Richard P. Kaplan

Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study.

BACKGROUND Men with high serum prostate specific antigen usually undergo transrectal ultrasound-guided prostate biopsy (TRUS-biopsy). TRUS-biopsy can cause side-effects including bleeding, pain, and infection. Multi-parametric magnetic resonance imaging (MP-MRI) used as a triage test might allow men to avoid unnecessary TRUS-biopsy and improve diagnostic accuracy. METHODS We did this multicentre, paired-cohort, confirmatory study to test diagnostic accuracy of MP-MRI and TRUS-biopsy against a reference test (template prostate mapping biopsy [TPM-biopsy]). Men with prostate-specific antigen concentrations up to 15 ng/mL, with no previous biopsy, underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. The conduct and reporting of each test was done blind to other test results. Clinically significant cancer was defined as Gleason score ≥4 + 3 or a maximum cancer core length 6 mm or longer. This study is registered on ClinicalTrials.gov, NCT01292291. FINDINGS Between May 17, 2012, and November 9, 2015, we enrolled 740 men, 576 of whom underwent 1·5 Tesla MP-MRI followed by both TRUS-biopsy and TPM-biopsy. On TPM-biopsy, 408 (71%) of 576 men had cancer with 230 (40%) of 576 patients clinically significant. For clinically significant cancer, MP-MRI was more sensitive (93%, 95% CI 88-96%) than TRUS-biopsy (48%, 42-55%; p<0·0001) and less specific (41%, 36-46% for MP-MRI vs 96%, 94-98% for TRUS-biopsy; p<0·0001). 44 (5·9%) of 740 patients reported serious adverse events, including 8 cases of sepsis. INTERPRETATION Using MP-MRI to triage men might allow 27% of patients avoid a primary biopsy and diagnosis of 5% fewer clinically insignificant cancers. If subsequent TRUS-biopsies were directed by MP-MRI findings, up to 18% more cases of clinically significant cancer might be detected compared with the standard pathway of TRUS-biopsy for all. MP-MRI, used as a triage test before first prostate biopsy, could reduce unnecessary biopsies by a quarter. MP-MRI can also reduce over-diagnosis of clinically insignificant prostate cancer and improve detection of clinically significant cancer. FUNDING PROMIS is funded by the UK Government Department of Health, National Institute of Health Research-Health Technology Assessment Programme, (Project number 09/22/67). This project is also supported and partly funded by UCLH/UCL Biomedical Research Centre and The Royal Marsden and Institute for Cancer Research Biomedical Research Centre and is coordinated by the Medical Research Council Clinical Trials Unit (MRC CTU) at UCL. It is sponsored by University College London (UCL).

Bullous pyoderma gangrenosum after granulocyte colony-stimulating factor treatment

The hematopoietic growth factors are under investigation for the treatment of patients with chemotherapy‐induced bone marrow suppression. One such trial at the University of California, Los Angeles involves chemotherapy with or without granulocyte colony‐stimulating factor (G‐CSF) in patients with small cell lung cancer. The authors report a case of a patient who had bullous pyoderma gangrenosum at the site of previous eczema during treatment with G‐CSF. The lesions resolved promptly when the drug was discontinued. Other investigators have recently reported inflammatory complications of G‐CSF and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) but this is the first case report of biopsy‐proven neutrophilic dermatosis associated with administration of a hematopoietic growth factor. Patients should be monitored for development of inflammatory processes during G‐CSF therapy and this therapy should be given with caution to those patients with existing inflammatory conditions.

Unusual manifestations of secondary syphilis and abnormal humoral immune response to Treponema pallidum antigens in a homosexual man with asymptomatic human immunodeficiency virus infection

The case presented here involves a 32-year-old homosexual man with human immunodeficiency virus (HIV) seropositivity and unusual manifestations of secondary syphilis. The patient presented with syphilitic keratoderma and chorioretinitis, and his appearance superficially resembled that of a patient with Reiters syndrome. Although nontreponemal and treponemal tests for syphilis showed reactivity, the patients humoral immune response to individual polypeptides of Treponema pallidum, measured by Western blot analysis, was markedly abnormal. The possible relationship between asymptomatic HIV infection and an abnormal humoral immune response to a second pathogen, in this case T. pallidum, is discussed. Our case is one of several recent cases of active syphilis reported in individuals with HIV seropositivity.

Maffucci's syndrome: Two case reports with a literature review

Sixty-three cases of Maffuccis syndrome in the English literature plus two additional cases of our own are reviewed. This syndrome is nonhereditary and is characterized by multiple enchondromas and hemangiomas. It occurs in all races with no sex predominance. The enchondromas and hemangiomas can occur anywhere but are most common in the hands. Long bone involvement is common and leads to progressive skeletal deformity and pathologic fractures. The incidence of malignancies in patients with this syndrome is high. Chondrosarcomas are especially common and occur in 30% of the patients.

