Photodynamic therapy with systemic meta-tetrahydroxyphenylchlorin in the treatment of anal intraepithelial neoplasia, grade 3.

BACKGROUND AND OBJECTIVE: Anal cancer and preneoplastic anal lesions (anal intraepithelial neoplasia, AIN) rising especially in men having sex with men (MSM). There are no widely accepted treatment standards for AIN. Photodynamic therapy (PDT) using the systemic sensitizer meta-tetrahydroxyphenylchlorin (mTHPC) has the potential to treat the anal area even when the exact borders of the preneoplastic anal lesion cannot easily be visualized. STUDY DESIGN/MATERIALS AND METHODS: In this prospective intervention study, 15 HIV-positive MSM with AIN 3 were treated in 25 PDT-sessions using mTHPC intravenously administered at drug doses of 0.075-0.15 mg ml(-1) and illumination at 48 hours. The illumination was performed using a custom made applicator using either red light (652 nm) to a measured intended fluence of 10 and 20 J cm(-2) and green light (532 nm) to a measured intended fluence of 105, 210, and 340 J cm(-2) . Red and green illuminations were performed at a (green) equivalent fluence rate of 105 mW cm(-2) . RESULTS: Initial complete response was seen in 7/25 (28%) of treatments and another 4/25 (16%) initial partial responses. After an average 8 months, recurrences were detected in 7/11 (64%) of sessions that initially showed response. A total 4/25 (16%) showed persistent complete response 6-15 months after green light illumination. Red light illuminations caused more significant side effects combined with no persistent complete response. Reported side effects were intense pain, bloody and purulent rectal discharge, and anal stricture formation, in one patient. CONCLUSION: The results show that the use of systemic mTHPC is partially effective for the treatment of AIN 3.

COL4A2 mutation associated with familial porencephaly and small-vessel disease.

Familial porencephaly, leukoencephalopathy and small-vessel disease belong to the spectrum of disorders ascribed to dominant mutations in the gene encoding for type IV collagen alpha-1 (COL4A1). Mice harbouring mutations in either Col4a1 or Col4a2 suffer from porencephaly, hydrocephalus, cerebral and ocular bleeding and developmental defects. We observed porencephaly and white matter lesions in members from two families that lack COL4A1 mutations. We hypothesized that COL4A2 mutations confer genetic predisposition to porencephaly, therefore we sequenced COL4A2 in the family members and characterized clinical, neuroradiological and biochemical phenotypes. Genomic sequencing of COL4A2 identified the heterozygous missense G1389R in exon 44 in one family and the c.3206delC change in exon 34 leading to frame shift and premature stop, in the second family. Fragmentation and duplication of epidermal basement membranes were observed by electron microscopy in a c.3206delC patient skin biopsy, consistent with abnormal collagen IV network. Collagen chain accumulation and endoplasmic reticulum (ER) stress have been proposed as cellular mechanism in COL4A1 mutations. In COL4A2 (3206delC) fibroblasts we detected increased rates of apoptosis and no signs of ER stress. Mutation phenotypes varied, including porencephaly, white matter lesions, cerebellar and optic nerve hypoplasia and unruptured carotid aneurysm. In the second family however, we found evidence for additional factors contributing to the phenotype. We conclude that dominant COL4A2 mutations are a novel major risk factor for familial cerebrovascular disease, including porencephaly and small-vessel disease with reduced penetrance and variable phenotype, which might also be modified by other contributing factors.

Rhabdoid tumor mimicking hemangioma.

We report a young boy with a malignant tumor, which remained unrecognized for 8 months because it was assumed to be a hemangioma. The presentation of a rhabdoid tumor mimicking hemangioma is very rare. It was reported only on two earlier occasions. Rhabdoid tumors are one of the most aggressive types of malignancies encountered in pediatric oncology. It is important to recognize that a fast growing vascular lesion in a child will often be a hemangioma, but could also be an aggressive tumor.

