Langerhans cell histiocytosis as differential diagnosis of a mediastinal tumor

We describe the case of a 55-year-old man who presented with parasternal swelling. The chest CT scan showed a large tumor of the chest wall infiltrating the subcutaneous tissue. To assume histologic diagnosis an open biopsy was performed. Between the myofibrils a coarse, white tumor with infiltrative growth was noted. Histopathologic examination revealed expanded atrophic skeletal muscle that was infiltrated by histiocytic cells. Numerous eosinophilic granulocytes and lymphocytes CD20 and CD3 positive could be detected and immunohistochemical staining was also positive for S-100 proteins and CD1a. Histologic findings were characteristic of Langerhans cell histiocytosis (LCH). To the best of our knowledge a LCH originating from the mediastinum in an adult as presented has not been previously describe

Effect of pregnancy and birth on the course of myasthenia gravis before or after transsternal radical thymectomy

Objective: Myasthenia gravis (MG) affects women at childbearing age. Therefore, the question arises if these patients should become pregnant and if thymectomy has a positive effect on the course of MG in pregnant patients. Methods: Fifteen pregnancies had been followed retrospectively. All patients underwent transsternal radical thymectomy for MG. The course of MG in the period before, during, and after the pregnancy was scored according to Ossermann's classification. The effect of thymectomy on delivery and on the newborns was evaluated. Results: Patients were divided in two groups: pregnancies before (group I, n = 8) and after (group II, n = 7) thymectomy. During pregnancy, in group I, one deterioration was observed and in seven patients the disease was unchanged. In group II, one deterioration, five unchanged courses, and one improvement were observed. In the postpartum period, in group I, seven patients did not change and one improved. In group II, two deteriorations, three unchanged courses, and two improvements were observed. Before pregnancy, group II patients were in a better Ossermann stage in comparison with those in group I. Eight of the 12 deliveries were spontaneous (three abortus). Myasthenic symptoms were observed in two newborns in group I. Conclusion: Our data suggest that MG is not prohibitive to have children. The course of MG after transsternal radical thymectomy is often ameliorated. A better MG-stage, reached after thymectomy, before pregnancy seems to be correlated with a better course during pregnanc

High expression of octamer-binding transcription factor 4A, prominin-1 and aldehyde dehydrogenase strongly indicates involvement in the initiation of lung adenocarcinoma resulting in shorter disease-free intervals†

OBJECTIVES The increasing relevance of the cancer stem cell (CSC) hypothesis and the impact of CSC-associated markers in the carcinogenesis of solid tumours may provide potential prognostic implications in lung cancer. We propose that a collective genetic analysis of established CSC-related markers will generate data to better define the role of putative CSCs in lung adenocarcinoma (LAC). METHODS Sixty-four paired tumour and non-tumour biopsies from LAC patients were included in this study. Using the quantitative reverse transcriptase-polymerase chain reaction, we assessed the expression profiles of established CSC-related biomarkers: octamer-binding transcription factor 4 (OCT4A), CD133, aldehyde dehydrogenase (ALDH), BMI-1, ATP-binding cassette subfamily G, member 2 (ABCG2), SRY (sex-determining region Y)-box 2 (SOX2) and uPAR, and evaluated their relation to clinicopathological parameters and disease prognosis. RESULTS All of the above-mentioned CSC-related markers were detectable in both tumour and corresponding normal tissues. Importantly, expression levels of OCT4A, CD133, BMI-1, SOX2 and uPAR were significantly higher (OCT4A, P=0.0003; CD133, P=0.002; BMI-1, P=0.04; SOX2, P=0.0003; uPAR, P=0.03) in the tumour compared with those in the non-tumour tissues. By contrast, the quantities of ACBG2 and ALDH were markedly reduced (ACBG2, P=0.0006; ALDH, P=0.007) in the tumour relative to those in the normal biopsies. Using multivariate analysis, elevated ALDH and CD133 revealed significant associations in tumour stage (ALDH, P=0.03; CD133, P=0.007) and differentiation (ALDH, P=0.03; CD133, P=0.018). We observed that ALDH and OCT4A were associated with nodal status (ALDH, P=0.05; OCT4A, P=0.03) having lower mRNA levels in tumours with lymph node metastasis, N+, compared with that in N0. High OCT4A levels were significantly correlated with tumour size of 3cm (P=0.03). Kaplan-Meier correlation analyses, showed that OCT4A and CD133 were correlated to short disease-free intervals (OCT4A, P=0.047; CD133, P=0.033) over a period of 29 months. CONCLUSIONS Our study reveals that CSC-associated markers: OCT4A, CD133 and ALDH are involved in the initial phase of carcinogenesis of LAC, and can be used as predictors of early stage LAC and poor disease-free intervals. In addition, this work validates the relevance of the CSC hypothesis in LA