Etretinate therapy for psoriasis: Clinical responses, remission times, epidermal DNA and polyamine responses

A prospective study was carried out over 12 months involving twenty patients with psoriasis vulgaris who were treated with all-trans-aromatic derivative of vitamin A, etretinate. Etretinate was found to be an effective therapy for this skin disorder. Arthritis accompanying psoriasis vulgaris in four of seven of our patients was greatly improved by retinoid therapy. Side effects were found to be dose-related and included mucocutaneous abnormalities as well as abnormalities of blood lipids and liver function tests. Maintenance therapy appears to be required in nearly all patients, with relapse occurring within approximately 8 weeks. Polyamine biosynthesis has been determined previously to be accelerated in patients with psoriasis vulgaris. Polyamines (putrescine [Pu], spermidine [Sp], and spermine [Sm] were measured in skin samples of six patients with stable plaque-stage psoriasis before treatment and at 4 weeks during treatment. Pu, Sp, Sm levels, as well as the Sp/Sm ratio, fell. Epidermal DNA synthesis is increased in involved and noninvolved psoriatic skin; it was measured before and during treatment (at 4 weeks) in this study and found not to fall significantly during this period of time. Polyamine levels therefore decreased prior to any significant expected decrease in epidermal DNA synthesis measured in both involved and uninvolved skin.

Esophagitis dissecans superficialis associated with pemphigus vulgaris

A number of dermatologic conditions may have associated esophageal manifestations. Teleologically, this may be because both the skin and the esophagus are lined by stratified squamous epithelium. Bullous dermatoses that may produce blisters, erosions, and/or stricture of the esophagus include cicatricial pemphigoid, Hailey-Hailey disease, Dariers disease, various forms of epidermolysis bullosa, bullous pemphigoid, and pemphigus vulgaris. Very rarely, bullous diseases may affect the esophagus in such a manner that there is a sloughing of the entire mucous membrane. The production of such an esophageal cast has been termed esophagitis dissecans superficialis. This is the second case recorded in the medical literature of pemphigus vulgaris associated with esophagitis dissecans superficialis. Additionally, this is the first case of pemphigus vulgaris in which the esophagus is demonstrated to be positive by direct immunofluorescence.

Drug-induced pemphigus related to angiotensin-converting enzyme inhibitors.

We report a case of drug-induced pemphigus caused by an angiotensin-converting enzyme inhibitor, captopril. The cutaneous reaction remitted after withdrawal of captopril therapy. Unique to this case, however, was the substitution of another angiotensin-converting enzyme inhibitor, enalapril, without exacerbation of the pemphigus. To the best of our knowledge, this is the first reported patient with captopril-induced pemphigus in whom no new lesions developed after subsequent treatment with enalapril. A difference in chemical structure between these two drugs, particularly of a sulfur moiety, may help explain why the drug-induced disease did not recur.

Congenital smooth-muscle hamartoma.

ABSTRACT: Congenital smooth‐muscle hamartomas are rare, benign tumors of the skin, since their original description in 1969, 16 case reports have appeared in the literature, with 7 cases reported within the last year. We describe the 17th patient with this lesion and have included a review of the literature. In addition, we describe three morphologic types of smooth muscle cells–the pale cells, dark cells, and intermediate cells–found on electron microscopy, and the features that support our belief that these may reflect different stages of maturity of the smooth‐muscle cells. In addition to the smooth muscle, bundles of nerve fibers (both unmyelinated and myelinated) appear to be an intrinsic part of the lesion, as are the prominent vellus hairs. Congenital smooth muscle hamartoma thus appears to be an organoid nevus.

Strengthening clinical cancer research in the United Kingdom.

Background:In 1999, 270 000 cases of cancer were registered in the United Kingdom, placing a large burden on the NHS. Cancer outcome data in 1999 suggested that UK survival rates were poorer than most other European countries. In the same year, a Department of Health review noted that clinical trials accrual was poor (<3.5% of incident cases) and hypothesised that increasing research activity might improve outcomes and reduce the variability of outcomes across England. Thus, the National Cancer Research Network (NCRN) was established to increase participation in cancer clinical research.Methods:The NCRN was established in 2001 to provide a robust infrastructure for cancer clinical research and improvements in patient care. Remit of NCRN is to coordinate, support and deliver cancer clinical research through the provision of research support staff across England. The NCRN works closely with similar networks in Scotland, Wales and the Northern Ireland. A key aim of NCRN is to improve the speed of research and this was also assessed by comparing the speed of study delivery of a subset of cancer studies opening before and after NCRN was established.Results:Patient recruitment increased through NCRN, with almost 32 000 (12% of annual incident cases) cancer patients being recruited each year. Study delivery has improved, with more studies meeting the recruitment target – 74% compared with 39% before NCRN was established.Conclusion:The coordinated approach to cancer clinical research has demonstrated increased accrual, wide participation and successful trial delivery, which should lead to improved outcomes and care.

Measuring the incremental cost of clinical cancer research.

PURPOSE To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.