Management of dermatofibrosarcoma protuberans with fibrosarcomatous transformation: an evidence-based review of the literature.

Fibrosarcomatous transformation represents a rare event in dermatofibrosarcoma protuberans (DFSP) with unpredictable biological behaviour. No guidelines for the adequate treatment of patients with this rare neoplasm have been published. Herein, we present a comprehensive review of the literature comprising 157 patients with transformed DFSP focussing on surgical and adjuvant treatment modalities for this tumour. In the cohort examined, local recurrence occurred in 36% of cases and was significantly lower in patients treated by wide excision with margins ≥2 cm when compared with those treated with local excision without defined margins (P = 0.01). Consistently, negative margin status was associated with a lower recurrence rate when compared with positive or unknown margin status (P = 0.01). Distant metastases were detected in 13% of patients, which is significantly higher when compared with ordinary dermatofibrosarcoma protuberans. Systemic dissemination was preceded by local recurrence in 81% of cases, and is therefore strongly associated with tumour recurrence (P ≤ 0.001). The present data confirm that wide excision with margins ≥ 2 cm represent the gold standard in the treatment of transformed dermatofibrosarcoma protuberans, and prevents recurrence as well as metastasis. When R0-resection is not feasible, adjuvant radiation should be considered for cases with incomplete resection or unknown surgical margins. Irresectable or metastatic transformed DFSP harbouring the COL1A1-PDGFB fusion gene should be treated with imatinib in the palliative setting or as an adjunctive treatment before surgery, although responses may be short-lasting.

Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma.

Cell adhesion molecule 1 (CADM1) is a putative tumour suppressor gene, which is downregulated in many solid tumours. In neuroblastoma, loss of CADM1 expression has recently been found in disseminated tumours with adverse outcome, prompting us to investigate its role in neuroblastoma tumour progression. Oligonucleotide-microarray analysis of 251 neuroblastoma specimens demonstrated that CADM1 downregulation is associated with unfavourable prognostic markers like disseminated stage 4, age >18 months, MYCN amplification and chromosome 11q alterations (P<0.001 each). Furthermore, low CADM1 expression was significantly correlated with unfavourable gene expression-based classification (P<0.001) and adverse patient outcome (P<0.001). Bisulphite sequencing and genetic analysis of 18 primary neuroblastomas suggested that neither haploinsufficiency nor hypermethylation is regularly involved in CADM1 gene silencing in neuroblastoma, which is in contrast to results obtained in other malignancies. In addition, no mutations disrupting the CADM1 reading frame were found in 25 primary neuroblastomas. Over-expression of CADM1 in neuroblastoma cells resulted in significant reduction of proliferation, viability and colony formation in soft agar. Collectively, our results suggest that downregulation of CADM1 tumour suppressor gene expression is a critical event in neuroblastoma pathogenesis resulting in tumour progression and unfavourable patient outcome.

Civilian health during WWI and the causes of German defeat: a reexamination of the winter hypothesis.

This paper is a reexamination of the Winter hypothesis, which holds that there was a marked difference in the development of civilian health during the First World War between the central powers and the Western allies. Ultimate success on the battlefield, according to Winter, required balancing the needs of the military with civilian demands; Germany lost because it failed to achieve such a balance. The resulting decline in health standards undermined the war effort and eventually led to defeat. This article proceeds in two steps. First, it demonstrates that Winter's data does not allow him to make a proper comparison between the two camps. Second, I argue that his hypothesis can be refuted once a truly comparable source is used--infant mortality rated. There is as yet no convincing evidence to suggest that the outcome of the First world War was determined by public health policy.

Responsible prescribing of controlled substances.

One-third of the disciplinary actions against physicians in 1990 involved prescriptions for controlled or abusable drugs. Problems involving the prescribing of controlled medications may occur because of overdose, dependence or use by known drug abusers. A common problem facing the physician is the identification of potential overdose victims and addicted patients. Requests for early prescription refills, claims of lost prescriptions, frequent after-hours calls and patient intolerance to nonnarcotic pain-relieving drugs should raise suspicions of drug abuse.

Metaphor as a diagnostic tool.

A case study is reported wherein the patient's frequent use of metaphors was used as presumptive evidence that the patient had been misdiagnosed ten years earlier as having central nervous system disease. The ability to produce metaphors depends upon the capacity to condense several meanings into a word or two, and this in turn implies a rather active associative process. Concretism, not associative richness, characterizes central nervous system disease. The presumption as regards diagnosis was supported by subsequent data including the patient's response to psychotherapy.

Dream analysis in the treatment of an eleven-year-old boy.

The treatment of an eleven-year-old boy with severe enuresis, facial tic, marked social maladjustment, passivity, and effeminacy was guided by the following principles: (1) Personality development was set in motion by encouraging age- and gender-appropriate behavior, by providing and identification model, and by upholding values which reflect normal male behavior. (2) Unconscious pathogenic forces were mobilized, analyzed, and resolved. (3) Environmental factors which facilitated growth were added and those which inhibited growth were removed. (4) The doctor took a clear stand for health and against sickness. (5) Responsibility for the conduct, progress and outcome of treatment rested with the doctor. The treatment was therefore guided by a synthesis of three conceptual models: developmental, analytic, and medical. The patient was seen for one hundred hours over a two-and-one-half-year period. Dream analysis provided the primary means by which unconscious conflicts were brought into consciousness.