo Follicular Lymphoma.

Follicular lymphomas (FL) comprise approximately twenty-five percent of all cases of non-Hodgkin's lymphomas (NHL) in humans and are marked by a highly variable clinical course, ranging from indolent to rapidly progressive disease. The genetic hallmark of FL is t(14;18), resulting in deregulated expression of Bcl-2 and abrogation of the majority of apoptotic pathways in B and T lymphocytes. Data suggest that while t(14;18) is sufficient to initiate an oncogenic pathway, Bcl-2 alone is a relatively weak oncogene and requires additional cooperating genetic lesions for neoplastic transformation to occur. We previously demonstrated that Bcl-2 overexpression is associated with overexpression of the suppressor of cytokine signaling-3 (SOCS3) gene in a group of patients with de novo FL. In the current study, to determine whether SOCS3 overexpression has prognostic significance in FL, we performed a retrospective cohort study utilizing de novo FL lymph node tissue banked at Yale University. Eligibility criteria included subjects with FL tissue diagnosed as either histologic Grades I or II and harboring t(14;18)+. Subjects with transformed FL at presentation, HIV, other malignancy, or chronic autoimmune disorders were excluded. Subjects were segregated into two cohorts based on standard immunohistochemistry using SOCS3 and Bcl-2 antisera on FL tissue: Cohort 1 harboring combined overexpression of Bcl-2 and SOCS3 within the follicular center cell region and Cohort 2 harboring sole overexpression of Bcl-2. Immunostaining of germinal center B cells from benign hyperplastic tonsil tissue was used as a negative control for SOCS3 and Bcl-2 expression. Medical record review was performed to determine survival time from the date of initial diagnosis and to calculate the Follicular Lymphoma International Prognostic Index (FLIPI). Eighty-two subjects met eligibility criteria and had medical records available for review. Of these, 42 overexpressed both Bcl-2 and SOCS3 and 40 expressed Bcl-2 alone. Median survival in Cohort 1 was 8 years (95% CI 3.68, 12.32) compared to a median survival of 16.5 years (95% CI 14.56, 20.44) for Cohort 2 (Kaplan Meier survival analysis; p=0.01 log rank test). FLIPI score was not significantly different between the two cohorts. The decrease in survival in Cohort 1 (harboring combined overexpression of Bcl-2 and SOC3) remained statistically significant after adjustment for the FLIPI score (Cox Regression Analysis, p=0.01). Transformation to high grade NHL occurred in 8 of 42 (19%) and 2 of 40 (5%) subjects in Cohort 1 and Cohort 2, respectively (p =0.05, Chi Square Test). This large retrospective cohort study demonstrates that FL harboring combined overexpression of Bcl-2 and SOCS3 was associated with an approximately 50% reduction in survival from the time of diagnosis as compared to subjects with FL marked by overexpression of Bcl-2 alone. This effect was independent of the FLIPI score. These findings suggest that overexpression of SOCS3 protein may be a poor prognostic factor in patients with de novo FL. Further studies will examine whether combined overexpression of Bcl-2 and SOCS3 results in deregulation of cellular pathways which portend a more aggressive natural history of follicular lymphoma.

Variates of Survival in Metastatic Uveal Melanoma

The course and outcome of metastatic uveal melanoma are not well described. We evaluated the survival of our patients with metastatic uveal melanoma, described factors that correlated with survival, and evaluated the influence of screening tests on time of detection and survival. All patients with metastatic uveal melanoma seen at Memorial Sloan-Kettering Cancer Center between 1994 and 2004 were identified from our database. We recorded date of initial diagnosis, date of metastatic disease, date of last follow-up, site of the first metastasis, how the first metastasis was discovered, treatment, and outcome of therapy. The estimated median survival of the 119 patients analyzed was 12.5 months; 22% of patients were alive at 4 years. Five variates correlated independently with prolonged survival: Lung/soft tissue as only site of first metastasis, treatment with surgery or intrahepatic therapy, female sex, age younger than 60, and a longer interval from initial diagnosis to metastatic disease. Discovering metastatic disease in asymptomatic patients did not correlate with overall survival; 89% of patients had a single organ as the site of first metastasis. Although liver was the most common site, 39.5% of patients had nonliver sites, most commonly lung, as the first site of metastasis. A substantial subset of patients with metastatic uveal melanoma survive more than 4 years with metastatic disease. Data on variates of survival and site of first metastasis may guide strategies for screening patients, although our data failed to show a survival advantage in discovering asymptomatic metastatic disease.

