High-risk clinical stage I nonseminomatous germ cell tumors: the case for chemotherapy

Testis cancer is the most frequent solid malignancy in young men. The majority of patients present with clinical stage I disease and about 50% of them are nonseminomatous germ cell tumors. In this initial stage of disease there is a subgroup of patients at high risk with a likelihood of more than 50% for relapse. Treatment options for these patients include: retroperitoneal lymph node dissection (RPLND), albeit 6-10% of patients will relapse outside the field of RPLND, active surveillance with even higher relapse rates and adjuvant chemotherapy. As most of these patients have the chance to become long-term survivors, avoidance of long-term side effects is of utmost importance. This review provides information on the potential of chemotherapy to achieve a higher chance of cure for patients with high-risk clinical stage I disease than its therapeutic alternatives and addresses toxicity and dose dependency.

Occurrence of Leishmania sp. in cutaneous lesions of horses in Central Europe

The present report describes a novel etiological agent of cutaneous leishmaniasis in horses that, at least for some cases, sporadically appeared as autochthonous infections in geographically distant regions of Germany and Switzerland. The infection was initially diagnosed upon clinical and immunohistological findings. Subsequent comparative sequence analysis of diagnostic PCR products from the internal transcribed spacer 1 (ITS1) of ssrRNA classified the respective isolates as neither Old World nor New World Leishmania species. However, four isolates subjected to molecular analyses all exhibited a close phylogenetic relationship to Leishmania sp. siamensis, an organism recently identified in a visceral leishmaniasis patient from Thailand. Future investigations will demonstrate if this form of leishmaniasis represents an emerging, and perhaps zoonotic, disease of European, or even global, importance.

Non-selective cutaneous sensory neurectomy as an alternative treatment for auto-mutilation lesion following arthrodesis in three dogs

OBJECTIVE: To describe an alternative method for the treatment of non-responsive self-mutilation injuries in three dogs after carpal/tarsal arthrodesis. STUDY DESIGN: Case series ANIMALS: Two dogs with carpal injury and one dog with tarsal injury treated by arthrodesis METHODS: All dogs developed self-mutilation injuries due to licking and/or chewing of the toes within 21-52 days of surgery. Clinical signs did not resolve within one week after conservative treatment with wound debridement and protective bandages. Following general anaesthesia, a deep horseshoe-shaped skin incision, including the subdermal tissue, was performed proximal to the self-mutilation injury transecting the sensory cutaneous afferent nerves. The skin incision was closed with simple interrupted sutures. RESULTS: All wounds healed without complication. Self-mutilation resolved completely within 24 hours after surgery in all dogs. No recurrence was observed (5 months to 3 years). CONCLUSION: Non-selective cutaneous sensory neurectomy may lead to resolution of self-mutilation following arthrodesis in dogs. CLINICAL RELEVANCE: Failure of conservative treatment in self-mutilation injuries often leads to toe or limb amputation as a last resort. The technique described in this case series is a simple procedure that should be considered prior to amputation. The outcome of this procedure in dogs self-multilating due to neurological or behavioral disturbances unrelated to carpal or tarsal arthrodesis is not known.

Porcine ulcerative dermatitis syndrome in sows: a form of vesicular cutaneous lupus erythematosus?

Severe ulcerative lesions were observed in the skin of two sows in a herd of 540 hybrid sows. Annular to polycyclic, severe crusting dermal ulcerations were found on the abdomen and flanks; moderate lesions were also found at the base of the tail and on the perineum. The lesions were histologically characterised as cell-poor interface dermatitis and folliculitis, basal cell vacuolisation, vesicle formation at the dermal-epidermal junction and serocellular crusts. A subepidermal mild to moderate band, characterised as a mixed inflammatory infiltrate, was present. A test for antinuclear antibodies was negative; however, immunofluorescence testing revealed a linear pattern of IgG precipitation in the skin. Staphylococcus hyicus was demonstrated in the serocellular crusts of one sow. Treatment with antibiotics, topical antiseptics and corticosteroids did not improve the sows' condition. Porcine circovirus and porcine respiratory and reproductive syndrome virus were not isolated from samples taken at postmortem examination. The observed gross lesions, the absence of response to treatment and the exclusion of other skin diseases suggested that the sows were affected with porcine ulcerative dermatitis syndrome.

Patients with oral tumors. Part 2: Quality of life after treatment with resection prostheses. Resection prosthetics: evaluation of quality of life

In the present study, the oral health-related quality of life of 18 patients (13 men and 5 women) was evaluated using validated questionnaires as proposed by the European Organization of Research and Treatment of Cancer (EORTC). The patients belonged to a cohort of 48 patients, whose prosthetic treatment was performed during the years 2004-2007. In the course of tumor resection, 12 patients underwent graft surgery and 14 patients radiotherapy. One patient required a nasal epithesis since resection of the nose became necessary. Five patients underwent a full block resection of the mandible, and tumor resection in 3 patients resulted in a large oronasal communication. Prosthetic rehabilitation was performed in all patients, and the follow-up period with regular care covered a minimum of 3 years. Eleven patients received dental implants for better support and retention of the prostheses. In spite of compromised oral conditions, functional restrictions, and some difficulties with the prostheses, the answers to the questionnaire were quite positive. The majority judged their general health as good or even excellent. The subjective perception of the patients may contradict the objective view by the dentist. In fact, the individual patient's history and experience provide a better understanding of the impact of oral tumors on daily life. The overall assessment identified 4 items that were perceived as major problems by all patients: swallowing solid food, dry mouth, limited mouth opening, and appearance. Prosthetic rehabilitation has only a limited influence on such problems.

