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PubMed1997

Therapeutic management of hematological malignancies in elderly patients. Biological and clinical considerations. Part II: Non-Hodgkin lymphomas and Hodgkin's disease.

Increased knowledge of the nature and biology of lymphoid cells has provided more rational classification schemes, and has improved therapeutic strategies. However, non-Hodgkin lymphomas (NHL) as well as Hodgkin's disease (HD) show a less favorable outcome in elderly compared to young patients. The poorer outcome in elderly patients with NHL is largely due to chemotherapy-related issues, although other age-related factors may contribute to determine a poor prognosis, such as the presence of more aggressive pathological subtypes and an increase in extranodal vs nodal presentations. Similarly, HD patients older than 50 years have higher rates of advanced disease, B symptoms, and histological types associated with poor prognosis at presentation. The poor prognosis in lymphoid malignancies also appears to be attributable to inadequate treatment. However, the inability to administer full therapy may be real, due to the high percentages of deaths caused by severe infections and intercurrent disease (cardiac, renal, lung) related to diminished organ function. The availability of growth factors may help to reduce the incidence of severe neutropenia and other related septic conditions.

Aged↗

PubMed2000

Predictive factors of death in primary lung cancer patients on admission to the intensive care unit.

OBJECTIVE: To assess the lung cancer patient's prognosis in the intensive care unit with early predictive factors of death. DESIGN: Retrospective study from July 1986 to February 1996. SETTING: Medical intensive care unit at a university hospital. PATIENTS: Fifty-seven patients with primary lung cancer admitted to our medical intensive care unit (MICU). MEASUREMENTS AND RESULTS: Data collection included demographic data (age, sex, underlying diseases, MICU admitting diagnosis) and evaluation of tumor (pathologic subtypes, metastases, lung cancer staging, treatment options). Three indexes were calculated for each patient: Karnofsky performance status, Simplified Acute Physiology Score (SAPS) II, and multisystem organ failure score (ODIN score). Mortality was high in the MICU: 66% of patients died during their MICU stay, and hospital mortality reached 75%. In multivariate analysis, acute pulmonary disease and Karnofsky performance status < 70 were associated with a poor MICU and post-MICU prognosis. For the survivors, long-term survival after MICU discharge depended exclusively on the severity of the lung cancer. CONCLUSIONS: We confirmed the high mortality rate of lung cancer patients admitted to the MICU. Two predictive factors of death in MICU were identified: performance status < 70 and acute pulmonary disease.

APACHE↗

PubMed2004

Elevated serum epidermal growth factor receptor level in stage IV thymoma.

Using the enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as a predictor of the development and extension of thymoma. Serum samples were collected from 31 patients with thymoma and 16 patients with nonmalignant thoracic disease before clinical treatment. There was no difference between the serum EGFR levels of the patients with thymoma and the nonmalignant controls, being 49.1 +/- 136.3 and 22.6 +/- 7.3 fm/ml, respectively ( P = 0.11). However, patients with stage IV thymoma had significantly higher EGFR levels than those with stage I or stage II thymoma, the respective values being 127.8 +/- 243.9, 10.9 +/- 9.2 ( P = 0.02), and 19.7 +/- 10.6 ( P = 0.0433) fm/ml. The serum EGFR levels were similar in the pathological subtypes. These findings suggest that serum EGFR levels may serve as a marker that could be used as a diagnostic indicator of the invasion of thymoma.

Biomarkers, Tumor↗

PubMed2001

Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

Adult↗

PubMed2001

Expression of the prothymosin-a gene as a prognostic factor in lung cancer.

Prothymosin-alpha (PTalpha) is known to play a role in cell proliferation, and the PTalpha mRNA level may reflect the degree of proliferation of tumor cells. It has been reported that PTalpha mRNA levels are higher in human colon and liver cancer tissues than in the adjacent normal tissues. We examined the mRNA levels of PTalpha and c-myc in 20 lung cancers, using Bas 2500Mac systems. The PTalpha and c-myc mRNA levels in lung cancer tissues were higher than those in normal lung tissues; however, the PTalpha mRNA levels did not correlate with the stage or pathological subtype of the lung cancer and there was no correlation between the expression of PTalpha and c-myc. PTalpha mRNA overexpression in lung cancer was correlated with a poor prognosis.