Platform Session B: Clinical Neurophysiology/Clinical Epilepsy 3:00 p.m.–6:00 p.m.

Platform Session B: Clinical Neurophysiology/Clinical Epilepsy 3:00 p.m.–6:00 p.m.

Epidemiology, clinical characteristics, outcome, morbidity and mortality in acromegaly based on the Spanish Acromegaly Registry (Registro Espanol de Acromegalia, REA).

To undertake a multicentre epidemiological study reflecting acromegaly in Spain. Voluntary reporting of data on patients with acromegaly to an online database, by the managing physician. Data on demographics, diagnosis, estimated date of initial symptoms and diagnosis, pituitary imaging, visual fields, GH and IGF-I concentrations (requested locally), medical, radiotherapy and neurosurgical treatments, morbidity and mortality were collected. Data were included for 1219 patients (60.8% women) with a mean age at diagnosis of 45 years (s.d. 14 years). Reporting was maximal in 1997 (2.1 cases per million inhabitants (c.p.m.) per year); prevalence was globally 36 c.p.m., but varied between 15.7 and 75.8 c.p.m. in different regions. Of 1196 pituitary tumours, most were macroadenomas (73%); 81% of these patients underwent surgery, 45% received radiotherapy and 65% were given medical treatment (somatostatin analogues in 68.3% and dopamine agonists in 31.4%). Cures (GH values (basal or after an oral glucose tolerance test) <2 ng/ml, normal IGF-I, or both) were observed in 40.3% after surgery and 28.2% after radiotherapy. Hypertension (39.1%), diabetes mellitus (37.6%), hypopituitarism (25.7%), goitre (22.4%), carpal tunnel syndrome (18.7%) and sleep apnoea (13.2%) were reported as most frequent morbidities; 6.8% of the patients had cancer (breast in 3.1% of the women and colon in 1.2% of the cohort). Fifty-six patients died at a mean age of 60 years (s.d. 14 years), most commonly of a cardiovascular cause (39.4%); mortality was greater in patients given radiotherapy (hazard ratio 2.29; 95% confidence interval 1.03 to 5.08; P=0.026), and in those in whom GH and IGF-I concentrations were never normal (P<0.001). This acromegaly registry offers a realistic overview of the epidemiological characteristics, treatment outcome and morbidity of acromegaly in Spain. As active disease and treatment with radiotherapy are associated with an increase in mortality, efforts to control the disease early are desirable.

Economic consequences of venous thromboembolism following major orthopedic surgery.

Venous thromboembolism (VTE) is a frequent and potentially costly complication of major orthopedic surgery. To estimate the economic consequences of VTE following major orthopedic surgery. Using a large healthcare claims database, we identified all patients who underwent total hip replacement, major knee surgery, or hip fracture repair from January 1993 to December 1998. Patients with clinical VTE (cases) were identified based on a diagnosis of deep vein thrombosis or pulmonary embolism within 90 days of surgery (index admission) and > or =1 prescription for warfarin or unfractionated heparin within 30 days of the date of initial VTE diagnosis. Each case was matched (using age and procedure type) to 2 randomly selected patients who did not have any claims for clinical VTE (matched controls). Utilization and billed charges were then examined over a 90-day period following admission. Cases were stratified based on whether VTE was first noted during the index admission or thereafter. A total of 11 960 patients were identified who underwent total hip replacement, major knee surgery, or hip fracture repair (n = 3171, 3955, 4834, respectively). Over a 90-day period, 259 patients (2.2%) developed clinical VTE. Most cases (61.8%) occurred after hospital discharge. For patients with in-hospital VTE, mean length of stay for the index admission was 4.5 days longer than that of matched controls (11.1 vs 6.6); by day 90, there was a 5.4-day difference in total hospital days. Mean billed charges for the index admission were 17,552 higher US dollars (52,037 US dollars vs 34,485 US dollars); the difference rose to 18,834 US dollars by day 90 (54,480 US dollars vs 35,646 US dollars). For patients who developed clinical VTE following hospital discharge, there was a 3.4-day difference in total hospital days at day 90 (10.2 vs 6.8) as a result of readmissions for VTE; mean total billed charges at day 90 were 5765 US dollars higher (41,411 US dollars vs 35,646 US dollars). Among patients who have undergone major orthopedic surgery, the economic consequences of VTE are substantial, regardless of the setting in which it occurs.

