Prospective assessment of white matter integrity in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05).There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT.

A prospective evaluation of changes in brain structure and cognitive functions in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is an efficacious treatment for many hematologic malignancies. However, the conditioning regimen of high-dose (HD) chemotherapy with or without total body irradiation (TBI) can be associated with neurotoxicity. In this prospective study, we used quantitative neuroimaging techniques to examine regional gray matter and ventricular volumes, and standardized neuropsychological tests to assess cognitive function before and 1 year after HSCT in 28 patients with hematologic malignancies and in ten healthy controls evaluated at similar intervals. Nineteen patients received conditioning treatment with HD chemotherapy alone and nine had both TBI and HD chemotherapy. There was a significant reduction in gray matter volume in the middle frontal gyrus bilaterally and in the left caudate nucleus in the patient group (all patients combined) but not among healthy controls over the 1-year follow-up period. There was a significant increase in left lateral ventricle volume and in total ventricle volume in the patient group, relative to healthy controls. Similar brain structural changes were seen for patients treated with HD chemotherapy alone. The neuropsychological results showed that 21% of patients could be classified as impaired at baseline. The Reliable Change Index suggested no significantly different rates of cognitive decline between patients and healthy controls. The findings suggest that HSCT patients may be at an increased risk for developing regional brain volume loss, and that subgroups may experience cognitive dysfunction prior to and 1 year following the transplant.

Lactate MRSI and DCE MRI as surrogate markers of prostate tumor aggressiveness.

Longitudinal studies of lactate MRSI and dynamic contrast-enhanced MRI were performed at 4.7 T in two prostate tumor models grown in rats, Dunning R3327-AT (AT) and Dunning R3327-H (H), to determine the potential of lactate and the perfusion/permeability parameter Ak(ep) as markers of tumor aggressiveness. Subcutaneous AT (n = 12) and H (n = 6) tumors were studied at different volumes between 100 and 2900 mm(3) (Groups 1-5). Lactate concentration was determined using selective multiple quantum coherence MRSI with the phantom substitution method. Tumor enhancement after the administration of gadolinium diethylenetriaminepenta-acetic acid was analyzed using the Brix-Hoffmann model and the Ak(ep) parameter was used as a measure of tumor perfusion/permeability. Lactate was not detected in the smallest AT tumors (Group 1; 100-270 mm(3) ). In larger AT tumors, the lactate concentration increased from 2.8 ± 1.0 mm (Group 2; 290-700 mm(3)) to 8.4 ± 2.9 mm (Group 3; 1000-1340 mm(3)) and 8.2 ± 2.2 mm (Group 4; 1380-1750 mm(3) ), and then decreased to 5.0 ± 1.7 mm (Group 5; 1900-2500 mm(3)), and was consistently higher in the tumor core than in the rim. Lactate was not detected in any of the H tumors. The mean tumor Ak(ep) values decreased with increasing volume in both tumor types, but were significantly higher in H tumors. In AT tumors, the Ak(ep) values were significantly higher in the rim than in the core. Histological hypoxic and necrotic fractions in AT tumors increased with volume from 0% in Group 1 to about 20% and 30%, respectively, in Group 5. Minimal amounts of hypoxia and necrosis were found in H tumors of all sizes. Thus, the presence of lactate and heterogeneous perfusion/permeability are signatures of aggressive, metabolically deprived tumors.

Cytogenetic and morphological abnormalities in paroxysmal nocturnal haemoglobinuria.

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by the expansion of a haematopoietic stem cell clone with a PIG-A mutation (the PNH clone) in an environment in which normal stem cells are lost or failing: it has been hypothesized that this abnormal marrow environment provides a relative advantage to the PNH clone. In patients with PNH, generally, the karyotype of bone marrow cells has been reported to be normal, unlike in myelodysplastic syndrome (MDS), another clonal condition in which cytogenetic abnormalities are regarded as diagnostic. In a retrospective review of 46 patients with a PNH clone, we found a karyotypic abnormality in 11 (24%). Upon follow-up, the proportion of cells with abnormal karyotype decreased significantly in seven of these 11 patients. Abnormal morphological bone marrow features reminiscent of MDS were common in PNH, regardless of the karyotype. However, none of our patients developed excess blasts or leukaemia. We conclude that in patients with PNH cytogenetically abnormal clones are not necessarily malignant and may not be predictive of evolution to leukaemia.