Imatinib mesylate for children with dermatofibrosarcoma protuberans (DFSP).

Dermatofibrosarcoma protuberans (DFSP) is a rare malignant soft tissue tumor in children. DFSP is characterized by a specific fusion of the platelet-derived growth factor beta (PDGFbeta) with the collagen type 1alpha1 (COL1alpha1) gene which renders these tumors responsive to targeted therapy with tyrosine kinase inhibitors, such as imatinib mesylate, as is reported in adults. In the current report, we describe the first small pediatric DFSP series, in which response to imatinib mesylate contributed to successful treatment outcome.

Clinical aspects of diffuse cutaneous mastocytosis in children: two variants.

OBJECTIVE: This paper describes two different clinical presentations of diffuse cutaneous mastocytosis (DCM), based on the largest series published to date. As far as we are aware, these two variants of clinical presentations have not yet been reported. DESIGN: We undertook a case controlled analysis of 8 children with DCM. Results of laboratory testing including mast cell mediator levels, and clinical symptoms on presentation and during follow-up were analyzed. RESULTS: The levels of relevant mast cell mediators were initially high in all cases but declined sharply later on. There was a reduction of 20% in 2 of the 7 cases, whereas there was a reduction of 80% in the remaining 5. No reduction occurred in 1 case. Clinical improvement followed the same pattern. CONCLUSIONS: DCM is a rare variant of cutaneous childhood onset mastocytosis. Various forms show the same or overlapping features at various times. It appears to follow a course similar to that in other types of childhood onset mastocytosis, taking into account the decreased symptoms and the levels of mast cell mediators during follow-up. Obtaining a bone marrow biopsy should be considered only in those cases where there is no improvement or even worsening of signs or symptoms and persistent elevated levels of mast cell mediators.

Hamartomas of the oro- and nasopharyngeal cavity in infancy: two cases and a short review.

INTRODUCTION: Oro- and nasopharyngeal masses are rare in infancy and consist of developmental anomalies and, mostly benign, neoplasms. CASE REPORT: We report two infants with a tumour in the ear-nose-throat region. DISCUSSION: As shown by our cases, the clinical presentation of an oropharyngeal mass in infancy varies from respiratory insufficiency at birth to incidental finding by the parents a few months after birth.

Mastocytosis in children: a protocol for management.

Mastocytosis is characterized by an increased number of mast cells with an abnormal growth and accumulation in one or more organs. In most children mastocytosis is limited to the skin (cutaneous mastocytosis) and often transient as compared with that in adults in whom mastocytosis is usually progressive and systemic. Generally, we recognize three more common forms of cutaneous mastocytosis: maculopapulous mastocytosis (formerly urticaria pigmentosa), mastocytoma of skin, and diffuse cutaneous mastocytosis. Childhood mastocytosis can further be divided into cutaneous mastocytosis (nonpersisting and persisting) and systemic mastocytosis (extremely rare). An approach to management using a set protocol is described in table form. In most cases of mastocytosis, only yearly checkups are necessary and no treatment is required; preventive recommendations are warranted in those individuals with systemic disease and constitutional symptoms. Symptomatic therapy is advised in only a minority of cases. This article is meant as a guideline for physicians involved in the care of children with mastocytosis and their parents.

Discriminating basal cell carcinoma from perilesional skin using high wave-number Raman spectroscopy.

An expanding body of literature suggests Raman spectroscopy is a promising tool for skin cancer diagnosis and in-vivo tumor border demarcation. The development of an in-vivo diagnostic tool is, however, hampered by the fact that construction of fiber optic probes suitable for Raman spectroscopy in the so-called fingerprint region is complicated. In contrast, the use of the high wave-number region allows for fiber optic probes with a very simple design. We investigate whether high wave-number Raman spectroscopy (2800 to 3125 cm(-1)) is able to provide sufficient information for noninvasive discrimination between basal cell carcinoma (BCC) and noninvolved skin. Using a simple fiber optic probe, Raman spectra are obtained from 19 BCC biopsy specimens and 9 biopsy specimens of perilesional skin. A linear discriminant analysis (LDA)-based tissue classification model is developed, which discriminates between BCC and noninvolved skin with high accuracy. This is a crucial step in the development of clinical dermatological applications based on fiber optic Raman spectroscopy.