Patients with oral tumors. Part 1: Prosthetic rehabilitation following tumor resection. Resection prosthetics: surgery, implants and prosthetic treatment

The present study reports on the surgical and prosthodontic rehabilitation of 46 patients, 31 male and 15 female, after resection of oral tumors. The treatment was carried out from 2004 to 2007 at the Department of Prosthodontics, University of Bern, with a follow-up time of 3 to 6 years. The average age at diagnosis was 54 years. 76% of all tumors were squamous cell carcinoma, followed by adenocarcinoma. Resection of the tumors including soft and/or hard tissues was performed in all patients. 80% of them additionally underwent radiotherapy and 40% chemotherapy. A full block resection of the mandible was perfomed in 23 patients, and in 10 patients, the tumor resection resulted in an oronasal communication. 29 patients underwent grafting procedures, mostly consisting of a free fibula flap transplant. To enhance the prosthetic treatment outcome and improve the prosthesis stability, a total of 114 implants were placed. However, 14 implants were not loaded because they failed during the healing period or the patient could not complete the final treatment with the prostheses. The survival rate of the implants reached 84.2% after 4 to 5 years. Many patients were only partially dentate before the tumors were detected, and further teeth had to be extracted in the course of the tumor therapy. Altogether, 31 jaws became or remained edentulous. Implants provide stability and may facilitate the adaptation to the denture, but their survival rate was compromised. Mostly, patients were fitted with removable prostheses with obturators in the maxilla and implant-supported complete dentures with bars in the mandible. Although sequelae of tumor resection are similar in many patients, the individual intermaxillary relations, facial morphology and functional capacity vary significantly. Thus, individual management is required for prosthetic rehabilitation.

Anticancer activity of anandamide in human cutaneous melanoma cells

Cannabinoids are implicated in the control of cell proliferation, but little is known about the role of the endocannabinoid system in human malignant melanoma. This study was aimed at characterizing the in vitro antitumor activity of anandamide (AEA) in A375 melanoma cells. The mRNA expression of genes that code for proteins involved in the metabolism and in the mechanism of AEA action was assessed by RT-PCR. Cell viability was tested using WST-1 assay and the apoptotic cell death was determined by measuring caspase 3/7 activities. A375 cells express high levels of fatty acid amide hydrolase (FAAH), cyclooxygenase (COX)-2, cannabinoid receptor 1 (CB1), transient receptor potential cation channel subfamily V member 1 (TRPV1) and G-protein-coupled receptor 55 (GPR55) genes. AEA induced a concentration-dependent cytotoxicity with an IC50 of 5.8±0.7 µM and such an effect was associated to a caspase-dependent apoptotic pathway. AEA cytotoxicity was potentiated by FAAH inhibition (2-fold increase, p<0.05) and mitigated by COX-2 or lipoxygenase (LOX) inhibition (5- and 3-fold decrease, respectively; p<0.01). Blocking CB1 receptors partially decreased AEA cytotoxicity, whereas selective antagonism on the TRPV1 barely affected the mechanism of AEA action. Finally, methyl-β-cyclodextrin, a membrane cholesterol depletory, completely reversed the cytotoxicity induced by the selective GPR55 agonist, O-1602, and AEA. Overall, these findings demonstrate that AEA induces cytotoxicity against human melanoma cells in the micromolar range of concentrations through a complex mechanism, which involves COX-2 and LOX-derived product synthesis and CB1 activation. Lipid raft modulation, probably linked to GPR55 activation, might also have a role.

TH2 cytokines from malignant cells suppress TH1 responses and enforce a global TH2 bias in leukemic cutaneous T-cell lymphoma

PURPOSE In leukemic cutaneous T-cell lymphoma (L-CTCL), malignant T cells accumulate in the blood and give rise to widespread skin inflammation. Patients have intense pruritus, increased immunoglobulin E (IgE), and decreased T-helper (TH)-1 responses, and most die from infection. Depleting malignant T cells while preserving normal immunity is a clinical challenge. L-CTCL has been variably described as a malignancy of regulatory, TH2 and TH17 cells. EXPERIMENTAL DESIGN We analyzed phenotype and cytokine production in malignant and benign L-CTCL T cells, characterized the effects of malignant T cells on healthy T cells, and studied the immunomodulatory effects of treatment modalities in patients with L-CTCL. RESULTS Twelve out of 12 patients with L-CTCL overproduced TH2 cytokines. Remaining benign T cells were also strongly TH2 biased, suggesting a global TH2 skewing of the T-cell repertoire. Culture of benign T cells away from the malignant clone reduced TH2 and enhanced TH1 responses, but separate culture had no effect on malignant T cells. Coculture of healthy T cells with L-CTCL T cells reduced IFNγ production and neutralizing antibodies to interleukin (IL)-4 and IL-13 restored TH1 responses. In patients, enhanced TH1 responses were observed following a variety of treatment modalities that reduced malignant T-cell burden. CONCLUSIONS A global TH2 bias exists in both benign and malignant T cells in L-CTCL and may underlie the infectious susceptibility of patients. TH2 cytokines from malignant cells strongly inhibited TH1 responses. Our results suggest that therapies that inhibit TH2 cytokine activity, by virtue of their ability to improve TH1 responses, may have the potential to enhance both anticancer and antipathogen responses.