Comparison of procalcitonin and CrP in the postoperative course after lung decortication

Objective: The objective of this prospective study was to compare the clinical value of procalcitonin (PCT) and C-reactive protein (CrP) plasma concentrations in their postoperative course after decortication. Methods: Twenty-two patients requiring surgery for pleural empyema were chosen for this prospective study. Routine blood samples including CrP and PCT plasma concentrations were taken before the operation and on the 1st, 2nd, 3rd, and 7th postoperative day. Results: Due to infection PCT and CrP were elevated preoperatively. In the postoperative course both PCT and CrP reached peak-levels on day 2 with values up to 43.55ng/ml and 384.00mg/l, respectively. In PCT the rise was followed by a clear decrease in 20 (90.9 %) patients until day 7. In contrast the CrP levels decreased slowly and only seven (54.5%) patients had values of 100mg/l or below on day 7. PCT showed a better correlation with the clinic in case of septic course than CrP does. Conclusions: PCT reflects postoperative clinical course more accurately than CrP. Therefore, PCT is a more appropriate laboratory parameter to monitor patients after surgery for pleural empyem

1,25-Dihydroxycholecalciferol with low-calcium diet reduces acute rejection in rat lung allotransplantation

OBJECTIVES The effect of 1,25-dihydroxycholecalciferol (calcitriol, vitamin D3) with a low-calcium diet on the acute lung allograft rejection in a rat unilateral left lung transplantation model was evaluated. METHODS Three transplantation groups were studied (n=5, male Brown-Norway to Fischer F344, 235±15g body weight): calcitriol and low-calcium diet, low-calcium diet and normal diet. Calcitriol (4μg/kg/day) was injected intraperitoneally for 5 days, starting from the day of transplantation. In addition, two non-transplantation groups were compared: (n=3, Brown-Norway) to measure the level of cytokines, and Fischer F344 receiving calcitriol and a low-calcium diet to measure the serum calcium level. The recipients of transplantation were killed on Day 5 post-transplant. The contralateral right main bronchus and the pulmonary artery were occluded for 5min and blood was drawn for the blood gas analysis, and the grafts were assessed for histology (International Society for Heart and Lung Transplantation 1996/rank scale). Lung levels of interleukin (IL)-2, IL-6, IL-12 and tumour necrosis factor-α (TNF-α) were assessed within the calcitriol and low-calcium diet, low-calcium diet and Brown-Norway groups. The serum calcium level was assessed in the Fischer F344 group. An analysis of variance with Tukey's post hoc test was used to compare the arterial blood oxygen pressure and the lung cytokine expression between groups. A non-parametric Kruskal-Wallis test followed by the Siegel and Castellan post hoc test was used to assess the differences between the groups according to the lung graft rejection grading. Student's paired t-test was used to compare the serum calcium level. RESULTS The arterial PaO2 was significantly higher in the calcitriol and the low-calcium diet groups when compared with low-calcium diet or normal diet groups (356±72mmHg; P<0.05 vs other groups). The arterial and bronchial rejection observed in calcitriol and low-calcium diet group was significantly milder than in the low-calcium diet or normal diet groups (A1-2, B1-2; P<0.05 vs other groups). IL-2 and IL-6 levels were significantly higher in low-calcium diet vs calcitriol and low-calcium diet and Brown-Norway groups. IL-12 and TNF-α did not differ among the groups. There was no significant difference in serum calcium level before and after the treatment in the Fischer F344 group. CONCLUSIONS Calcitriol with a low-calcium diet treatment improves lung function, reduces lung allograft acute rejection, decreases IL-2 and IL-6 allograft expression and does not change the serum calcium level significantl