Aged↗

PubMed2006

Intracranial non-Hodgkin's MALT lymphoma mimicking a large convexity meningioma.

Primary presentation of an intradural Non-Hodgkin's lymphoma is rare. Recently these B cell lymphomas of mucosa associated lymphoid tissue (MALT) have gained acceptance as an important pathological subtype and are distinguishable from other primary CNS lymphomas that exhibit aggressive behaviour. Over the past decade a number of these lesions have been reported to resemble a meningioma both intra-operatively and radiologically. The authors outline such a case of marginal zone B cell lymphoma that clinically and radiologically resembled a meningioma. This case illustrates the rare occurrence of low grade dural B cell lymphoma and the need to consider this entity in the differential diagnosis of CNS lesions, if appropriate targeted therapy is to be administered.

Aged↗

PubMed2003

Elevated serum epidermal growth factor receptor level is correlated with lymph node metastasis in lung cancer.

BACKGROUND: Using an enzyme immunoassay for epidermal growth factor receptor (EGFR), we investigated whether serum EGFR levels could be used as predictors of the development and extent of lung cancer. METHODS: The study included 106 lung cancer patients and 16 patients with nonmalignant thoracic disease. Serum samples were collected before clinical treatment. RESULTS: There was no difference between serum EGFR levels in patients with lung cancer (21.275 +/- 22.035 fm/ml) in comparison with those in nonmalignant-disease controls (22.630 +/- 7.330 fm/ml; P = 0.8083). However, lung cancer patients with lymph node metastasis (23.515 +/- 20.065 fm/ml) had significantly higher EGFR levels compared with those in patients without lymph node metastasis (16.390 +/- 10.970 fm/ml; P = 0.0228). The serum EGFR levels were similar in samples from lung cancer patients with various pathological subtypes. There was no difference in the prognosis between the lung cancer group with normal EGFR levels (<850 ng/ml) and the group with elevated EGFR levels (>850 ng/ml). CONCLUSION: Serum EGFR levels may serve as a marker that can be used as an indicator of lymph node metastasis in lung cancer. However, there was no difference between levels in patients with lung cancer and those in nonmalignant-disease controls, indicating that the measurement of serum EGFR levels was of limited value in the detection of lung cancer.

Aged↗

PubMed2006

Toxicity and efficacy of protracted low dose temozolomide for the treatment of low grade gliomas.

Protracted low dose temozolomide (75 mg/m(2)/day on days 1-21 of 28 days) offers potential advantages over standard temozolomide schedules (200 mg/m(2)/day on days 1-5 of 28 days) including greater cumulative drug exposure and depletion of O(6)-alkylguanine DNA alkyltransferase levels, theoretically overcoming intrinsic chemoresistance. We retrospectively review our experience in 25 patients with pathologically proven low grade gliomas (LGG) treated with protracted low dose temozolomide to primarily quantify its toxicity and secondarily to assess efficacy. None had previously received radiation. Tumor response was graded based on changes in tumor size, steroid requirements, and clinical exam. About 243 cycles of protracted low dose temozolomide were administered. Three patients (12%) were changed to standard temozolomide dosing due to side effects, including intractable nausea (n = 2) and multiple cytopenias (n = 1). The most frequent toxicities were fatigue (76%), lymphopenia (72% [48% high grade]), constipation (56%), and nausea (52%). High grade toxicities (other than lymphopenia) included secondary malignancy, pruritus, hyponatremia, neutropenia, leukopenia, and cognitive decline (n = 1 for each). Tumor response rate was 52% and and disease control rate was 84%. Six month PFS was 92% and 12 month PFS was 72%. Response rates and PFS were independent of pathological subtype, deletion status, and indication for chemotherapy. Protracted low dose temozolomide has a distinct spectrum of toxicities compared to standard dosing but is well tolerated in most patients and may provide improved response rates compared to standard dosing. The results of larger randomized trials are needed to assess its potential advantages over other management schemes.

Adult↗

PubMed2002

Elevated serum pro-mMP2 levels in patients with advanced lung cancer are not suitable as a prognostic marker.

