Verrucous carcinoma of the esophagus - a case report and literature review.

BACKGROUND: Verrucous carcinoma of the esophagus is a rare disease leading to dysphagia, chest pain, and weight loss. The diagnosis is difficult because even repeated biopsies are often without tumor evidence. We present a patient with verrucous carcinoma of the esophagus and a literature review. CASE REPORT: A 64-year-old patient with dysphagia and sore throat received esophagogastroduodenoscopy illustrating segmental circumferential verrucous inflammation and Candida esophagitis in the middle part of the esophagus. Repeated mucosal biopsies revealed reactive hyperkeratosis of the squamous epithelium with minimal atypia but without ulcera, eosinophilic esophagitis, or suspicion of cancer. Mucosal infection with adenovirus, herpes simplex virus 1, human papilloma virus types, and cytomegaly virus was ruled out. Veruccous carcinoma was detected finally by endoscopic mucosal resection. The patient was successfully treated by esophageal resection. Tumor stage was G1, pT1b, pN0, L0, V0, Pn0, R0. CONCLUSION: The results suggest that macroscopic suspicion of verrucous esophageal carcinoma should lead to resections of larger tissue specimens by EMR to confirm the diagnosis.

Autoimmune encephalitis and gastrointestinal dysmotility: achalasia, gastroparesis, and slow transit constipation.

BACKGROUND: Neurological autoimmune disorders (NAD) are caused by autoimmune inflammation triggered by specific antibody subtypes. NAD may disturb the gut-brain axis at several levels including brain, spinal cord, peripheral, or enteric nervous system. CASE REPORT: We present a case with antinuclear neuronal Hu (ANNA-1)- and antiglial nuclear (SOX-1) autoimmune antibody-positive limbic encephalitis and significant gastrointestinal dysmotility consisting of achalasia type II, gastroparesis, altered small intestinal interdigestive motility, and severe slow transit constipation. The autoantibodies of the patient's serum labeled enteric neurons and interstitial cells of Cajal but no other cells in the gut wall. Achalasia was treated successfully by pneumatic cardia dilation and gastrointestinal dysmotility successfully with prucalopride. CONCLUSION: NAD may disturb gastrointestinal motility by altering various levels of the gut-brain axis.

Sexual intraspecific recombination but not de novo origin governs the genesis of new apomictic genotypes in Potentilla puberula (Rosaceae).

Apomixis - asexual reproduction via seeds - might arise de novo following polyploidisation events, or via reproductive transfer of apomixis. Both processes can be obtained within species or via hybridisation. We aimed to determine the origin of apomictic genotypes in Potentilla puberula, a rosaceous species showing reproductive differentiation with ploidy: sexual tetraploids and apomictic penta- to octoploids, which regularly co-occur in sympatry. The study is based on 726 individuals, comprising all cytotypes, collected from 138 populations in the Eastern European Alps. We established relationships of cytotypes based on AFLP fingerprinting and cpDNA sequencing to test (1) whether the apomicts are of recurrent allopolyploid origin or originated from within the species via autopolyploidy, and (2) whether there are indications for reproductive transfer versus de novo origin of apomixis. Three principal pathways were identified which explain the origin of new apomictic genotypes, all involving at least one apomictic parent and thus compatible with the idea of reproductive transfer of the apomictic trait to the progeny: (1) self-fertilisation of unreduced egg cells in apomicts; (2) cross-fertilisation among apomicts; and (3) occasionally, heteroploid crosses among sexuals and apomicts. Autopolyploids derived from tetraploid sexuals were repeatedly observed, but did not express apomixis. Finally, our results suggest no role of other species in the origin of extant apomictic genotypes of P. puberula, although local hybrids with P. crantzii were identified. In conclusion, our results show that the formation of new apomictic genotypes required a genetic contribution from at least one apomictic parent. This finding is in accordance with the idea that apomixis is inheritable in P. puberula. On the contrary, lack of apomixis in penta- and hexaploids derived from sexual backgrounds did not support the hypothesis of a de novo origin of apomixis. Relatively high frequency of remnant sexuality in the apomicts involving different cytological pathways of seed formation can explain their high cytological and genotypic diversity. Finally, lack of global introgression from a third taxon is in support of P. puberula as a concise, although highly diverse, species.

RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis.

Cell fate decisions during haematopoiesis are governed by lineage-specific transcription factors, such as RUNX1, SCL/TAL1, FLI1 and C/EBP family members. To gain insight into how these transcription factors regulate the activation of haematopoietic genes during embryonic development, we measured the genome-wide dynamics of transcription factor assembly on their target genes during the RUNX1-dependent transition from haemogenic endothelium (HE) to haematopoietic progenitors. Using a Runx1-/- embryonic stem cell differentiation model expressing an inducible Runx1 gene, we show that in the absence of RUNX1, haematopoietic genes bind SCL/TAL1, FLI1 and C/EBPß and that this early priming is required for correct temporal expression of the myeloid master regulator PU.1 and its downstream targets. After induction, RUNX1 binds to numerous de novo sites, initiating a local increase in histone acetylation and rapid global alterations in the binding patterns of SCL/TAL1 and FLI1. The acquisition of haematopoietic fate controlled by Runx1 therefore does not represent the establishment of a new regulatory layer on top of a pre-existing HE program but instead entails global reorganization of lineage-specific transcription factor assemblies.

