A unique case of splenic marginal zone-cell lymphoma with synchronous clonal T-cell large granular lymphocyte proliferation: an immunologic,immunohistochemical and genotypic study

We describe a case of synchronous splenic marginal zone-cell lymphoma (SMZL) and T-cell large granular lymphocyte leukemia involving the spleen, liver, bone marrow and peripheral blood. The synchronous occurrence of these two processes was documented by morphological, immunophenotypical and molecular (PCR) analyses of all affected tissues. The pathogenetic mechanisms which may be responsible for the concomitant appearance of these two rather infrequent entities in the same anatomic sites are discussed.     

A feasibility study of 1-h paclitaxel infusion in patients with solid tumors

 The optimal schedule for paclitaxel administration has not yet been determined. This phase I/II study was carried out to evaluate the safety of paclitaxel administration by 1-h infusion in the outpatient setting. A total of 43 patients with advanced pretreated malignancies (18 breast, 18 ovarian, and 7 non-small-cell lung cancers) received at least 2 cycles of paclitaxel given at 175 mg/m² in a single dose by 1-h i. v. infusion. This protocol was repeated every 21 days. All patients were premedicated as follows: promethazine given i. m. at 50 mg, dexamethasone given at 16 mg in 250 ml normal saline by i. v. infusion for 20 min and ranitidine given i. v. at 50 mg in 250 ml normal saline over 15 min, all premedication being carried out 1 h before the paclitaxel infusion. In a total of 156 cycles, only 1 patient presented with a hypersensitivity reaction (grade 2 urticaria in 1 cycle) and another patient developed transient facial flushing (in 1 cycle; this was resolved by slowing of the infusion rate) on this schedule of paclitaxel administration. Other adverse side effects were usually mild and well tolerated. Alopecia was universal; myelosuppression was uncommon because our patients were supported with granulocyte colony-stimulating factor (G-CSF, lenograstim) given at 34 IU/day in the presence of a neutrophil count of <500 μl; neutropenia was seen in 50/156 (32%) cycles and was mild. Neurotoxicity was the most serious adverse effect, and all patients experienced mild to severe neuromuscular toxicity, mainly in the form of peripheral sensorimotor neuropathy and myalgias. In conclusion, 1-h paclitaxel administration is safe and reduces the duration of treatment, making its use more convenient and easy in the outpatient setting. A prospective comparison of 1-h versus 3-h paclitaxel infusion in terms of efficacy and toxicity is the subject of our current randomized study. Received: 29 September 1996 / Accepted: 26 January 1997     

Oxaliplatin plus high-dose leucovorin and 5-fluorouracil in pretreated advanced breast cancer: a phase II study.

BACKGROUND: The purpose of this study was to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes. PATIENTS AND METHODS: Fifty anthracycline- and taxane-pretreated MBC patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion on day 1, LV 200 mg/m(2)/day as a 2-h infusion followed by bolus 5-FU 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. RESULTS: The median age was 51 years (range 34-75). Twenty patients (40%) had received three or more chemotherapeutic regimens, 64% had three or four metastatic sites and 78% had visceral metastases. All patients had prior exposure to anthracyclines and taxanes. Based on an intention-to-treat analysis, one patient (2%) achieved a complete response and 16 (32%) a partial response, for a 34% overall response rate. Twenty-one patients (42%) had stable disease and 12 (24%) progressive disease. The median time to tumor progression was 5.3 months (range 0.5-12.8) and the median overall survival was 12.3 months (range 0.5-19.2). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 32% and 18%, respectively. Febrile neutropenia was experienced by three patients (6%), who were successfully treated. Grade 3/4 neurotoxicity was reported in 14% of the patients and gradually declined after treatment discontinuation. Cycle delays were reported in 28% of patients and dose reductions in 26%. Alopecia, nausea-vomiting, diarrhea and mucositis were not significant. There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin plus 5-FU/LV seems to be an active regimen in patients with MBC and prior exposure to anthracyclines and taxanes with a good safety profile. The incidence of severe toxicity was quite low and the compliance of patients to the treatment was satisfactory. The results obtained with this regimen could be considered encouraging in this heavily pretreated group of breast cancer patients with a high incidence of visceral metastases.     