Pap smears in women with endometrial carcinoma.

OBJECTIVE: To correlate Pap smear findings with the histology of endometrial carcinoma and stage of the disease. STUDY DESIGN: Between 1995 and 1998, 76 women with endometrial carcinoma, having had Pap smears done within two to three months of hysterectomy at Memorial Sloan-Kettering Cancer Center, formed the basis for this study. All Pap smears and histologic sections were reviewed. RESULTS: Thirty-four patients had normal Pap smears (45%), and 42 had abnormal ones (55%). The mean age of the two groups was 65.1 and 65.2 years, respectively. Histologic subtypes included 44 International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrioid adenocarcinoma (low grade) and 32 high grade carcinomas, including 19 FIGO grade 2 or 3 endometrioid adenocarcinomas, 5 papillary serous carcinomas (PSC), 2 clear cell carcinomas (CC), 1 adenosquamous carcinoma, 3 endometrioid adenocarcinomas mixed with PSC and 2 endometrioid adenocarcinomas mixed with CC. The proportions of patients with low and high grade tumors with abnormal Pap smears were 43% (19/44) and 72% (23/32), respectively (P=.01). The proportions of patients with abnormal Pap smears and no myometrial invasion, invasion of <50% and >50% myometrial thickness were 40% (8/20), 62% (26/42) and 57% (8/14), respectively (P =.27). Vascular invasion was identified in 56% (9/16) of patients with abnormal Pap smears and in 55% (33/60) of patients with normal ones (P = .93). The proportions of patients having abnormal Pap smears with stage I and stages II, III or IV disease were 48% (30/62) and 86% (12/14), respectively (P =.01). CONCLUSION: Although the Pap smear is not a sensitive screening test for endometrial cancer and a negative Pap smear does not rule it out, this study revealed that abnormal Pap smears are significantly associated with high grade of tumor and stage II-IV endometrial carcinoma. However, they are not associated with patient age, depth of myometrial invasion or vascular invasion.

Limitations of family cancer history assessment at initial surgical consultation.

PURPOSE: Although important for the diagnosis of familial clustering of colorectal cancer and hereditary nonpolyposis colorectal cancer, the accuracy of familial cancer history assessment in the office setting has been questioned. Furthermore, there are few publications describing the optimal method for accurately capturing a family cancer history. The purpose of this study was to determine how well family cancer history is assessed in patients with early age-of-onset colorectal cancer at initial surgical consultation compared with a telephone interview and mailed questionnaire. METHODS: Medical records of patients 40 years old or younger at the time of colorectal cancer surgery were reviewed for documentation of family cancer history at initial surgical consultation. In addition, family cancer history was solicited from surviving patients or their next of kin by telephone and a mailed questionnaire. The kappa coefficient was used to measure degree of correlation between family cancer history obtained at initial surgical consultation and subsequent telephone interview and questionnaire. RESULTS: One hundred twenty-five patients were available for analysis. Family cancer history was documented on the initial surgical consultation report in 78 percent of cases. Although 31.2 percent were identified as having no family cancer history at initial surgical consultation, this proportion decreased to 13.5 percent after telephone interviews and questionnaires. Family history assessment at initial surgical consultation also failed to identify 7 of 11 individuals meeting Amsterdam criteria for hereditary nonpolyposis colorectal cancer and 10 of 16 individuals meeting modified clinical criteria for hereditary nonpolyposis colorectal cancer. CONCLUSIONS: Although family cancer history was commonly obtained during the initial surgical consultation of patients with colorectal cancer, there was a tendency to underestimate the extent of familial cancer. A telephone interview and questionnaire conducted at a later date may reveal a more comprehensive family cancer history. This is an important observation, because individuals identified as high-risk for hereditary nonpolyposis colorectal cancer or familial clustering of colorectal cancer require special consideration with respect to screening, surveillance, and surgical management.

