Subconjunctival Dirofilaria repens infection in a dog resident in the UK.

Dirofilaria repens infection was diagnosed in a 5-year-old female German shepherd crossbreed, originally from Romania but brought into the UK in February 2014. The dog presented with conjunctivitis in March 2014 and then again 2 months later with additional ocular and nasal mucopurulent discharge. Bacterial cultures from the nasolacrimal duct were negative for bacterial growth. The case was referred in August 2014 for ophthalmic examination, which revealed abnormalities in both eyes, especially the left. They included mild palpebral conjunctival hyperaemia and marked follicular conjunctivitis, as well as a dorsonasal bulbar conjunctival mass. Serum biochemistry was unremarkable and a conjunctival biopsy taken from the dorsonasal bulbar conjunctival mass revealed eosinophilic/lymphoplasmacytic conjunctivitis. At re-examination, nematodes were found in the area of the previous biopsy site and in the ventral palpebral conjunctival fornix. Polymerase chain reaction and sequencing confirmed these to be D. repens. Treatment with 10% imidacloprid and 2·5% moxidectin (Advocate Spot-On) was successful, and clinical signs resolved over a 6-week period. This case report indicates that D. repens infection should be considered as a possible aetiological cause of ocular lesions in dogs in the UK, especially those with a history of foreign travel. Implications for establishment and spread of D. repens in the UK are discussed.

Treatment and outcomes for glioblastoma in elderly compared with non-elderly patients: a population-based study.

PURPOSE: Elderly patients make up a large percentage of the individuals newly diagnosed with glioblastoma (gbm), but they face particular challenges in tolerating standard therapy, and compared with younger patients, they experience significantly shorter survival. We set out to compare clinical characteristics, treatment patterns, and outcomes in a non-elderly group (<65 years) and an elderly group (≥65 years) of patients diagnosed with gbm. METHODS: This retrospective population-based study used a province-wide cancer registry to identify patients with a new diagnosis of gbm within a 6-year period (2006-2012). Of the 138 patients identified, 56 (40.6%) were 65 years of age or older. Demographic characteristics, treatment patterns, and overall survival (os) in the elderly and non-elderly groups were compared. Predictors of os were determined using multivariate analysis. RESULTS: Elderly patients were more likely to present with a poor performance status (Eastern Cooperative Oncology Group ≥ 2), to undergo biopsy without resection, and to receive whole-brain or hypofractionated radiotherapy. Compared with non-elderly patients, the elderly patients were less likely to receive adjuvant temozolomide. Survival time was significantly shorter in the elderly than in the non-elderly patients (7.2 months vs. 11.2 months). In multivariate analysis, surgical resection, hypofractionated radiotherapy (compared with whole-brain or conventional radiotherapy), and chemotherapy were predictive of os in older patients. Among elderly patients receiving radiation, survival was improved with the use of combined therapy compared with the use of radiation only (11.3 months vs. 4.6 months). CONCLUSIONS: Overall survival was shorter for elderly patients with gbm than for non-elderly patients; the elderly patients were also less likely to receive intensive surgical or adjuvant therapy. Our population-based analysis demonstrated improved os with surgical resection, hypofractionated radiotherapy, and temozolomide, and supports the results of recent clinical trials demonstrating a benefit for combination chemoradiotherapy in older patients.

Using tablet-based technology in patient education about systemic therapy options for early-stage breast cancer: a pilot study.

BACKGROUND: Patient education in early-stage breast cancer has been shown to improve patient well-being and quality of life, but it poses a challenge given the increasingly complex regimens and time constraints in clinical practice. Technology-aided teaching in the clinic could help to improve the understanding of adjuvant systemic therapy for patients. In this prospective pilot study, we used a clinician-administered, tablet-based teaching aid to teach patients with early-stage breast cancer about adjuvant systemic therapy. METHODS: Participation was offered to newly diagnosed patients with early-stage breast cancer presenting for their first medical oncology visit at a provincial cancer centre. Participants were shown a tablet-based presentation describing procedures, rationales, risks, and benefits of adjuvant systemic therapy as an adjunct to a discussion with the medical oncologist. After the clinic visit, participants completed a questionnaire measuring satisfaction with the visit and knowledge of the treatment plan discussed. RESULTS: The 25 patients recruited for the study had a mean age of 57 years. An offer of upfront chemotherapy alone was made to 12 participants (48%), chemotherapy with trastuzumab to 4 (16%), and hormonal therapy to 9 (36%). Correct answers to all questions related to treatment knowledge were given by 22 patients (88%). Satisfaction with the clinic visit was high (mean satisfaction score: 4.53 ± 0.1 of a possible 5). CONCLUSIONS: We found that a tablet-based presentation about adjuvant systemic therapy was satisfactory to patients with early-stage breast cancer and that knowledge retention after the clinic visit was high. Tablet-based teaching could be a feasible and effective way of educating patients in the breast oncology clinic and warrants further investigation in randomized studies.