Long-term results of various therapy concepts in severe pilon fractures

Introduction Intra-articular fractures of the tibia plafond are among the most challenging of orthopaedic problems. This is a retrospective case-control study of surgically treated pilon fractures which was undertaken to compare the internal fixation with the two external fixation methods. Methods This is a case-control study of 55 patients with 55 pilon fractures. There were 36 type C and 19 type B. Of these fractures, 24 were open and 31 closed. Three surgical protocols were used. In 20 patients, Group A, a half pin external fixator with ankle spanning was performed. The mean age of patients was 42.0 years (22.0–74.0), SD 14.1 and the mean follow-up was 77.7 months (38.0–132.0), SD 25.4. In 22 patients, Group B, a single ankle sparring ring hybrid external fixator under a small arthrotomy was performed. The mean age of patients was 48.4 years (28.0–76.0), SD 12.4 and mean follow-up was 67.9 months (36.0–132.0), SD 27.8. In 13 patients, Group C, a two-staged internal fixation was performed. The mean age was 45.6 years (30.0–66.0), SD 9.7 and the mean follow-up was 78.6 months (55.0–132.0), SD 25.4. We addressed the dissimilarity of the type of fracture in each group performing supplementary stratified analyses within each fracture type group. Results Group A had union in 6.9 months, group B in 5.6 months and group C in 5.1 months; P = 0.009. Six patients (Group A), two (Group B), and one (Group C) had limitation of ankle motion; P = 0.47. One patient from group C developed infection and the plate was removed. Four patients (Group A), one (Group B), and one (Group C) have developed posttraumatic arthritis (loss of joint space and pain); P = 0.25. Seven patients from Group A have reduced their activities; P = 0.004. In stratified statistical analysis by type of fracture, the associations noted for both fracture groups combined were also noted separately within each fracture group. Conclusion In this long term follow-up study, the two-staged internal fixation and the hybrid fixation with small arthrotomy were equally efficacious in achieving bone union. Patients in external fixation with the ankle spanning had a significantly higher rate of delayed union. Also more patients in this group have reduced their activities. Meeting at which the paper was presented: International Annual Meeting Of Orthopaedic Surgeons, 2003, Greece.     

Urine neutrophil gelatinase-associated lipocalin to predict acute kidney injury in preterm neonates. A pilot study

Background

The efficacy of urine neutrophil gelatinase-associated lipocalin (uNGAL) as an early acute kidney injury (AKI) biomarker in preterm neonates was evaluated.

Methods

Thirty-five preterm neonates were prospectively evaluated for serum creatinine (sCre)-documented AKI during the first 14 days of life. Urine samples were collected daily throughout the study period. Of the neonates evaluated, we analyzed 11 who developed AKI (cases) and an equal number of neonates without AKI (controls) matched for gestational and postnatal age (case–control study). uNGAL was measured on the day of AKI occurrence (day 0) and on the 2 days preceding the event (day ?1 and day ?2, respectively) using an enzyme-linked immunosorbent assay.

Results

Cases had significantly higher sCre levels than controls on day 0 (1.21?±?0.48 vs. 0.83?±?0.16 mg/dL, p?=?0.031) but not on days ?1 and ?2. Similarly, uNGAL levels (ng/mL) were significantly higher in cases than in controls only on day 0 (19.1?±?3.5 vs. 13.3?±?7.3, p?=?0.017) and not on days ?1 (18.8?±?3.4 vs. 16.3?±?5.9, p?=?0.118) and ?2 (19.3?±?1.8 vs. 19.4?±?0.8, p?=?0.979). The receiver operating characteristic curve analysis showed no significant ability of uNGAL to predict AKI on days ?2 and ?1.

Conclusions

In this pilot study in preterm neonates, although uNGAL detected sCre-based AKI upon its documentation, it failed to predict its development 1–2 days earlier.     

Indication for Liver Transplantation in Young Patients with Small Intestinal NETs Is Rare?

Background

A majority of patients with small intestinal neuroendocrine tumors (SI-NETs) present with or develop liver metastases (LM). A number of treatments for LM are used clinically, including liver transplantation (LTx). Indications for LTx are under debate; young age (<65 years), absence of extrahepatic disease, resected primary tumor and limited extent of LM have been suggested as inclusion criteria for LTx with the aim to optimize outcome.

Materials and methods

From our series of 672 patients with SI-NET treated at the University Hospital in Uppsala between 1985 and 2012, we identified 78 patients according to the following criteria: <65 years of age, locoregional surgery (LRS) of the primary tumor and mesenteric metastases successfully performed, LM present but no extrahepatic disease. Baseline was chosen as the first date the following points were met: First visit to our center, LRS performed, LM present. The patients underwent treatment according to the standard clinical protocols at our center, and during this time period we did not perform or refer any SI-NET patients for LTx. Kaplan–Meier survival analyses were performed in three different groups based on hypothetical criteria for LTx.

Results

Five-year overall survival rates for patients <65 years (n = 78) and <55 years (n = 36) of age were 84 ± 8 and 92 ± 9 %, respectively. For patients fulfilling the Milan criteria (n = 33) the 5-year survival was 97 ± 6 %.

Conclusions

Most young patients (<65 years) with SI-NET and LM have a favorable survival with standardized multimodality treatment. Indeed, most survival figures reported after LTx of NET do not surpass these figures.     

Predictors of anxiety in family caregivers*

The present study builds on the foundation laid in caring for family caregivers of dependent elderly persons through psycho-educational support. After briefly tracing the development of the programme and its associated evaluation research, an investigation of sociodemographic variables as predictors of caregivers' anxiety is described. In line with previous literature on caregiver stress, it was found that 461 caregivers' pretreatment negative emotional responses were closely related to high levels of anxiety in their particular situations. Less expected were the findings that length of caregiving, relationship to caregiver of care-recipient, residential arrangements, age of caregiver and disability of care-recipient did not contribute significantly to the regression analysis. Even more remarkable was the finding that the strongest predictors of anxiety were the combined factors of masculine gender, unemployment and involvement in fewer than the median number of caregiving responsibilities. Implications and recommendations for research and practice are drawn.