Oligodendroglioma: does deferring treatment compromise outcome?

This study reports the University of Florida experience treating oligodendrogliomas with the goal of identifying the factors that predict favorable outcome. Between 1958 and June 1998, 51 patients (aged 5-75 years) were diagnosed with pure oligodendroglioma at the University of Florida. Histologic grade was anaplastic in 19 patients, low-grade in 30 patients, and unknown in one patient. Twelve patients were treated with surgery alone (10 with low-grade tumors). Thirty-nine patients underwent postoperative radiotherapy after surgery (plus chemotherapy in four patients). A biopsy was performed in 10 patients, 40 underwent subtotal or gross total resection, and one had surgery of unknown extent. Thirteen patients with a radiographic abnormality consistent with a low-grade glioma had the initiation of definitive treatment (i.e., surgery with or without radiotherapy) deferred for a median of 4.5 years before undergoing treatment for worsening symptoms or radiographic progression. Absolute survival for the entire group (51 patients) at 5, 10, and 20 years from the date of initial treatment was 61%, 37%, and 31%, respectively, and at 5, 10, and 20 years from the date of initial diagnosis was 65%, 43%, and 34%, respectively. No patient died of intercurrent disease. Multivariate analysis for absolute survival from the time of initial treatment demonstrated young age (young patients fared better than older patients) and size (<5 cm better than > or =5 cm) to be significant variables. No patient under the age of 21 years (n = 8) at the time of diagnosis has died in this series. Deferring aggressive treatment did not alter survival. Multivariate analysis for favorable absolute survival based on the time from initial diagnosis demonstrated young age and presentation with seizures alone to be statistically significant for favorable outcomes. Approximately one third of patients with oligodendroglioma appear to be cured with aggressive treatment. Age is the most important predictor of long-term progression-free and absolute survival with young patients (especially aged <21 years) doing much better than older patients. Deferring aggressive treatment (surgery and/or radiation) until symptoms clearly indicate tumor progression does not compromise outcome for a select group of patients who are diagnosed at a young age with a nonenhancing mass on MR and seizures as the lone presenting symptom.

Surgical resection of pulmonary and extrapulmonary recurrences of uterine leiomyosarcoma.

The objective was to determine long-term survival and predictors of outcome in a retrospective cohort of patients who underwent surgical resection of recurrent uterine leiomyosarcoma (LMS). Between January 1991 and March 2001, 41 patients who underwent surgical resection for recurrent uterine leiomyosarcoma were identified. The records of these patients were reviewed and abstracted data included patient age, date of initial diagnosis, tumor histology and grade, residual tumor after all operations, the use of adjuvant therapy, dates and sites of all recurrences, and disease status at last follow-up. Survival was determined from the time of first recurrence to last follow-up. Survival curves were estimated using the Kaplan-Meier method and P values were generated using the likelihood ratio test from the Cox proportional hazards model and chi(2) analysis. Forty-one patients with recurrent uterine LMS (17 local pelvic, 18 distant, 6 both) underwent surgical resection at time of first recurrence. A thoracic procedure alone was performed in 13 cases. Information on residual disease was available for 37 patients. The disease-specific 2-year survival for all 41 patients was 71.2% (95% CI: 58.1, 87.3). In univariate analysis, time to first recurrence and optimal resection were significantly associated with longer overall survival. Optimal surgical resection for recurrent uterine leiomyosarcoma may provide an opportunity for long-term survival in a select patient population. Time to first recurrence and optimal surgical resection were predictors of improved outcome in this study.