Prevalence, distribution and risk associated with tick infestation of dogs in Great Britain.

Current concerns over the potential impacts of climate change and the increased movement between countries of people and companion animals on the distribution of ectoparasites, highlight the need for accurate understanding of existing prevalence patterns. Without these future changes will not be detected. Here, the distribution and prevalence of tick infestations of domestic dogs in Great Britain were examined. A total of 173 veterinary practices were recruited to monitor tick attachment to dogs in their local areas between March and October 2009. Practices selected five dogs at random each week from those brought to the surgery and undertook a thorough, standardized examination for ticks. Each veterinary practice participated for 3 months before being replaced. Any ticks identified were collected and a sample sent to the investigators for identification, along with a clinical history of the dog. A total of 3534 dogs were examined; 810 dogs were found to be carrying at least one tick. Ixodes ricinus (Linnaeus) (Acari: Ixodidae) was identified in 72.1% of cases, Ixodes hexagonus Leach in 21.7% and Ixodes canisuga Johnston in 5.6% of cases. Five samples of Dermacentor reticulatus (Fabricius) (Acari: Ixodidae) were also found, adding to the growing evidence that an established population of D. reticulatus now exists in south-eastern England. Almost all the ticks found were adults. Overall, 19.2% of the veterinary practices reported no tick detections, 50% reported that ≥14.9% of the dogs seen were infested and 14.6% reported that >50% of the dogs inspected carried ticks. The estimated incidence of tick attachment was 0.013 per day in March (lowest) and 0.096 per day in June (highest). A number of risk factors affected the likelihood of tick attachment on dogs. Gundog, terrier and pastoral breed groups were more likely to carry ticks, as were non-neutered dogs. Dogs with shorter hair were less likely to have ticks, and dogs were most likely to carry a tick in June. This study is of value because, unusually, it presents the results of a randomized sample of dogs and gives a prevalence which is higher than those previously recorded in Great Britain.

Natural killer cell lymphoma: report of two pediatric cases, therapeutic options, and review of the literature.

BACKGROUND: Natural killer (NK) cell lymphomas are rapidly fatal malignancies that to the authors' knowledge are rare in children. In the current study, the authors report the cases of two boys with NK cell lymphomas with refractory disease who both were salvaged with high dose chemotherapy and stem cell transplantation and compare these patients with those in the published experience. METHODS: A comprehensive literature review was performed to identify other cases of pediatric patients with NK cell lymphomas, their treatment, and outcome. RESULTS: One of the patients in the current study developed two recurrences and the other patient experienced early disease progression during front-line treatment. Both then were treated with high dose chemotherapy followed by stem cell rescue. At last follow-up, the patients remained free of disease at 15 months and 16 months, respectively, after transplantation (48 months and 22 months, respectively, from the time of diagnosis). In addition to the 2 patients in the current study, the authors found 13 pediatric patients reported in the literature to date. Of the 7 patients with localized (Stage I-II) disease, 5 patients (71%) were reported to be alive 1-107 months after diagnosis. Of the 6 patients with Stage IV disease, only the 2 patients who received high dose chemotherapy and stem cell rescue (33%) were alive at the time of last follow-up (at 30 months and 12 months, respectively). Including the patients reported in the current study, 9 of 15 children with NK cell lymphoma (all stages) (60%) were reported to be alive at the time of last follow-up. CONCLUSIONS: Although pediatric NK cell lymphomas rapidly can become fatal, it appears that high dose chemotherapy followed by stem cell transplantation is effective therapy, especially in patients with advanced or resistant disease. Further follow-up is needed to determine whether this treatment approach will be curative.