Ultrasound technology in dermatology.

As a noninvasive diagnostic method, real-time B-mode sonography belongs to the diagnostic standard procedures in various fields of clinical medicine, for example, internal medicine, gynecology, and otorhinolaryngology. During the past 3 decades, ultrasound technology has been extended to clinical dermatology. High-frequency ultrasound systems with 20- to 50-MHz probes are used for the assessment of tumoral and inflammatory processes of the skin, providing information about their axial and lateral extension. They are of special interest in preoperative situations and for the monitoring of skin conditions under therapy. In contrast to high-frequency ultrasound systems, the value of ultrasound technology with the use of 7.5- to 15-MHz probes generally is not accepted worldwide, although it can be used easily and without significant side effects. Promising results have been reported from specialized diagnostic centers, especially for the assessment of peripheral lymph nodes and soft-tissue tumors. Although it is unable to provide malignancy specific information, ultrasound is nonetheless helpful in the follow-up of patients undergoing, for example, chemotherapy or radiotherapy. The 3-dimensional size and outline of a tumor as well as its relation to surrounding structures like vessels can be described. Moreover, information about the tumor quality (solid, cyst, complex) and the inner structure of a tumor (hypoechoic, hyperechoic, homogenous, inhomogenous, calcification foci, necroses) can be provided. In addition to conventional B-mode-sonography, newer ultrasound techniques like native and signal-enhanced color Doppler sonography as well as ultrasound-guided fine needle aspiration cytology are reviewed.

Ultrasonography in dermatology.

Ultrasonography is an essential tool for most medical specialties; training in its use is required for dermatology residency programs in Germany. Ultrasonography is a versatile, painless, low-risk, non-invasive procedure which can be done anywhere and easily repeated; it provides real-time visual information about benign and malignant processes in the skin and subcutis. High frequency sonography with 20 MHz scanners is well-established for measuring the thickness of the skin or its tumors and assessing inflammatory skin disorders. Mid-frequency sonography with 7.5-15 MHz sounds is widely used in dermatologic oncology, both for pre-operative staging and follow-up of melanoma patients. The interpretation of sonographic images such as borders of lesions, echogenicity, artifacts and vascular patterns with duplex color sonography requires structured education and intensive training. The wide variety of diagnostic information provided by sonography underlines its essential position in certified skin cancer centers.

Growth inhibition of multiresistant enterococci by interferon-gamma-activated human uro-epithelial cells.

Nosocomial infections with enterococci are an increasing problem in modern medical practice due to the development of resistance to a wide range of antibiotics, including the glycopeptides vancomycin and teicoplanin. An increasing number of vancomycin-resistant enterococci (VRE) have been cultured from clinical specimens -- especially from patients undergoing immunosuppressive therapy -- and bacteraemia caused by these VRE, subsequent to colonisation of epithelial surfaces, is a significant cause of mortality in such patients. Recent evidence showed that the induction of indoleamine 2,3 dioxygenase (IDO) by interferon-gamma (IFN-gamma) inhibited growth of group B streptococci by depleting the essential amino acid L-tryptophan. This study describes the IFN-gamma-induced expression of IDO -- shown at a transcriptional level by Northern blot analysis, at translational level by Western blot and also at a functional level by L-tryptophan degradation to L-kynurenine -- in the uro-epithelial cell line RT4. The depletion of L-tryptophan resulted in growth inhibition of enterococci, and this was confirmed by abrogation of the inhibitory effect by re-supplementation with excess L-tryptophan. Multiresistant enterococci, including vancomycin-resistant strains resistant to all commercially available antibiotics, were inhibited by the IFN-gamma-induced expression of IDO and subsequent L-tryptophan degradation. This may be an important mechanism in the local restriction of colonisation of the urinary tract by endogenous enterococci and in inhibiting the spread of the bacteria beyond the epithelial barrier.

Lymph node metastases in patients with cutaneous melanoma: improvements in diagnosis by signal-enhanced color Doppler sonography.