Selective loss of KGDHC-enriched neurons in Alzheimer temporal cortex: does mitochondrial variation contribute to selective vulnerability?

THE RESEARCH OBJECTIVE: of this study was to test whether variation in mitochondrial composition is associated with "selective vulnerability" in Alzheimer brain. The term "selective vulnerability" refers to the loss of relatively vulnerable brain cells and the sparing of relatively resistant brain cells in disorders in which a genetic defect or environmental agent acts on both types of cells. The mechanisms underlying selective vulnerability are largely unknown, but mitochondria may be involved; the composition of mitochondria varies among different types of neurons, and mitochondria have an important role in cell death. Alzheimer's Disease (AD) is one of a number of neurodegenerative disorders in which both selective vulnerability and abnormalities of mitochondria occur. METHODS: We examined by immunohistochemistry the cellular distribution of a mitochondrial constituent (the alpha-ketoglutarate dehydrogenase complex, KGDHC) known to be deficient in AD, in relation to the known selective vulnerability of neurons in areas 21 and 22 of the temporal lobe in this neurodegenerative disorder. RESULTS: In normal human brain, cortical layers III and V contain neurons intensely immunoreactive for KGDHC, compared to other cells in these areas. The KGDHC-enriched cells are lost in AD (p < 0.001). In layer III, the loss of KGDHC-enriched cells is proportional to total loss of neurons, as determined by immunoreactivity to neuron specific enolase (NSE). In layer V, a higher proportion of the KGDHC-enriched neurons are lost than of other (NSE positive) neurons (p < 0.001). SIGNIFICANCE: Variations in mitochondrial composition may be one of the factors determining which cells die first when different types of cells are exposed to the same stress.

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo.

Suberoylanilide hydroxamic acid (SAHA) is the prototype of a family of hybrid polar compounds that induce growth arrest in transformed cells and show promise for the treatment of cancer. SAHA induces differentiation and/or apoptosis in certain transformed cells in culture and is a potent inhibitor of histone deacetylases. In this study, we examined the effects of SAHA on the growth of human prostate cancer cells in culture and on the growth of the CWR22 human prostate xenograft in nude mice. SAHA suppressed the growth of the LNCaP, PC-3, and TSU-Pr1 cell lines at micromolar concentrations (2.5-7.5 microM). SAHA induced dose-dependent cell death in the LNCaP cells. In mice with transplanted CWR222 human prostate tumors, SAHA (25, 50, and 100 mg/kg/day) caused significant suppression of tumor growth compared with mice receiving vehicle alone; treatment with 50 mg/kg/day resulted in a 97% reduction in the mean final tumor volume compared with controls. At this dose, there was no detectable toxicity as evaluated by weight gain and necropsy examination. Increased accumulation of acetylated core histones was detected in the CWR22 tumors within 6 h of SAHA administration. SAHA induced prostate-specific antigen mRNA expression in CWR22 prostate cancer cells, resulting in higher levels of serum prostate-specific antigen than predicted from tumor volume alone. The results suggest that hydroxamic acid-based hybrid polar compounds inhibit prostate cancer cell growth and may be useful, relatively nontoxic agents for the treatment of prostate carcinoma.

Peritoneal washings in endometrial carcinoma. A study of 298 patients with histopathologic correlation.