Peripheral blood stem cell transplantation in young children: experience with harvesting, mobilization and engraftment.

The purpose of this study was to determine the feasibility and assess optimal timing of harvesting peripheral blood stem cells (PBSC) for transplantation in young children. Thirteen children with body weight less than 25 kg, mean age of 3.9 years (1-9 yrs) who had recurrent solid tumors and leukemia were given tumor specific chemotherapy followed by i.v. rhG-CSF (5 microg/kg/d) for stem cell mobilization. Cytaphereses were done through a central venous line (CVL) during the marrow recovery phase (WBC >0.5 x 10(9)/l). The phereses were analyzed separately and assigned to three groups depending on the WBC at the time of the pheresis: Group I (WBC <1.0 x 10(9)/l), Group II [WBC in the range 1.0-3.0 x 10(9)/l] and Group III (WBC >3.0 x 10(9)/l). Samples from each harvest were assayed for cell count, CFU-GM, BFU-E, CD34+ cell count, and tumor cell immunocytology in patients with neuroblastoma (NBL). A median of 3.2 x 10(8) mononuclear cells per kg (MNC/kg), [mean 2.8 x 10(8) MNC/kg, standard error of the mean (SEM) +/- 0.74 (1.1-4.7)] were infused following myeloablative therapy. 78 phereses were performed in 13 children with a median weight of 18 kg (10-25 kg). A median of 5 phereses were performed per patient. There were no significant differences in the percentage and number of CD34+ cells, CFU-GM or BFU-E colonies assayed by plating 0.5 x 10(5) cells. Differences could be found in the total number of MNC (p<0.008) and the number of MNC/kg (p<0.001) between Groups II and III. No tumor cell contamination was detected in the NBL patients by immunocytology. All patients were rescued with PBSC and achieved sustained white cell engraftment (ANC >0.5 x 10(9)/l) at a median of 13.5 d (10-25 d) and platelet engraftment (untransfused platelet count >20.0 x 10(9)/l) at a median of 29 d (12-63 d). The only toxicity encountered during the phereses was thrombocytopenia in 4 patients whose median post-pheresis platelet count was 6.0 x 10(9)/l (3.0-9.01). It is concluded that collection of PBSC in young children is feasible and safe and can be performed through a cuffed CVL at the time of WBC recovery post mobilization with chemotherapy and G-CSF. Cytopheresis can be effectively performed when the peripheral WBC count approaches 1.0 x 10(9)/l. Following stem cell infusion, engraftment was prompt and durable.

Treatment of poor-risk neuroblastoma patients with high-dose chemotherapy and autologous peripheral stem cell rescue.

A single institutional pilot study was conducted in which 12 poor-risk neuroblastoma (NB) patients were uniformly treated with multi-agent induction chemotherapy followed by myeloablative consolidation chemotherapy and unpurged peripheral blood stem cell (PBSC) rescue. In addition to using standard criteria for evaluating response to induction chemotherapy, tumor cell contamination of the peripheral blood and/or bone marrow was analyzed in seven patients by immunocytology using a panel of five anti-NB monoclonal antibodies. Seven patients had morphologic evidence of bone marrow disease at the time of diagnosis, and two additional patients had tumor cells detected in bone marrow samples by immunocytology prior to the second cycle of chemotherapy. After three cycles of chemotherapy, two of the 12 patients continued to have evidence of bone marrow disease. Samples from 29 PBSC harvests collected from nine patients were also analyzed for the presence of contaminating tumor cells by immunocytology. In each case, the stem cells were found to be free of tumor. Eleven of the 12 patients underwent myeloablative therapy and PBSC rescue; five patients remain alive without disease progression, 28+ to 53+ months from diagnosis, and six patients have developed recurrent disease. We conclude that PBSCs can be successfully harvested from children with NB, and used for hematopoietic reconstitution following myeloablative chemotherapy. However, more effective therapy for poor-risk NB patients is still urgently needed.

Haploidentical related umbilical cord blood stem cell transplant in a child with acute non-lymphocytic leukemia.