Using the one-step sandwich enzyme immunoassay for pro-MMP2, we investigated whether the serum pro-MMP2 levels could be used as predictors of the development and extension of lung cancer. The study included 52 lung cancer patients and 26 nonmalignant thoracic disease patients. Serum samples were collected before clinical treatment. The serum pro-MMP2 levels were found to be elevated in patients with lung cancer (1006.3+/-37.4 ng/ml) in comparison with nonmalignant controls (767.7+/-41.6 ng/ml) (P = 0.0002). In addition, stage IIIb lung cancer patients (1167.2+/-124.2 ng/ml) had significantly higher pro-MMP2 levels compared with stage I patients (936.0+/-44.8 ng/ml, P = 0.0431). The serum pro-MMP2 levels were similar in the samples between the pathological subtypes. As a result, the serum pro-MMP2 levels may serve as a marker that can be used as a diagnostic indicator of higher stages in lung cancer. There was no difference in the prognosis between the group with normal pro-MMP2 levels (<850 ng/ml) and the group of elevated pro-MMP2 levels (>850 ng/ml), thus indicating that serum analyses of the pro-MMP2 levels were of limited value in the prognosis of lung cancer.

Biomarkers, Tumor↗

PubMed1986

Lymphocyte-depleted Hodgkin's disease. Clinicopathologic review of 25 patients.

Clinicopathologic material from 25 patients with lymphocyte-depleted Hodgkin's disease was reviewed. The median age of the patients was 57 years. The patients had no prior diagnosis of Hodgkin's disease and were divided according to pathologic subtype of lymphocyte-depleted Hodgkin's disease: 11 diffuse fibrosis, 10 reticular, and four not otherwise specified. The clinical presentation included B symptoms of fever, weight loss, or night sweats (92 percent), subdiaphragmatic disease (88 percent), frequent marrow involvement (56 percent), and advanced-stage disease (100 percent). Four of 11 patients with diffuse fibrosis had peripheral adenopathy as compared with seven of 10 patients with the reticular subtype (p = 0.3); 10 of 11 patients with diffuse fibrosis had marrow involvement compared with two of nine patients with the reticular subtype (p = 0.006). Among patients who received chemotherapy, median survival was longer in the diffuse fibrosis subtype (nine patients, 39 months) than in the reticular subtype (10 patients, 10 months), p = 0.005. Of the 17 patients who received more than one cycle of combination chemotherapy with mechlorethiamine, vincristine, procarbazine, and prednisone, the median survival was 36 months with 11 (65 percent) complete remissions. In eight patients, disease remains in remission (12 to 127 months) with five patients surviving beyond five years. These results indicate that lymphocyte-depleted Hodgkin's disease has at least two clinicopathologic subtypes and is curable if adequate therapy can be given.

Adult↗

PubMed1983

Anaplastic seminoma.

Fourteen patients with anaplastic seminoma were analyzed retrospectively. At the time of presentation anaplastic seminoma has similar prognosis stage for stage as the classic seminoma. However, the distinctive histologic findings and the high rates of local invasion and of elevations of serum beta-subunit human chorionic gonadotropin serve to distinguish anaplastic seminoma from the classic seminoma. These features, suggesting a possibly greater metastatic potential for anaplastic seminoma, warrant its continued identification as a distinct pathologic subtype.

Adult↗

PubMed1992

Glassy cell carcinoma of the cervix: a bimodal treatment strategy.

Glassy cell carcinoma of the cervix is a distinct clinicopathologic entity. This infrequent pathologic subtype is an aggressive biologic tumor associated with a rapid clinical course and poor outcome with conventional treatment modalities in the majority of cases. In a 12-year period from July 1976 to June 1988, 32 cases of glassy cell carcinoma of the cervix were identified. This accounted for 5.3% of all cervical carcinomas. The mean age was 10 years younger than that of other histologic subtypes. A disproportional number of patients with glassy cell carcinoma had malignancies of early clinical stages. The 5-year survival of patients with Stage IB glassy cell carcinoma of the cervix was 45% when treated with primary radical surgery in contrast to 90% for squamous cell and 78% for adenocarcinoma. When bimodal therapy with radical surgery and radical radiotherapy was used, the survival of patients with Stage IB glassy cell carcinoma improved to 87%. Survival of patients with Stage II glassy cell carcinoma of the cervix improved from 50% to 85% with combined radical surgery and radiotherapy. Despite a combination of radical surgery and radiotherapy, complications were minimal.