The purpose of the study was to evaluate whether signal-enhanced color Doppler sonography (CDS) is superior to native CDS in detection of characteristic vascularity patterns that are important for the differentiation between benign and malignant lymphadenopathy in patients with cutaneous melanomas. Twenty-two melanoma patients presenting with 24 structures suspicious for metastases in B-Mode sonography were examined using native and signal-enhanced CDS in a prospective two-center study. Presumptive sonographic diagnoses were compared with results of histopathological and follow-up examinations. Signal-enhanced CDS gave additional information about vascularization of lymph node metastases and reactive lymph nodes, which was indicative for the differential diagnosis in 12 of 24 examinations. For lymph node metastases, signal enhancement improved the visualization of accessory peripheral vessels in four of 10 examinations. Concerning reactive lymph nodes, hilar vessels in part with branching to the lymph node periphery could be better identified after application of the contrast enhancer in eight of 13 examinations. Signal-enhanced CDS is demonstrated as an important additional diagnostic tool for improved differentiation between malignant and reactive lymph nodes and may be of special value in preventing unnecessary lymphadenectomy in small reactive lymph nodes.

Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients.

BACKGROUND: Although botulinum toxin type A (BoNT-A) is a common aesthetic intervention, there are few published data on treatment over more than two cycles. OBJECTIVE: To evaluate the effectiveness/safety of repeated doses of BoNT-A (Dysport, Ipsen Ltd., Slough, UK) in the upper face for reduction of wrinkles. METHODS: Retrospective, cross-sectional patient chart review from 945 patients who had received a minimum of three consecutive, documented treatment cycles. RESULTS: The glabella was treated most frequently (93.9%), with the majority (81.5%) of patients receiving treatment in more than one area of the face. BoNT-A treatments were combined with other aesthetic procedures in 57.5% of cases, mostly with fillers (37.1%). There was no evidence of tachyphylaxia: the dose applied, the interval between treatments, and satisfaction with the results remained stable over the course of treatment. Adverse events were those expected with BoNT-A treatment (most common: local bruising and ptosis) and were all mild or moderate in intensity. There was no sign of any cumulative adverse effects: indeed, the adverse-event rate decreased in later treatment cycles. CONCLUSIONS: Long-term, repeated injections of BoNT-A for corrections of wrinkles in the upper face yield a continuously high level of safety and effectiveness in actual practice.

Ultrasound mapping of lymph node and subcutaneous metastases in patients with cutaneous melanoma: results of a prospective multicenter study.

BACKGROUND: Ultrasound (sonography, B-mode sonography, ultrasonography) examination improves the sensitivity in more than 25% compared to the clinical palpation, especially after surgery on the regional lymph node area. OBJECTIVE: To evaluate the distribution of metastases during follow-up in the draining lymph node areas from the scar of primary to regional lymph nodes (head and neck, supraclavicular, axilla, infraclavicular, groin) in patients with cutaneous melanoma with or without sentinel lymph node biopsy (SLNB) or former elective or consecutive complete lymph node dissection in case of positive sentinel lymph node (CLND). cv: Prospective multicenter study of the Departments of Dermatology of the Universities of Homburg/Saar, Tubingen and Munich (Germany) in which the distribution of lymph node and subcutaneous metastases were mapped from the scar of primary to the lymphatic drainage region in 53 melanoma patients (23 women, 30 men; median age: 64 years; median tumor thickness: 1.99 mm) with known primary, visible lymph nodes or subcutaneous metastases proven by ultrasound and histopathology during the follow-up. RESULTS: Especially in the axilla, infraclavicular region and groin the metastases were not limited to the anatomic lymph node regions. In 5 patients (9.4%) (4 of them were in stage IV) lymph node metastases were not located in the corresponding lymph node area. 32 patients without former SLNB had a time range between melanoma excision and lymph node metastases of 31 months (median), 21 patients with SLNB had 18 months (p < 0.005). In 11 patients with positive SLNB the time range was 17 months, in 10 patients with negative SLNB 21 months (p < 0.005); in 32 patients with CLND the time range was 31 months and in 21 patients without CLND 18 months (p<0.005). In thinner melanomas lymph node metastases occurred later (p<0.05). CONCLUSIONS: After surgery of cutaneous melanoma, SLNB and CLND the lymphatic drainage can show significant changes which should be considered in clinical and ultrasound follow-up examinations. Especially for high-risk melanoma patients follow-up examinations should be performed at intervals of 3 months in the first years. Patients at stage IV should be examined in all regional lynph node areas clinically and by ultrasound.

Somatic mosaicism of chromosome 7 in a highly proliferating melanocytic congenital naevus in a ring chromosome 7 patient.

Ring chromosome 7 is a rare but well documented chromosomal aberration in man. So far at least 14 cases have been reported in the literature showing a variable but distinct pattern of phenotypic characteristics in affected individuals. Besides others, skin findings as pigmented naevi are especially frequent. Loss of chromosomal material from the terminal chromosome arms in the structurally abnormal ring chromosome 7 as well as somatic mosaicism with loss or gain of chromosome 7 has been suggested to be responsible for the clinical symptoms. We now report another case of a ring chromosome 7 in a 14-year-old boy with multiple remarkable congenital naevi, where we could demonstrate for the first time somatic mosaicism showing significant gain of chromosome 7 within a highly proliferating melanocytic congenital naevus (MCN).