Umbilical cord blood stem cells (UCBSC) were used to reconstitute hematopoiesis following myeloablative therapy in a 13-month-old infant with acute nonlymphocytic leukemia (ANLL):FAB-M5 who had failed to sustain a chemotherapeutic remission. The patient's mother was 18 weeks pregnant with her second child at the time of diagnosis. Amniocentesis revealed that the fetus was HLA-haploidentical with the patient at the paternally inherited allele. The umbilical cord blood was harvested and processed by Ficoll centrifugation with 100% recovery of 5 x 10(7) mononuclear cells/kg and then cryopreserved. Two weeks after collection the cells were thawed and then infused into the patient following conditioning with total body irradiation, cyclophosphamide, and etoposide. Graft-versus-host-disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. The patient experienced clinical grade I GVHD consisting of skin involvement only that resolved within 2 weeks following the addition of corticosteroids. Engraftment was achieved with an absolute neutrophil count (ANC) above 0.5 x 10(9)/l on day 16, a platelet count above 50 x 10(9)/l on day 56, platelet transfusion independence on day 32 and red blood cell transfusion independence after day 44. Three months following transplantation restriction fragment length polymorphism (RFLP) revealed no discernible difference between the donor and the recipient. The patient remains in remission without evidence of GVHD 23 months post-transplant.

Serum erythropoietin levels in children with leukemia.

OBJECTIVE: Our aim was to test the hypothesis that, in leukemic children, serum erythropoietin (EPO) levels vary inversely with hemoglobin. DESIGN: Twenty-four children (15 males, nine females) with an age range of 1-16 years (mean, 7.7 years) diagnosed with acute leukemia (22 acute lymphocytic, two acute myeloid) were studied over 4 months. Serum EPO and hemoglobin were measured simultaneously at multiple time points in the course of their disease, and a multiple regression analysis was performed to describe the EPO-hemoglobin relationship. RESULTS: In a model adjusted for individual subject, there was a significant correlation between hemoglobin and logEPO in these leukemic children (r = -0.55, P < .01, n = 100). When measurements at hemoglobins less than 10.0 were analyzed the correlation increased significantly (r = -0.88, P < .01, n = 21). However, approximately 20% of the observations fell into one of two groups: an inappropriately low EPO for hemoglobin or an inappropriately elevated EPO for hemoglobin. The clinical characteristics of the children at each of these determinations were not different in any manner from the determinations which fell within the 95% confidence intervals for predicted mean EPO value: each of the outlying points came from a patient who at other times had an appropriate EPO for hemoglobin. CONCLUSIONS: There existed a significant inverse relationship between hemoglobin and EPO, suggesting that the feedback mechanism for EPO is intact. Reasons for inappropriately high or low EPO, for level of hemoglobin, are not clear and may be reflective of other aspects of bone marrow or EPO metabolism.

Prior fungal infection is not a contraindication to bone marrow transplant in patients with acute leukemia.

PURPOSE: Our aim was to assess the feasibility of bone marrow transplantation (BMT) in patients with acute leukemia who have had prior documented invasive fungal infection within 5 months pretransplant treated aggressively with systemic amphoteric in B and, when applicable, surgical resection of the infected tissue. MATERIALS AND METHODS: We reviewed the charts of patients with acute leukemia at our institution who underwent BMT between August 1992 and April 1994 after being treated for a severe fungal infection. We evaluated criteria for diagnosis of fungal infection, timing of infection in relation to BMT, and antifungal treatment modalities. We determined peritransplant complications, evidence for recurrence of fungal infection during BMT, morbidity related to antifungal drug therapy, and overall outcome in each patient. RESULTS: Fungal infection developed in eight patients. Sites of involvement included lung, liver, spleen, and skin. All patients were treated with systemic amphotericin B. Some also underwent surgical resection of infected tissue following clinical control of infection. All patients underwent BMT. Seven of eight patients engrafted and survived BMT. One patient died of recurrent pulmonary mucormycosis. Three patients are alive and free of leukemia and fungal disease. Four patients died of noninfectious causes and had no evidence of fungal disease at the time of death. CONCLUSIONS: Aggressive therapy of prior fungal infection followed by ongoing anti-fungal prophylaxis in acute leukemia patients may allow BMT without reactivation of the fungus. Reports of larger series of such patients as well as studies of the efficacy of chemoprophylaxis of fungal infections are needed.

