Prolonging the duration of post-infusion scalp cooling in the prevention of anthracycline-induced alopecia: a randomised trial in patients with breast cancer treated with adjuvant chemotherapy.

PURPOSE: Scalp cooling as a method to reduce the incidence of chemotherapy-induced alopecia (CIA) is increasingly used in daily practice worldwide. However, in patients treated with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), scalp cooling fails in 48-67% of patients. This study investigated the efficacy of extended duration of post-infusion scalp cooling in breast cancer patients treated with this regimen. METHODS: In this prospective multi-centre randomised study, 102 patients with early breast cancer treated with adjuvant FEC chemotherapy were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 90 or 150 min. The primary endpoint was the need to wear a wig or other head covering to mask visible hair loss. RESULTS: Sixteen out of 48 patients (33%) treated with 90 min of post-infusion cooling did not need any head covering, compared with 21 out of 46 patients (45%) treated with 150 min of post-infusion cooling (p = 0.2). WHO grades 2-3 (moderate-complete) alopecia were reported more often in patients treated with 90-min post-infusion cooling time (n = 25/51 (49%) versus n = 17/51 (33%); p = 0,02). Scalp cooling was well-tolerated (mean Visual Analogue Score 7.4) and only three patients (3%) stopped due to intolerance during treatment. CONCLUSIONS: Extending the duration of 90-min post-infusion scalp cooling to 150 min in patients treated with adjuvant FEC chemotherapy was well-tolerated but did not significantly diminish the need for head covering. However, grades 2-3 alopecia was seen less often with prolonged post-infusion scalp cooling.

[5-HT3-antagonists as a substitute for metoclopramide and domperidone: a literature review]. / 5-HT3-receptorantagonisten als vervangers van metoclopramide en domperidon.

OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron. These had to be randomised controlled clinical studies into the known indications for metoclopramide and domperidone for prevention and treatment of nausea and vomiting. Two reviewers independently selected articles based on the title and abstract, then assessed for eligibility based on the full texts. RESULTS: In total, 56 articles were included in this review. The conclusion in 51 studies was that the efficacy of 5-HT3-antagonists in nausea and vomiting is comparable or even superior to that of metoclopramide. Metoclopramide more often caused extrapyramidal side effects; 5-HT3-antagonists were more likely to cause headaches and constipation. The majority of the studies compared metoclopramide with ondansetron. None of the articles studied palonosetron, and only one study compared domperidone with a 5-HT3-antagonist. CONCLUSION: We found enough evidence to presume that metoclopramide can be replaced by 5-HT3-antagonists for preventing delayed chemotherapy-induced nausea and vomiting and for prophylaxis or treatment of postoperative nausea and vomiting. More research is needed into the other indications and into the substitutability of domperidone.

Preventability of trauma deaths in a Dutch Level-1 trauma centre.

BACKGROUND: Monitoring the quality of trauma care is frequently done by analysing the preventability of trauma deaths and errors during trauma care. In the Academic Medical Center trauma deaths are discussed during a monthly Morbidity and Mortality meeting. In this study an external multidisciplinary panel assessed the trauma deaths and errors in management of a Dutch Level-1 trauma centre for (potential) preventability. METHODS: All patients who died during or after presentation in the trauma resuscitation room in a 2-year period were eligible for review. All information on trauma evaluation and management was summarised by an independent research fellow. An external multidisciplinary panel individually evaluated the cases for preventability of death. Potential errors or mismanagements during the admission were classified for type, phase and domain. Overall agreement on (potential) preventability was compared between the external panel and the internal M&M consensus. RESULTS: Of the 62 evaluated trauma deaths one was judged as preventable and 17 were judged as potentially preventable by the review panel. Overall agreement on preventability between the review panel and the internal consensus was moderate (Kappa 0.51). The external panel judged one death as preventable compared with three from the internal consensus. The interobserver agreement between the external panel members was also moderate (Kappa 0.43). The panel judged 31 errors to have occurred in the (potential) preventable death group and 23 errors in the non-preventable death group. Such errors included choice or sequence of diagnostics, rewarming of hypothermic patients, and correction of coagulopathies. CONCLUSIONS: The preventable death rate in the present study was comparable to data in the available literature. Compared to internal review, the external, multidisciplinary review did not find a higher preventable death rate, although it provided several insights to optimise trauma care.

Factors influencing catheter-related infections in the Dutch multicenter study on high-dose chemotherapy followed by peripheral SCT in high-risk breast cancer patients.