Breast-conservation therapy in early-stage breast cancer patients with a positive family history.

Our goal was to evaluate the role of breast-conservation therapy in early-stage breast cancer patients with a family history (FH) of breast cancer. Between 1970 and 1994, 1324 female patients with breast cancer were treated with breast-conservation therapy at our institution. From these, we identified 985 patients with stage 0-II breast cancer and who had available information on FH status. FH was considered positive in any patient who had a relative who had been previously diagnosed with breast cancer. Disease-specific survival was calculated from the date of initial diagnosis using the Kaplan-Meier method. The stage distribution for the 985 patients was as follows: 0 in 65 (7%), I in 500 (51%), and II in 420 (43%). The median age was 50 years (range, 21-88), with a median follow-up time of 8.8 years (range,.25-29). The median tumor size was 1.5 cm. FH was positive in 31%. There were no significant differences in locoregional recurrence, distant recurrence, disease-specific survival, or incidence of contralateral breast cancer in patients with a positive FH versus patients with a negative FH. Breast-conservation therapy is not contraindicated in early-stage breast cancer patients with a positive FH.

Occult primary breast carcinoma presenting as axillary lymphadenopathy

Background: The objective of this study was to review the need for radiotherapy or not in patients with occult primary breast cancer presenting with axillary metastases treated with breast conservation usually with no surgery to the breast. Methods: From 1975 to 2001, 58 patients were treated with axillary lymphadenopathy from a cryptic primary breast carcinoma. After clinical and radiological assessment, 29 patients retained a diagnosis of occult primary breast carcinoma. Clinical and pathological data were collected retrospectively on the 29 patients and survival was calculated from the date of initial diagnosis using the Kaplan–Meier method. The median follow-up was 44 months. Results:Median age at diagnosis was 57 years (range 28–81 years). Sixteen patients had radiotherapy to the ipsilateral breast. Eleven patients received no local therapy to the ipsilateral breast and two patients had quadrantectomies which were negative for malignancy. Locoregional relapse occurred in 12.5% of patients who had received radiotherapy and 69% of those who had not received any radiotherapy ( P=0.02). Fifty-seven per cent of patients having a local relapse were salvaged with further surgery. The eventual breast conservation rate was 93%. Patients who received radiotherapy to the breast had significantly improved relapse-free survival (HR=0.31; P = 0.04) and local relapse-free survival (HR=0.09; P=0.004). There were no significant differences in overall survival between those patients who had breast irradiation and those who did not (HR 0.91; 95% CI 0.18–4.5). Conclusion: Occult primary carcinoma with axillary metastases can be treated successfully with breast preservation but radiotherapy to the breast is necessary to minimize the risk of locoregional recurrence.

Lifetime cancer-attributable cost of care for long term survivors of colorectal cancer

OBJECTIVES: We aimed to determine cancer-related medical care costs for long term survivors of colorectal cancer. METHODS: The SEER-Medicare database was used to measure lifetime cancer-attributable costs of care for those with colorectal cancer surviving at least 5 yr versus age- and gender-matched controls. Costs were directly estimated, stratified by age at diagnosis and stage at diagnosis, for years 6–11 after diagnosis and then modeled to estimate lifetime costs. Cost differences between cancer cases and controls were compared to expected costs based on published guidelines for postcancer surveillance. RESULTS: Lifetime medical costs for long term survivors (future years not discounted) were up to $19,516 higher than control costs, and were highest for younger age groups and those with early-stage disease. Excess costs for cancer survivors exceeded expected surveillance costs by $2,223–8,822 for years 6–10 from the date of initial diagnosis. CONCLUSIONS: Cancer-attributable medical costs can be substantial for long term survivors, and exceed expected costs of surveillance. Future research is need to determine the components of excess cost in this survivor group.