Pyomyositis during induction chemotherapy for acute lymphocytic leukemia.

PURPOSE: Pyomyositis is a rare disease in temperate climate regions and frequently has a subacute presentation. Because of this, the entity is often misdiagnosed. PATIENTS AND METHODS: Two boys with acute lymphocytic leukemia (ALL) who presented with muscle pain, shortly after receiving induction chemotherapy, were evaluated. RESULTS: Presenting physical examination and laboratory findings were unremarkable except for extremity pain and tenderness. These symptoms were initially attributed to a neurotoxic side effect of vincristine. As the children's symptoms progressed, muscle abscess formation was finally delineated by gallium and computed tomography scans, and the diagnosis of pyomyositis was made. In both cases, the invading organism was Staphylococcus aureus. Both children responded well to incision and drainage of the abscesses and antibiotic therapy. CONCLUSION: Four cases of pyomyositis occurring in ALL patients shortly after induction chemotherapy have now been described. We feel that when children from this population present with muscle pain, pyomyositis should be part of the differential diagnosis. With early medical and surgical intervention, morbidity and mortality can be avoided.

Pancreatic blastomatous tumor in a child responding to therapy used for hepatoblastoma: case report and review of the literature.

A case is reported of a 7-year old girl diagnosed with initially inoperable metastatic embryonic pancreatic tumor, which showed a significant clinical response to chemotherapeutic agents commonly used to treat hepatoblastoma. This regimen was selected because certain histologic features of the tumor demonstrated characteristics seen in hepatic tissue. After two course of chemotherapy (cis-platinum and adriamycin), there was a significant reduction of the primary mass, and it was completely resected, although the tumor subsequently recurred in the metastatic, unoperated site. The embryological relationship between the tumor in this patient and hepatoblastoma, as well as the literature concerning treatment in pediatric pancreatoblastic tumors are reviewed. Complete eradication of tumor appears to be necessary for cure.

Prenatal detection of neuroblastoma by fetal ultrasonography.

PURPOSE: We report three cases of neuroblastoma diagnosed by prenatal ultrasound examination and examine the biologic features of tumors diagnosed prenatally. PATIENTS AND METHODS: Neuroblastoma is the most common tumor detected in the newborn period. Thus, some of these tumors develop prenatally and should be detectable by maternal ultrasound. Here we report three cases in which a neuroblastoma was suspected on prenatal ultrasonography. In addition, we review selected features of 17 additional cases reported in the literature. RESULTS AND CONCLUSIONS: These data indicate that, although the majority of patients have favorable clinical and biological features and do well, some patients do not, and the DNA index may be the most important predictor of outcome.

Renal functional reserve in long-term survivors of unilateral Wilms tumor.

We hypothesized that long-term survivors of unilateral Wilms tumor would have a decreased renal functional reserve secondary to the consequences of hyperfiltration in the nephrons of the remaining kidney. Therefore we evaluated the renal functional reserve in 12 long-term survivors of Wilms tumor after unilateral nephrectomy (mean +/- SE: 15 +/- 1.1 years; range 9 to 23 years). We measured the creatinine clearance before and after an acute, oral protein load to determine the renal functional reserve. Study subjects and control subjects were matched for age, gender, and body surface area. The basal creatinine clearances were similar (Wilms group 132 +/- 13 vs control group 142 +/- 11 ml/min/1.73 m2; p = not significant (NS]. There was no significant difference in the renal functional reserve between long-term survivors of Wilms tumor and matched control subjects (Wilms group 17 +/- 11 vs control group 25 +/- 11 ml/min/1.73 m2; p = NS). The change in creatinine clearance was not secondary to volume expansion because the fractional excretion of sodium was unchanged with protein loading (Wilms group before loading 0.92 +/- 0.12 vs after loading 0.99 +/- 0.13 (p = NS); control group before loading 0.91 +/- 0.12 vs after loading 1.0 +/- 0.14 (p = NS)). We conclude that up to 15 years after nephrectomy for unilateral Wilms tumor in childhood, there is no evidence of hyperfiltration injury.