Adenocarcinoma↗

PubMed1991

Mechlorethamine, vinblastine, procarbazine and prednisolone (MVPP) for advanced Hodgkin's disease.

Between January 1972 and October 1985, 60 patients with advanced Hodgkin's disease were treated with mechlorethamine/vinblastine/procarbazine/prednisolone (MVPP). The complete remission (CR) rate was 50%; the introduction of computed tomography in 1980 reduced the proportion of CR from 62% to 30% (P = 0.017) as a consequence of residual mediastinal abnormality of uncertain significance. With a median follow-up of 9 years, actuarial 5 and 10-year overall survival was 70% and 57%, respectively, with 79% and 65% free from Hodgkin's disease. Only age and pathological subtype influenced survival sufficiently to be of prognostic significance, though the effect of serum albumin, ECOG performance status and B symptoms on Hodgkin's disease mortality may have been clinically important.

Adolescent↗

PubMed1986

Local control and survival of breast cancer treated by limited surgery followed by irradiation.

Between 1960 and 1978, 324 patients with early breast cancer were treated by lumpectomy with or without axillary dissection followed by radiation therapy. All were followed for a minimum of 5 years. All patients were, retrospectively, classified T1, T2, N0, N1a, in the TNM (U.I.C.C.) Classification. The retrospective analysis of the local-regional patterns of failure revealed that young age (less than or equal to 32 years) and premenopausal status were associated with an increased rate of local failure, whereas tumor size and location showed no influence. No pathological features were associated with an increased risk of local recurrence, whether pathological subtypes, Scarff Bloom and Richardson grading, intraductal associated component, or vascular involvement. The absolute 5 year disease-free survival rate was 87% in patients who recurred and 93% in those who did not. The absolute 10 year disease-free survival rates were 75 and 82%, respectively. Therefore, these results confirm that loco-regional failure does not significantly influence the disease-free survival.

Adult↗

PubMed1995

Microscopic extracapsular extension in the axilla: is this an indication for axillary radiotherapy?

PURPOSE: Although the axilla is often treated with radiotherapy (RT) postoperatively when microscopic extracapsular extension (ECE) of lymph nodal metastases is present, little data are available to assess axillary failure in the absence of such treatment. As it has been the practice at this institution to withhold axillary irradiation in the presence of microscopic extracapsular spread, we retrospectively analyzed our results for axillary recurrence, disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: Clinical records were reviewed of 82 women with Stage II node positive breast cancer treated with lumpectomy, axillary dissection, and RT in addition to systemic chemo/hormonal therapy. Axillary surgery consisted of a level I, II, +/- III dissection, with a median of 16.5 nodes removed. Tangential radiotherapy fields were used to treat the breast. All patients were also treated with an abbreviated supraclavicular field with the lateral border medial to the humeral head. Pathological sections were available for review in 72 of the 82 women. RESULTS: Twenty-seven of 72 (37.5%) had evidence of ECE; 45 of 72 (62.5%) had metastatic carcinoma confined within the nodal capsule. Clinical characteristics were comparable between the patients with and without ECE with the exception of (a) pathologic subtype, with a greater percentage of infiltrating ductal tumors associated with ECE (p = 0.044), and (b) number of positive lymph nodes, with 93% of patients without ECE having one to three positive nodes vs. only 56% among patients with ECE (p < 0.001). With a median follow-up of 40 months, 1 of 27 patients (4%) with ECE experienced an axillary failure as a component of first failure compared to 0 of 45 patients without ECE (p = 0.4). There were no isolated axillary failures. Five-year disease-free survival (72% without ECE vs. 57% with ECE, p = 0.12) and overall survival (83% vs. 53%, respectively, p = 0.068) suggested a less favorable outcome for patients with ECE. CONCLUSIONS: Microscopic ECE appears to be associated with increased axillary involvement and decreased survival rather than subsequent axillary failure. Our data suggest that radiotherapy to a dissected axilla may be omitted for the sole indication of microscopic extracapsular disease.

Axilla↗

PubMed2004

The use of cytogenetics in understanding ovarian cancer.