Neutropenia following high-dose chemotherapy leads to a high incidence of infectious complications, of which central venous catheter-related infections predominate. Catheter-related infections and associated risk factors in 392 patients participating in a randomized adjuvant breast cancer trial and assigned to receive high-dose chemotherapy and peripheral stem-cell reinfusion were evaluated. Median catheter dwell time was 25 days (range 1-141). Catheter-related infections were seen in 28.3% of patients (11 infections per 1000 catheter-days). Coagulase-negative staphylococci were found in 104 of 186 positive blood cultures (56%). No systemic fungal infections occurred. Cox regression analysis showed that duration of neutropenia >10 days (P=0.04), using the catheter for both stem-cell apheresis and high-dose chemotherapy (P= <0.01), and use of total parenteral nutrition (TPN, P=0.04) were predictive for catheter-related infections. In conclusion, a high incidence of catheter-related infections after high-dose chemotherapy was seen related to duration of neutropenia, use of the catheter for both stem-cell apheresis and high-dose chemotherapy, and use of TPN. Selective use and choice of catheters could lead to a substantial reduction of catheter-related infectious complications.

A patient treated with olanzapine developing diabetes de novo: proposal for hyperglycaemia screening.

We report a patient with schizophrenia who developed diabetes mellitus during treatment with olanzapine. The case confirms the pattern of atypical antipsychotic-related diabetic emergencies: rapid onset in relatively young patients, often with severe glucose derangements and serious complications. As diabetic emergencies have a high morbidity and mortality, regular glucose screening should be performed in patients with schizophrenia treated with atypical antipsychotics.

Sarcoidosis mimicking metastatic disease: a case report and review of the literature.

Osseous and in particular vertebral sarcoidosis is exceedingly rare and a difficult diagnosis to establish because it may simulate many diseases, including even metastatic malignancy. we present a patient with lesions in bones, lungs and lymph nodes, mimicking the presence of extensive metastatic disease. our case emphasises the importance of histological evidence before the diagnosis of osseous sarcoidosis can be made with confidence.

Relevance of high-dose chemotherapy in solid tumours.

Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.

Factors influencing haematological recovery following high-dose chemotherapy and peripheral stem-cell transplantation for haematological malignancies; 1-year analysis.

Peripheral blood counts and factors influencing haematological recovery in 98 patients with a relapse-free survival of > or =1 year treated with high-dose chemotherapy (HDC) and peripheral stem-cell transplantation (PSCT) for haematological malignancies were analysed. One year after PSCT full haematological recovery was demonstrated for haemoglobin (Hb) in 47% of patients, for the white blood cell count (WBC) in 94%, and for platelets in 64%; 39% had a trilineage recovery. In the multivariate analysis, recovery was influenced by age (P=0.002), number of reinfused CD34+ cells (P=0.016), Hb at start of HDC (P=0.001), and platelets at start of HDC (P=0.008). One year following PSCT, 61% of patients still have subnormal values in one or more haematopoietic cell lineage, suggesting a limited bone-marrow reserve. Long-term recovery is highly dependent on age, blood counts at start of HDC and number of reinfused CD34+ cells without a threshold, all reflecting the residual function of bone marrow before HDC. Reinfusing more CD34+ cells can accelerate long-term haematological recovery.

Chemotherapy for metastatic seminoma in elderly patients.

Testicular germ cell tumours are rarely diagnosed in the elderly. In view of the high cure rate of these tumours, even in elderly patients treatment with chemotherapy and/or radiotherapy should be considered. In this report we describe two older patients with metastatic testicular seminoma. Both were treated with chemotherapy with curative intention. Described are the problems related to treatment with chemotherapy in these elderly.

Screening for infectious foci in breast cancer patients prior to high-dose chemotherapy and stem cell transplantation.

UNLABELLED: Cancer patients treated with high-dose chemotherapy (HDC) followed by peripheral stem cell transplantation are at risk for infections during neutropenia. Our standard policy was to screen for potential infectious foci prior to HDC. Screening for infectious foci consisted of chest and sinus roentgenograms and a visit to the ear-nose-throat surgeon (ENT surgeon) and the dentist. The purpose of this study was to evaluate this approach. Between 1993 and 2000, 73 breast cancer patients received HDC. RESULTS: All chest roentgenograms were normal. ENT screening yielded in three (symptomatic) patients a potential infectious focus. In 32 patients (44%) a potential dental infectious focus was diagnosed and treated. During neutropenia after HDC clinical infections occurred in 15 patients (21%). In only 5 patients (7%) the infection focus was probably the upper respiratory tract. CONCLUSION: Potential ENT infectious foci were infrequent and all were symptomatic. Potential dental infectious foci were seen quite often; whether they would have had clinical impact if left untreated remains speculative.

How to diagnose cardiac tamponade.

Malignant pericardial effusion is a potentially fatal complication of malignancy unless recognised and treated promptly. Patients with this condition are often difficult to diagnose. Physical examination, chest radiography and electrocardiography have poor diagnostic values in identification of patients with pericardial effusion. Echocardiography, which allows rapid confirmation of the presence of an effusion and precise assessment of its haemodynamic impact, is the gold standard for diagnosis.