OBJECTIVE: To correlate findings of peritoneal washings in patients with endometrial carcinoma with histologic parameters. STUDY DESIGN: Between 1995 and 1998, 298 women with endometrial carcinoma were treated by hysterectomy with intraoperative peritoneal washings (PW) at Memorial Sloan-Kettering Cancer Center. All cytology and pathology slides were available for review. Pathologic parameters of hysterectomy specimens were evaluated and correlated with the findings of PW. RESULTS: Thirty-two patients (10.7%) had abnormal PW. Two hundred sixty-two had endometrioid adenocarcinoma; 26 of them had abnormal PW (10.0%). Thirty-six patients had other histologic subtypes (papillary serous carcinoma, clear cell carcinoma and adenosquamous carcinoma), and six of them had abnormal PW (16.7%). The incidence of abnormal PW in the two groups was not significantly different (P = .78). Among 26 patients with endometrioid adenocarcinoma and abnormal PW, there were 17 cases (9.9%) of International Federation of Gynecology and Obstetrics (FIGO) grade 1, 7 (12.7%) of grade 2 and 2 (5.7%) of grade 3 (P = .56). Ten cases (14.9%) had no myometrial invasion, 10 (7.0%) had myometrial invasion of < or = 50% of myometrial thickness, and 6 (11.5%) had invasion of > 50% of myometrial thickness (P = .18). Vascular invasion was present in 8 cases (14.8%) and absent from 17 (8.2%) (P = .14). Eighteen patients (7.6%) had stage I/II disease, and eight patients (30.8%) had stage III/IV disease (P = .001). Among 298 patients, cervicovaginal smears performed before surgery were available for review in 76. Five of the 7 patients (71.4%) with abnormal PW and 37 of the 69 patients (53.6%) with normal PW had abnormal Pap smears (P = .45). CONCLUSION: Abnormal PW did not correlate with histologic subtypes, FIGO grade, depth of myometrial invasion, vascular invasion or abnormal Pap smears. A significantly higher incidence of abnormal PW was associated with stage III/IV disease.

Abnormal T-cell repertoire is consistent with immune process underlying the pathogenesis of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of the hematopoietic stem cell (HSC). Somatic mutations in the PIG-A gene result in the deficiency of several glycosylphosphatidylinositol-linked proteins from the surface of blood cells. This explains intravascular hemolysis but does not explain the mechanism of bone marrow failure that is almost invariably seen in PNH. In view of the close relationship between PNH and idiopathic aplastic anemia (IAA), it has been suggested that the 2 disorders might have a similar cellular pathogenesis, namely, that autoreactive T-cell clones are targeting HSCs. In this paper, we searched for abnormally expanded T-cell clones by size analysis of the complementarity-determining region 3 (CDR3) in the beta variable chain (BV) messenger RNA (mRNA) of the T-cell receptor (TCR) in 19 patients with PNH, in 7 multitransfused patients with hemoglobinopathy. and in 11 age-matched healthy individuals. We found a significantly higher degree of skewness in the TCR BV repertoire of patients with PNH, compared with controls (R(2) values 0.82 vs 0.91, P <.001). The mean frequency of skewed families per individual was increased by more than 2-fold in patients with PNH, compared with controls (28% +/- 19.6% vs 11.4% +/- 6%, P =.002). In addition, several TCR BV families were significantly more frequently skewed in patients with PNH than in controls. These findings provide experimental support for the concept that PNH, like IAA, has an immune pathogenesis. In addition, the identification of expanded T-cell clones by CDR3 size analysis will help to investigate the effect of HSC-specific T cells on normal and PNH HSCs.

Reinfusion of mediastinal blood after heart surgery.

BACKGROUND: Several authors studying autotransfusion of shed mediastinal blood in patients undergoing heart operations have published conflicting results regarding reduction of the need for homologous blood transfusion. The effect on coagulation parameters is also unclear. METHODS: In a prospective randomized study, 198 patients who underwent coronary artery bypass grafting or a valvular operation were divided into 2 groups: a group with autotransfusion of shed mediastinal blood after an operation and a control group. Continuous reinfusion of mediastinal blood was done until no drainage was present or for a period of 12 hours after the operation. The amount of blood lost and autotransfused, the number of homologous blood products transfused, and the coagulation parameters were monitored. RESULTS: The number of patients requiring homologous blood transfusion was significantly different between the 2 groups (54/98 [55%] in autotransfused patients vs 73/100 [73%] in the control group, P =.01). The number of re-explorations for excessive bleeding was similar in the 2 groups (7/98 [7.1%] vs 8/100 [8%]), but the amount of blood collected postoperatively was higher in the autotransfused patients compared with control patients (1200 +/- 201 mL vs 758 +/- 152 mL, P =.0007). Coagulation parameters analyzed and complication rates were similar in the 2 groups after the operations. CONCLUSION: Autotransfusion of shed mediastinal blood reduces the need for homologous blood transfusion in patients undergoing various cardiac operations. The cause of increased shed blood in patients undergoing autotransfusion remains unclear.