Single copies of the N-myc oncogene in neuroblastomas from children presenting with the syndrome of opsoclonus-myoclonus.

Patients with neuroblastoma who present with the syndrome of opsoclonus and myoclonus enjoy a remarkably good prognosis independent of their stage of disease or their age at diagnosis. The presence of N-myc amplification also has been found to be an independent prognostic factor in neuroblastoma. Patients with multicopy N-myc tumors have rapid tumor progression whereas those with single-copy tumors have a significantly better progression-free survival. The authors examined four primary, untreated neuroblastomas for the N-myc copy number from patients who presented with opsoclonus and myoclonus. All four tumors had single copies of N-myc, and all four patients are alive with no evidence of recurrent disease with 6+ to 54+ months' follow-up. This appears to be the only report of N-myc analysis in this group of children. It would be interesting to analyze more neuroblastomas from patients who present with opsoclonus and myoclonus to determine how many of these patients have single N-myc copy tumors.

The spectrum of metabolic bone disease in lymphoblastic leukemia.

Eight patients with childhood acute lymphoblastic leukemia (ALL) and hypercalcemia, osteopenia, or vertebral compression fractures seen at our institution during the last 12 years were evaluated for biochemical evidence of bone disease. Five patients were hypercalcemic, three had abnormal phosphorous levels, and four had elevated alkaline phosphatase values. Parathyroid hormone (PTH) was measured by a polyvalent radioimmunoassay in five patients and these levels were abnormally high in three patients. Four of these five patients also had PTH measured by a midregion-specific radioimmunoassay. One patient had a high PTH value. Two patients had low levels and one patient had a normal PTH level. Although these studies suggest diverse biochemical mechanisms may be contributing to the bone changes and hypercalcemia seen in childhood ALL, ectopic PTH production as well as ectopically produced fragments of PTH may have a role in mediating bone resorption and hypercalcemia.

Enhancement of antigen expression on acute lymphoblastic leukemia (ALL) cells by cell incubation.

Leukemic cells from blood and/or marrow specimens of 64 acute lymphoblastic leukemia (ALL) patients were examined for the expression of the Ia-like antigen (Ia) or ALL cell-associated antigen (ALLA) employing indirect immunofluorescent techniques before and after overnight incubation (18 hours) at room temperature in Roswell Park Memorial Institute medium 1640. In 20 cases, the post-incubation cells showed an augmented intensity of the fluorescent stain and an increased (greater than 15%) percentage of the ALLA and/or Ia-bearing cells. Evaluation of cell viability after incubation and of non-specific staining in control preparations using normal rabbit serum in lieu of specific rabbit antiserum to ALLA or Ia excluded selective cell death and increased non-specific stain as causes of the observed increase in fluorescent cell staining. The enhanced antigen expression was observed in those samples in which antigens were detectable on only a small fraction of the leukemic cells. The results demonstrate the necessity of re-examination of leukemic cells for the presence of ALLA and Ia following overnight incubation especially in antigen negative cases.

Varicella in immunocompromised children. Incidence of abdominal pain and organ involvement.

The medical records of 31 immunocompromised patients who experienced varicella infections from 1975 to 1982 were reviewed. Fifteen of these patients had visceral involvement. In these 15 patients, two clinical patterns of progression were noted: (1) Eleven patients with life-threatening involvement experienced hepatitis (n = 11), pneumonitis (n = 11), abdominal pain (n = 11), encephalopathy (n = 10), coagulopathy (n = 10), inappropriate antidiuretic hormone (ADH) syndrome (n = 10), back pain or myalgia (n = 5), and myocarditis (n = 1). Seven of these patients survived, all without sequelae. (2) Four patients with a milder course experienced subclinical hepatitis (n = 4), mild pneumonitis (n = 4), postinfectious encephalitis (n = 1), and septic arthritis associated with disseminated intravascular coagulopathy (n = 1). All four of these patients recovered completely. In patients with severe involvement, intense abdominal pain was frequently the first sign of dissemination. Abdominal pain and inappropriate ADH syndrome were unexplained and have not been previously described in progressive varicella. A predictable pattern of organ involvement enabled starting therapy early and resulted in the survival of 11 of 15 patients.