Dacarbazine DTIC and carboplatin as an outpatient treatment for disseminated malignant melanoma.

Occasionally long-term survival in disseminated melanoma can be obtained through chemotherapy. We treated 22 patients with disseminated melanoma with an outpatient regimen consisting of dacarbazine (DTIC) and carboplatin. Three patients had a complete response lasting 4+, 9 and 9 months (survival 4+, 10 and 16 months), respectively; 3 patients had a partial response lasting 4, 6 and 8 months (survival 6+, 11+ and 14 months), respectively. Overall response was 27% (95% confidence interval 11-50%). Toxicity was relatively mild and mainly due to nausea. In 3 patients the dose of carboplatin was reduced because of grade 4 haematological toxicity. This described easy outpatient regimen shows comparable results as other polychemotherapeutic regimens in disseminated melanoma, but with a relatively mild toxicity profile.

Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours.

long-term peripheral blood counts and factors influencing long-term trilineage haematological recovery of consecutive patients in a single institution treated with high-dose chemotherapy (hdc) and abmt or psct for solid tumours were examined. patients with a relapse-free survival of >1 year were included in the analysis (n = 131). Peripheral blood counts were examined 6 months and yearly following transplantation. Median follow-up was 4.1 years (range 1-10+ years). Three years after transplantation 91% of patients had normal white blood counts (WBC), 94% normal haemoglobin (Hb) and 75% normal platelets. Trilineage recovery was complete in 70% (n = 83) at 3 years and 85% (n = 50) at 5 years. Recovery of Hb occurred before WBC and platelet recovery. Approximately 25% of patients displayed an elevated MCV throughout the follow-up period. These long-term results were independent of age, high-dose regimen, number of reinfused stem cells and stem cell source. Double (n = 12) vs single (n = 119) transplantations showed significantly slower trilineage recovery and higher MCV. No secondary graft failure, myelodysplasia or leukaemia was encountered. In conclusion, complete trilineage recovery after HDC followed by ABMT or PSCT occurs slowly. PSCT and ABMT are capable of maintaining long-term haematopoiesis. Slower recovery is seen after double transplantations. The results suggest lasting implications for bone marrow function after autologous transplantation.

Delirium after interleukin-2 and alpha-interferon therapy for renal cell carcinoma.

A 55-year-old man receiving alpha-interferon and interleukin-2 therapy for renal cell carcinoma presented with seizures and delirium. A CT-scan of the cerebrum did not reveal any disorder. Both alpha-interferon and interleukin-2 were stopped. Treatment with steroids led to complete regression of central nervous system symptomatology. We emphasize the importance of ruling out iatrogenesis in patients treated with alpha-interferon and/or interleukin-2 who display neuropsychiatric symptoms.

Central diabetes insipidus preceding acute myeloid leukemia with t(3;12)(q26;p12).

A 52-year-old woman presented with polyuria and polydipsia. A diagnosis of central diabetes insipidus (DI) was made, which turned out to be the first sign of acute myeloid leukemia (AML). Cytogenetic analysis revealed a balanced translocation between chromosome 3 and 12 t(3;12)(q26;p12). The patient was treated with standard induction chemotherapy and vasopressin. Before consolidation chemotherapy could be administered, deep venous thrombosis was diagnosed and leukemia relapsed. Rescue chemotherapy was started. This is the first report of an association between AML with t(3;12) and DI. Its possible pathogenesis is discussed with a review of the literature.

Catecholamine dependency in a polytrauma patient: relative adrenal insufficiency?

A 65-year-old polytrauma patient was admitted post-operatively to the intensive care unit. His situation deteriorated with hemodynamic instability and continuous high fever. An infectious focus could not be found and repeated cultures remained negative. Empirical administration of antibiotics and changing of lines did not have any effect on the clinical picture. It was impossible to lower the dose of catecholamines because of repeated occurrence of hypotension, despite optimal hydration state and filling pressures. On the 15th day of admission intravenous hydrocortisone was started on suspicion of relative adrenal insufficiency. This action resulted in rapid hemodynamic recovery, disappearance of fever and enabled rapid tapering of the dose of noradrenaline. Incidence of relative adrenal insufficiency and diagnostic strategies are discussed in the population of critically intensive care patients.

An unusual presentation of sepsis caused by coagulase-negative staphylococci.

We describe a 25-year-old male presenting with fever during the non-neutropenic phase of chemotherapy. The presentation was that of a viral infection. The cause of the fever turned out to be a bacteremia with coagulase-negative staphylococci (CONS) originating from a totally implanted venous access port (VAP). We briefly discuss the different types of VAP-related infections and treatment modalities.