The future of cancer research is no longer limited to epidemiological data and clinical management, but rather encompasses a new dimension of understanding, that involves genetics of the tumors themselves. This has been exemplified most prominently in hematological tumors where alterations at the DNA level have been found to play key roles in the pathophysiology, diagnosis, monitoring and prognosis of these tumors. It has been shown over the last 20 years that recurrent chromosomal rearrangements are strongly associated with the activation of oncogenes, acquisition of drug resistance and loss of tumor suppressor gene function. Chromosomal alterations have also been shown to characterize many solid tumors, including epithelial ovarian cancer [Cancer Res. 62 (2002) 3466; Cancer 91 (2001) 534; Genes Chromosomes Cancer 25 (1999) 290]. Despite these findings, however, there are currently few examples of specific cytogenetic studies that have contributed to the clinical management of solid tumors such as ovarian cancer. The limiting factor to date is the resolution of available techniques. With time, as the technology improves, so will our ability to focus on specific findings that may be applicable to future clinical management. The intention of this report is to familiarize the reader with the evolution of cytogenetic and molecular cytogenetic techniques used in the study of ovarian cancer, the early formulations from these studies and their use in answering specific clinical questions such as association with pathologic subtype, the relevance of drug resistance, the impact of BRCA mutations, and finally to guide the reader into the future of this ever growing field.

Animals↗

PubMed2006

Plasmacytoid urothelial carcinoma of the urinary bladder report of seven new cases.

INTRODUCTION: Plasmacytoid urothelial carcinoma (PUC) is a rare tumor of the urinary bladder. Its clinical and histopathological features have not been well characterized. In this study we report seven cases of PUC from our institution. MATERIALS AND METHODS: A pilot case of PUC was recently diagnosed at our institution. Cases of urothelial carcinoma (UC) were reviewed for a period of seven years to identify PUC. Representative sections from each case of PUC were submitted for immunohistochemical studies. Clinical charts were reviewed. RESULTS: There were a total of seven cases of PUC out of 260 cases of invasive urothelial carcinoma. The common type of urothelial carcinoma (CUC) was present in focal areas in five cases. Cases with extensive PUC showed coarse and indurated mucosal folds and thickened bladder walls, with no grossly identifiable tumor. Urine cytology showed a scant number of atypical single cells, frequently without tumor diathesis, leading to a shortfall in the positive cytological diagnosis. Histologically, PUC appeared as dyscohesive, plasmacytoid cells with eccentric nuclei, extending widely into the bladder walls and extensively into adjacent pelvic organs. CONCLUSION: PUC is a distinct clinical and pathological subtype of urothelial carcinoma. The clinical presentation is frequently late due to the frequent absence of hematuria and indurated mucosal surface at cystoscopy. The disease followed an ominous course with recurrence in all the patients, and with patient death.

Aged↗

PubMed2006

The role of postoperative radiation therapy in carcinoma ex pleomorphic adenoma of the parotid gland.

PURPOSE: To evaluate the impact of postoperative radiation therapy on the clinical course of patients with carcinoma ex pleomorphic adenoma of the parotid gland. METHODS AND MATERIALS: Between 1960 and 2004, 63 patients were treated with definitive surgery for carcinoma ex pleomorphic adenoma of the parotid gland. Forty patients (63%) received postoperative radiation therapy to a median dose of 60 Gy (range, 45-71 Gy). Adenocarcinoma (29 patients), salivary duct carcinoma (16 patients), and adenoid cystic carcinoma (9 patients) were the most common malignant subtypes. Pathologic T -stage was: 16% T1, 33% T2, 32% T3, and 19% T4. Twenty-one patients (33%) had microscopically positive margins and 39 (62%) had perineural invasion. Median follow-up was 50 months (range, 2-96 months). RESULTS: The use of postoperative therapy significantly improved 5-year local control from 49% to 75% (p = 0.005) and was associated with an improvement in survival among patients without evidence of cervical lymph node metastasis (p = 0.01). A Cox proportional hazard model identified pathologic involvement of cervical lymph nodes as an independent predictor of overall survival. Overall survival was 16% for patients with pathologic N-positive disease compared with 67% for those whose lymph node status was negative or unknown (p = 0.001). CONCLUSION: Surgery followed by postoperative radiation should be considered the standard of care for patients with carcinoma ex pleomorphic adenoma.

Adenocarcinoma↗