The memorial symptom assessment scale short form (MSAS-SF).

BACKGROUND: The Memorial Symptom Assessment Scale Short Form (MSAS-SF), an abbreviated version of the Memorial Symptom Assessment Scale, measures each of 32 symptoms with respect to distress or frequency alone. A physical symptom subscale (PHYS), psychologic symptom subscale (PSYCH), and global distress index (GDI) can be derived from the Short Form. We validated the MSAS-SF in a population of cancer patients. METHODS: Two hundred ninety-nine cancer patients examined at the Section of Hematology/Oncology completed the MSAS-SF and the Functional Assessment Cancer Therapy (FACT-G). The Karnofsky performance status (KPS), extent of disease (EOD), and demographic data were assessed. The Cronbach alpha coefficient was used to assess internal reliability. MSAS-SF subscales were assessed against subscales of the FACT-G, the KPS, and EOD to determine criterion validity. Test-retest analysis was performed at 1 day and at 1 week. RESULTS: The Cronbach alpha coefficients for the MSAS-SF subscales ranged from 0.76 to 0.87. The MSAS-SF subscales showed convergent validity with FACT subscales. Correlation coefficients were -0.74 (P < 0.001) for the PHYS and FACT-G physical well-being subscales, -0.68 (P < 0.001) for the PSYCH and FACT emotional well-being subscales, and -0.70 (P < 0.001) for GDI and FACT summary of quality-of-life subscales. The MSAS-SF subscales demonstrated convergent validity with performance status, inpatient status, and extent of disease. The test-retest correlation coefficients for the MSAS-SF subscales ranged from 0.86 to 0.94 at 1 day and from 0.40 to 0.84 for the 1 week group. CONCLUSIONS: The MSAS-SF is a valid and easy to use instrument for symptom assessment.

Association between initial diagnostic procedure and hysteroscopy and abnormal peritoneal washings in patients with endometrial carcinoma.

BACKGROUND: Hysteroscopy has been implicated in the finding of positive peritoneal washings (PW) in patients with endometrial carcinoma in several case reports. The current study was designed to evaluate whether there was an increased incidence rate of positive peritoneal washings in patients after hysteroscopy compared with patients who did not undergo hysteroscopy. METHODS: Two hundred eighty-four women with endometrial carcinoma were treated by hysterectomy with intraoperative PW at the Memorial Sloan-Kettering Cancer Center between 1995-1998. They were diagnosed by either endometrial biopsy (EMB) or dilatation and curretage (D & C) with or without hysteroscopy during the same period. RESULTS: Of 173 patients diagnosed by EMB, 16 had abnormal PW (9.2%). Of 111 patients diagnosed by D & C, 11 had abnormal PW (9.9%). There was no significant difference between the two groups (P = 0.85). Of 23 patients who were diagnosed by D & C with hysteroscopy, 3 had abnormal PW (13.0%). Of 177 patients who did not undergo hysteroscopy, 17 had abnormal PW (9.6%). Of 84 patients for whom information regarding hysteroscopy was not available, 7 had abnormal PW (8.3%). The incidence rates among the three groups were not significantly different (P = 0.79). CONCLUSIONS: The initial diagnostic procedure, including hysteroscopy, does not appear to be associated with a high incidence rate of abnormal PW in patients with endometrial carcinoma.

The measurement of symptoms in children with cancer.