Efficacy of 25% diluted fluticasone propionate 0.05% cream as wet-wrap treatment in cutaneous mastocytosis.

BACKGROUND: Mastocytosis is a disorder that can be subdivided into two forms: cutaneous and systemic. Patients with cutaneous mastocytosis only may suffer from cosmetic problems. Topical steroid application has been shown to be effective in cases of limited skin lesions. METHODS: A case-controlled pilot study was conducted during a 6-weeks treatment using diluted 25% fluticasone propionate 0.05% cream under wet-wrap occlusion in 5 adults and 6 children. Improvement was measured up to the 24th week after treatment using the SCORMA Index. RESULTS: The results of this pilot study showed a partial but clear cosmetic improvement in 9 of the 11 patients. The mean SCORMA Index decreased after treatment from 38 to 26. CONCLUSION: 25% dilution of fluticasone propionate 0.05% cream under wet-wrap occlusion is an alternative treatment modality for alleviating the symptoms of cutaneous mastocytosis, but the improvement may be moderate and fall short of the patient's expectations.

Pediatric aggressive fibromatosis: a retrospective analysis of 13 patients and review of literature.

BACKGROUND: Aggressive fibromatosis (AF) is a soft tissue tumor and is rare in childhood, with high potential for local invasiveness and recurrence. General recommendations for the clinical management of pediatric patients with AF remain undetermined. METHODS: The authors retrospectively analyzed 13 children with AF who were diagnosed from 1987 until 2004 in the Erasmus MC-Sophia Children's Hospital, and a review of the pediatric literature was conducted. RESULTS: Two patients received preoperative chemotherapy with combined vincristine, actinomycin-D, and cyclophosphamide (VAC). All 13 patients underwent surgery. Three of six patients who underwent incomplete resection received adjuvant treatment, two patients received radiotherapy, and one patient received chemotherapy (VAC). The median follow-up was 3.9 years (range, 0.6-14.0 years). Three patients developed recurrent AF, including two recurrences after patients underwent incomplete resection without adjuvant treatment. Secondary resection was performed, which was incomplete in one patient who subsequently received chemotherapy (VAC). At the time of the current report, all 13 patients were in complete remission. Ten pediatric AF studies, including the current study, with a total of 187 patients were reviewed. Incomplete resection was the most important determinant for disease recurrence; in the authors' opinion, the role of adjuvant therapy needs to be studied further. CONCLUSIONS: Primary surgery with negative surgical margins was found to be the most successful primary treatment modality for children with AF. Positive margins after surgery indicated a high risk for disease recurrence. Multicenter, prospective (randomized) trials will be necessary to clarify the role of adjuvant treatment for patients with pediatric AF.

Resurgence of lymphogranuloma venereum in Western Europe: an outbreak of Chlamydia trachomatis serovar l2 proctitis in The Netherlands among men who have sex with men.

