The role of intratumoral therapy with cisplatin/epinephrine injectable gel in the management of advanced squamous cell carcinoma of the head and neck

OBJECTIVE: To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck. DESIGN: Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression. SETTING: Tertiary referral centers in North America and Europe. PATIENTS: One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck. INTERVENTION: Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire. MAIN OUTCOME MEASURES: Local tumor response and patient benefit attributable to improvements in tumor-related symptoms. RESULTS: Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P<.001). Tumor response and patient benefit were significantly correlated (P=.006): 47% (17/36) of patients with target tumor responses achieved a rigorously defined benefit based on a prospectively selected treatment goal vs 15% (22/142) of nonresponders. CONCLUSION: Cisplatin/epinephrine injectable gel reduces tumor burden, ameliorates tumor symptoms, and provides a new therapeutic option for treating patients with squamous cell carcinoma of the head and neck.     

An examination of perceived stress in family caregivers of older adults with heart failure

This investigation evaluates the moderating influence of social support on the negative effects of stress for family caregivers and validates the Perceived Stress Scale as a standard of measurement. Seventy-five family caregivers to older adults with heart failure were interviewed in their homes about perceived stress, depressive symptoms, and social support after hospital discharge. The Perceived Stress Scale demonstrated internal consistency. Social support did not moderate the effects of stress on depressive symptoms. Lack of a significant association between salivary cortisol and the Perceived Stress Scale did not support testing of construct validity. Stress levels, however, frequently vary due to caregiving demands and additional influencing factors.     

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.     

CD30+ anaplastic large-cell lymphoma with aberrant expression of CD13: case report and review of the literature

CD13 is commonly expressed in hematopoietic malignancies of myelomonocytic origin and has less commonly been described in lymphoid neoplasms, including acute lymphoblastic leukemia, B-cell lymphoproliferative disorders, and plasma cell malignancies. Aberrant CD13 expression has rarely been described in KP-1 (CD68)-positive large-cell lymphomas. However, CD13 positivity has not previously been described in a case of CD30+ (ALK-1+) anaplastic large-cell lymphoma of presumed null-cell origin without histiocytic differentiation. The purpose of this case report is to describe a CD30+ anaplastic large-cell lymphoma of presumed null-cell origin with aberrant expression of CD13. The case illustrates the unique usefulness of immunophenotypic and molecular techniques in establishing the correct diagnosis. The case was referred with a diagnosis of "rule out granulocytic sarcoma versus megakaryocytic malignancy" due to the morphology and a limited flow cytometric immunophenotypic (FCI) panel that had been performed and revealed expression of CD45, HLA-DR, and CD13. Subsequent morphologic review at our institution combined with an expanded FCI panel established the diagnosis. The differential diagnosis of a CD13+ hematopoietic malignancy should include this entity. The prognostic significance of this finding has yet to be determined.     

Mantle cell leukemia, prolymphocytoid type: a rarely described form

Leukemic manifestations of mantle cell lymphoma are seen in a minority of cases, usually associated with extensive tumor. Usually the neoplastic cells in the peripheral blood resemble mantle cells with a mature chromatin pattern and irregular nuclear contours, or less frequently with a more "blastic" chromatin pattern. A prolymphocytic leukemia with t(11;14)(q13;q32) has previously been reported; however, a complete flow cytometric immunophenotypic profile was lacking. Mantle cell leukemia, prolymphocytoid type with complete flow cytometric data has not previously been described and is the purpose of this report. We report such a case in a 90 year-old female who presented with an elevated white blood cell count. The diagnosis was based on flow cytometric immunophenotyping and the cytomorphology of the peripheral blood combined with cyclin D1 immunohistochemical staining of the bone marrow. We describe our findings and her clinical course in order to heighten awareness of this previously rarely described entity.     

Paraffin immunoreactivity of CD10, CDw75, and Bcl-6 in follicle center cell lymphoma

Follicle center cell lymphoma(FCCL) has the following immunophenotype(IP): sIg+, Pan B+, CD10+/-, CD5-, CD23-/+, CD43-, CD11c-, CD25-. In addition, reactivities of a malignant lymphoma with CDw75(LN-1) and bcl-6 are considered indicators of FCCL. Bcl-6 expression is common in Grade 1 FCCL (100%) and rare in other indolent B-cell lymphomas(BCL). In contrast, bcl-2 expression is common in FCCL (80%) and in other BCL subtypes. Since no previous study has correlated paraffin immunoreactivity(PIR) of CD10, CDw75, and bcl-6 in FCCL (Grades 1-3), this is this study's purpose. Twenty-nine FCCL's were identified and reviewed (6, Grade 1; 10, Grade 2; 13, Grade 3) from the Division of Hematopathology, St. Louis University. The diagnoses were based on morphology and immunohistochemistry(IH)(21 cases) +/- the flow cytometric IP(14 cases). The paraffin blocks were stained for CD10 (Novacastra, Vector Laboratories, Burlingame, CA), CDw75 and bcl-6 (DAKO Corporation, Carpinteria, CA). Results showed that, CD10 by paraffin IH(PIH) was positive in 23 [18(strong); 3(moderate); 2(weak)] and negative in 6(3, Grade 2; 3, Grade 3). All CD10-cases were CDw75+; 4, bcl-6+. The two CD10-, bcl-6-cases were Grade 2. CDw75 was positive in 28 cases [16(strong); 11(moderate); 1(weak)] and negative in 1 (Grade 3; CD10+, bcl-2+, bcl-6+). Bcl-6 was positive in 26 [16(strong); 6(moderate); 4(weak)] and negative in 3(Grade 2's). Thus, the sensitivity of CD10, CDw75, and bcl-6 by PIH for FCCL was 79%, 97%, and 90%, respectively. Of the three stains evaluated by PIH in FCCL, CDw75 was the most sensitive, closely followed by bcl-6. CD10 was least sensitive-79%. By combining these 3 stains, the sensitivity was 100%; thus, a combined approach is recommended.     

Immunosuppressive and immunomodulatory therapy-associated lymphoproliferative disorders

A variety of therapeutic agents may increase the risk of lymphoproliferative disorders/neoplasms. These include those agents used to treat other malignancies (i.e., cytotoxic chemotherapy) and those used to treat or prevent certain diseases (or graft rejection) that alter the immune system. This review is restricted to the secondary lymphoid disorders that are unrelated to primary DNA damage by cytotoxic chemotherapy, and thus will include discussions regarding post-transplant lymphoproliferative disorders and those lymphoproliferations associated with the therapy of autoimmune and other immune-mediated diseases. Three drugs, or classes of drugs, used in the treatment of autoimmune and other immune-mediated diseases are discussed in some detail. These include methotrexate, anti-metabolites (including thiopurines and mycophenolate mofetil), and immunomodulators. The appropriate recognition of these disorders is important in order to correctly classify and institute appropriate therapy, recognizing that reduced immunosuppression or withdrawal of therapy may be necessary, rather than treating as a malignant lymphoma.