The purpose of this study was to determine symptom prevalence, characteristics, and distress in children with cancer. The Memorial Symptom Assessment Scale (MSAS) 10-18, a 30-item patient-rated instrument adapted from a previously validated adult version, provided multidimensional information about the symptoms experienced by children with cancer. This instrument was administered to 160 children with cancer aged 10-18 (45 inpatients, 115 outpatients). To confirm the instrument's reliability and validity, additional data about symptoms were collected from both the parents and the medical charts, and retesting was performed on a subgroup of inpatients. Patients could easily complete the scale in a mean of 11 minutes. The analyses supported the reliability and validity of the MSAS 10-18 subscale scores as measures of physical, psychological, and global symptom distress, respectively. Symptom prevalence ranged from 49.7% for lack of energy to 6.3% for problems with urination. The mean (+/- SD) number of symptoms per inpatient was 12.7 +/- 4.9 (range, 4-26), significantly more than the mean 6.5 +/- 5.7 (range, 0-28) symptoms per outpatient. Patients who had recently received chemotherapy had significantly more symptoms than patients who had not received chemotherapy for more than 4 months (11.6 +/- 6.0 vs. 5. 2 +/- 5.1), and those patients with solid tumors had significantly more symptoms than patients with either leukemia, lymphoma, or central nervous system malignancies (9.9 +/- 7.0 vs. 6.8 +/- 5.5 vs. 6.8 +/- 5.0 vs. 8.0 +/- 6.1). The most common symptoms (prevalence > 35%) were lack of energy, pain, drowsiness, nausea, cough, lack of appetite, and psychological symptoms (feeling sad, feeling nervous, worrying, feeling irritable). Of the symptoms with prevalence rates > 35%, those that caused high distress in more than one-third of patients were feeling sad, pain, nausea, lack of appetite, and feeling irritable. Subscale scores demonstrated large variability in symptom distress and could identify subgroups with high distress. The prevalence, characteristics, and distress associated with physical and psychological symptoms could be quantified in older children with cancer. The data confirm a high prevalence of symptoms overall and the existence of subgroups with high distress associated with one or multiple symptoms. Symptom distress is relatively higher among inpatients, children with solid tumors, and children who are undergoing antineoplastic treatment. Systematic symptom assessment may be useful in future epidemiological studies of symptoms and in clinical chemotherapeutic trials. Symptom epidemiology may also provide a focus for future clinical trials related to symptom management in children with cancer.

Surgical management of renal tumors 4 cm. or less in a contemporary cohort.

PURPOSE: We evaluated a patient cohort with renal tumors 4 cm. or less treated with partial or radical nephrectomy. We compared patient and tumor characteristics, and survival in these 2 groups. MATERIALS AND METHODS: We retrospectively analyzed the records of 670 patients with a median age of 63 years treated surgically for renal cell carcinoma between July 31, 1989 and July 31, 1997. Renal tumors 4.0 cm. or less were noted in 252 patients (38%) who underwent a total of 262 procedures, including 183 radical (70%) and 79 partial (30%) nephrectomies. Ten patients required 2 operations each because of bilateral renal cell carcinoma. Median followup was 40 months. We compared clinicopathological parameters in the partial and radical nephrectomy groups using chi-square or Wilcoxon analysis as appropriate. Survival analysis was determined by the log rank test and Cox regression model. RESULTS: The partial and radical nephrectomy groups were comparable with respect to gender ratio, tumor presentation, histological classification, pathological stage and complication rate. Median tumor size was 2.5 and 3.0 cm. in the partial and radical nephrectomy groups, respectively (p = 0.0001). Resection was incomplete in 1 patient (1.3%) in the partial and none in the radical nephrectomy group. There was no local recurrence after either procedure, and no significant difference in disease specific, disease-free and overall survival (p = 0.98, 0.23 and 0.20, respectively). CONCLUSIONS: Patients with a small renal tumor have similar perioperative morbidity, pathological stage and outcome regardless of treatment with partial or radical nephrectomy. Therefore, partial nephrectomy remains a safe alternative for tumors of this size.