BACKGROUND: Lymphogranuloma venereum (LGV) is a sexually transmitted disease (STD) and is rare in the Western world. Recently, 3 men who have sex with men presented with LGV proctitis at the Erasmus Medical Center, Rotterdam, The Netherlands. We investigated a possible outbreak in a sexual network of men who have sex with men (MSM). METHODS: After active case finding, a total of 15 men presented and were investigated. Serum antibody titers to Chlamydia trachomatis were determined. Urine and rectum specimens were analyzed by polymerase chain reaction (PCR) for the presence of C. trachomatis. C. trachomatis-positive specimens were genotyped to detect the specific C. trachomatis serovars. All subjects underwent routine STD screening. Sociodemographic, clinical, and endoscopic characteristics were evaluated. RESULTS: Thirteen subjects had high immunoglobulin (Ig) G and IgA titers to C. trachomatis, suggesting an invasive infection. Rectal specimens of 12 subjects were PCR-positive for C. trachomatis. All urine specimens were negative. Genotyping revealed serovars L(2) (n=8) and L(1) (n=1). An ulcerative proctitis was found in all subjects obtaining sigmoidoscopy (n=9). Eleven of 13 subjects with an LGV diagnosis were seropositive for human immunodeficiency virus (HIV), 6 had another concomitant STD, and 1 had recently acquired a hepatitis C virus infection. Further sexual contacts were reported from The Netherlands, Germany, Belgium, the United Kingdom, and France. CONCLUSIONS: We revealed an outbreak of LGV proctitis among MSM in The Netherlands. The ulcerous character favors transmission of HIV, other STDs, and blood-borne diseases. From a public health perspective, it seems important to increase the awareness of possible LGV in MSM with symptomatic proctitis.

Prenatal testicular torsion: diagnosis and natural course. An ultrasonographic study.

The aim of this study was to demonstrate the ultrasonographic features of prenatal torsion of the testis at presentation and during follow-up, with histological correlation post-orchidectomy. Between January 1985 and December 1999, 13 neonates with antenatal torsion of the testis were examined postnatally, at presentation and during follow-up, with high-resolution ultrasonography, including colour Doppler ultrasonography. Bilateral testis volume was evaluated [lengthxwidthxdepthx(pi/6)]. Ultrasonographic findings were correlated with histological findings (n=8) and findings at surgery. Moreover, in 1 patient the affected testis was postoperatively examined with ultrasonography in vitro. These findings were correlated with preoperative ultrasonography and corresponding histological slices. All patients (n=13) presented with a painless congenital scrotal mass. On the affected side no flow was found with colour Doppler ultrasonography. Testis volume on the affected and normal side showed mean values of 2.1 and 0.5 cc, respectively. On ultrasonography all patients showed scrotal swelling and a heterogeneous testis with hypoechoic central areas (necrosis). The tunica albuginea was thickened in all patients, with focal (n=2) or rim-like (n=11) hyperechoic reflections (calcifications) at the transitional zone between testis and tunica albuginea. In 9 patients follow-up ultrasonography showed progressive testis atrophy on the affected side. In 10 patients a contralateral hydrocele was found. Prenatal torsion shows a characteristic ultrasonographic pattern. In newborns with a scrotal mass, these ultrasonographic findings should suggest this diagnosis and delay in immediate surgery and/or oncological work-up may be appropriate.

MR imaging of the brachial plexus: current imaging sequences, normal findings, and findings in a spectrum of focal lesions with MR-pathologic correlation.

Currently in many centers, magnetic resonance (MR) imaging is the technique of choice for the assessment of brachial plexopathies. The anatomy of the brachial plexus is complex, and is surrounded by other anatomic structures, making artifact-free imaging quite challenging. With the faster breathing-independent and breath-hold MR imaging sequences, brachial plexopathies can be assessed with more confidence. Over a 2-year period, 20 patients underwent MR imaging of the brachial plexus at our department. MR imaging was based on a comprehensive protocol, including T(1)-weighted gradient echo, T(2)-weighted single-shot fast spin-echo, and gadolinium-enhanced T(1)-weighted gradient echo with fat suppression. Nine of the 20 patients had proved diagnoses at pathology, and included schwannoma (n = 2), ganglioneuroblastoma (n = 1), hemangioma (n = 1), metastatic breast cancer (n = 2), Pancoast tumor (n = 1), and metastatic lung cancer (n = 2). Most of the lesions had presenting symptoms, such as pain, swelling, paresthesia, and arm weakness. At MR imaging, the location and characteristics of the lesions on different types of T(1)-weighted and T(2)-weighted sequences were described with pathologic correlation.