Large cell non-Hodgkin lymphoma of childhood: Analysis of 78 consecutive patients enrolled in 2 consecutive protocols at the Memorial Sloan-Kettering Cancer Center.

BACKGROUND: The authors report a study of pediatric patients with advanced diffuse large cell lymphoma (DLCL) who were treated with 2 consecutive regimens, LSA2-L2 and LSA4, over a 25-year-period at the Memorial Sloan-Kettering Cancer Center. They also describe a comparative analysis of two subgroups retrospectively identified as having CD30 positive (+) anaplastic large cell lymphoma (ALCL) and CD30 negative (-) DLCL. To the authors' knowledge, this study represents the longest follow-up on the largest series of uniformly treated pediatric DLCL patients reported to date. METHODS: A total of 78 consecutive patients were treated for Stage III/IV DLCL. Immunophenotypic data were obtained retrospectively for 52 patients using a panel of monoclonal antibodies against CD30, CD15, CD45, CD45Ro, CD43, epithelial membrane antigen, CD5, BCL-2, cyclin-D, and p53. RESULTS: A disease free survival rate of 72% in patients with advanced stage DLCL using the LSA2-L2 and LSA4 regimens. Of the 78 treated patients, 56 are alive and without evidence of disease with a median follow-up of 120 months (range, 24-312 months). The recurrence rate was significantly higher in the CD30+ ALCL subgroup (33%) than in the CD30- DLCL group (0.04%). Of 52 patients for whom immunophenotypic data were available, 28 had disease of B-cell lineage, 24 had disease of T-cell/null phenotype, 19 were CD30+ (36. 5%), 18 had disease of T-cell phenotype, and 1 had disease of B-cell lineage. CONCLUSIONS: The CD30- DLCL cases mostly were of B-cell lineage, had a small risk of treatment failure, and did not develop a recurrence off therapy. A distinct clinical pattern was identified for the CD30+ ALCL group; although these tumors were of T-cell lineage and had a significantly higher rate of late recurrences (median follow-up of 24 months) they all were salvageable. Based on the findings of the current study, the authors propose that T-cell CD30+ ALCL be addressed in the future according to equal dose intensity regimens in induction therapy, as is done for B-cell lymphomas; prolonged periods of maintenance chemotherapy, as is done for T-cell lymphoblastic lymphomas; and no central nervous system prophylaxis beyond the induction period unless other recognized risk factors are present.

Favorable short-term and long-term outcome after elective radical rectal cancer resection in patients 75 years of age or older.

PURPOSE: Because the elderly population in Western countries is rapidly increasing, as is their life expectancy, studies aimed at determining the impact of major surgery for primary rectal cancer in this group are warranted. The purpose of this study was to compare perioperative morbidity and mortality and long-term disease-specific and overall survival in primary rectal cancer patients, older and younger than 75 years of age, subject to major pelvic surgery. METHODS: From September 1986 to December 1996, the Prospective Colorectal Service Database identified 1,120 consecutive patients who underwent major pelvic surgery for primary rectal cancer. Of these, 157 (15 percent) were 75 years of age or older and comprise the elderly group. From the remaining 963 patients younger than 75 years of age, a representative random sample of 174 was selected and constitutes the younger group. Data were obtained from computerized databases and confirmed via chart review and telephone interviews. RESULTS: Perioperative complications were observed in 53 (34 percent) elderly and 63 (36 percent; P = not significant) younger patients. Perioperative deaths occurred in two (1.3 percent) elderly and one (0.6 percent; P = not significant) younger patient. The median follow-up time was 48 months. Although the overall survival was lower in the elderly group (P = 0.02; the 5-year overall survival rates were 51 and 66 percent), the disease-specific survival rate was similar in the two groups (P = 0.75; the 5-year disease-specific survival rates were 69 and 71 percent). CONCLUSION: In select individuals 75 years of age or older, major pelvic surgery for primary rectal cancer can be done with perioperative morbidity and mortality rates comparable to those obtained in younger individuals, while achieving excellent disease-specific and overall long-term survival.

Patients' sensations after breast cancer surgery. A pilot study.

PURPOSE: The purpose of this study was to obtain information about the prevalence and characteristics of breast sensations after breast cancer surgery, the impact they had on patients, and aggravating and relieving factors. DESCRIPTION OF STUDY: Within 1 month after the date of their surgery, 132 patients with breast cancer completed an instrument rating the prevalence, severity, and level of distress of breast sensations. Information also was obtained on the impact that those sensations had on activities of daily living and factors that triggered and provided relief from sensations. RESULTS: Certain sensations remain prevalent (numb, tender), severe (burning, sharp), and distressing (cramping, painful). Overall these sensations significantly interfered with patients' activities of daily living. Certain activities (movement, position change) triggered sensations, while others (position change, medication) provided relief. CLINICAL IMPLICATIONS: Healthcare professionals can use the information learned from this pilot study to educate patients both preoperatively and postoperatively about prevalent breast sensations after surgery for breast cancer and about the types of activities that may aggravate or relieve these sensations. As patient educators and advocates, oncology professionals must continue to explore the long-term effects and treatment options to provide optimal care and support to patients who have or are likely to have post-surgical breast sensations. More studies are needed to explore long-term effects and treatment options.

Adult brainstem gliomas.

OBJECTIVE: To evaluate prognostic factors and survival of adult patients with brainstem gliomas. BACKGROUND: Brainstem glioma is a disease found primarily in children, with a median survival of only 9 to 12 months. However, the prognosis and survival of adults with this disease has not been determined with precision. METHODS: We conducted a retrospective analysis of patients older than 16 years at Memorial Sloan-Kettering Cancer Center with histologically proved or presumed brainstem glioma diagnosed between 1989 and 1997. We assessed the effect of gender, age at diagnosis, cranial nerve involvement, duration of symptoms, exophytic component, MRI enhancement, site of disease, treatment, and Karnofsky performance status on survival. RESULTS: Twenty-three patients were identified, but complete information was available in only 19 (12 males and 7 females). Patients ranged in age from 17 to 70 years (median, 40 years). Twelve patients were treated with radiotherapy at diagnosis and seven were observed, three of whom received subsequent radiotherapy. Median survival is 54 months (range, 3 to 98 months) and the 5-year survival is 45%. There was a trend for patients with a higher performance status at diagnosis to have longer survival, but this did not reach statistical significance. Other factors did not affect survival. CONCLUSION: Adults with brainstem gliomas may survive significantly longer than children, suggesting the disease may be less aggressive in adults. Furthermore, some patients with a long duration of symptoms or tectal or cervicomedullary tumors may be managed initially with observation alone.

Quality of life and survival: the role of multidimensional symptom assessment.

BACKGROUND: Recent data from clinical trials suggest that quality-of-life (QOL) measurements may independently predict survival. The relation between survival and QOL measurements was tested among 122 inpatients and 96 outpatients with malignancies at one of four sites (colon, breast, ovary, or prostate) who participated in a cross-sectional validation study of the Memorial Symptom Assessment Scale (MSAS), a measure of the frequency of, severity of, and distress caused by physical symptoms. METHODS: The relation between MSAS summary scores and survival was evaluated in a multivariate analysis that adjusted concurrently for other important covariates, such as age, site and extent of disease, inpatient status, Karnofsky performance status (KPS), and other QOL measurements. RESULTS: In the multivariate analysis, extent of disease (P < 0.0001), inpatient status (P=0.014), higher MSAS physical symptom subscale score (P=0.004), and lower KPS score (P=0.009) independently predicted decreased survival. Other QOL measurements did not contribute significantly to the model. CONCLUSIONS: The MSAS physical symptom subscale score significantly predicts survival and adds to the prognostic information provided by KPS and extent of disease. Patients may be under-assessed regarding both the number and the severity of symptoms. Measurements of physical symptoms and related distress offer additional prognostic information concerning the survival of patients with cancer and may account for the predictive value of QOL scores.