Taurolidine in the prevention and therapy of lung metastases

Objective: During surgery for colon carcinoma, tumour cells may spread into the blood and may lead to the development of distant metastases. The most frequent sites of metastases are the liver and lungs. A new therapeutic approach is required to prevent tumour implantation of freely circulating tumour cells during and after surgery and to treat established metastases. The aim of this prospective study was to observe the influence of long-term intravenous taurolidine on the development of lung metastases after intravenous injection of colon adenocarcinoma cells. Methods: Tumour cells (DHD/K12/TRb colon adenocarcinoma cell line, 1×106 cells) were injected into the right vena jugularis interna of BDIX rats. The animals (n=13) were randomised into three groups: group 1: tumour cell implantation without taurolidine application (control group); group 2: tumour cell implantation and simultaneous start of the taurolidine injection through osmotic pump, removal of the osmotic pump on day 7; group 3: tumour cell implantation on day 0 and start of the taurolidine injection through osmotic pump on day 14. Results: In the taurolidine groups, the number and size of lung metastases were significantly lower compared to the control group (p=0.018; p=0.018 and p=0.036; p=0.018). Although the results of the intravenous long-term therapy with taurolidine in group 2 did not reach statistical significance in comparison with the results of group 3, a positive trend was revealed: The mean number of metastases in group 2 was 18.2 versus 28.2 in group 3. Conclusions: The application of taurolidine tends to prevent the development of lung metastases. Furthermore, taurolidine seems to reduce established lung metastases in this in vivo model. Taurolidine may offer additional therapeutic options in patients with colon adenocarcinom

Strong additive effect of 1,25-dihydroxycholecalciferol and cyclosporine A but not tacrolimus in rat lung allotransplantation

Objectives: 1,25-Dihydroxycholecalciferol (calcitriol, vitamin D3) has immunosuppressive properties. This study evaluates the effect of calcitriol in combination with either cyclosporine A or tacrolimus on acute lung allograft rejection in a rat model of unilateral left lung allotransplantation. Methods: Unilateral left lung transplantation was performed in male rats (Brown-Norway to Fischer F344, 200-250 g body weight). For immunosuppression, the following subtherapeutic doses were used: calcitriol 0.5 μg/kg/day, cyclosporine A 2.5 mg/kg/day i.p., and tacrolimus 40 μg/kg i.m. Five groups (n=5) were analyzed: cyclosporine A; cyclosporine A and calcitriol; calcitriol; tacrolimus and calcitriol; and tacrolimus. The injections were performed for 5 days starting from the day of transplantation. Recipients were sacrificed on day 5 post-transplant. The contralateral right main bronchus and pulmonary artery were occluded for 5 min and blood was drawn for blood gas analysis. The grafts were excised, fixed in formaline and embedded in paraffin. Histological evaluation was done in blinded fashion (ISHLT 1999/rank scale). The mean and standard error of the mean (PaO2) or the median and range (rejection grading) are given. ANOVA followed by planned comparison for the PaO2 and Kruskal-Wallis ANOVA for rejection grading were applied, p<0.05 considered significant. Results: Arterial PaO2 on day 5 was very low in animals treated with subtherapeutic dosages of either cyclosporine A (48±10 mmHg), calcitriol (51±3) or tacrolimus (86±22). Combined treatment with cyclosporine A and calcitriol revealed a significant improvement (248±78; p<0.05 vs. other groups), whereas the combination of tacrolimus with calcitriol did not reveal any benefit (65±9). Rejection grading with these subtherapeutic doses did not show any significant difference between groups. Conclusions: Our data indicate that cyclosporine A, but not tacrolimus, has a strong additive effect with calcitriol on acute rat lung allograft rejectio

Schedule-Dependent Treatment Increases Chemotherapy Efficacy in Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare but aggressive thoracic malignancy with limited treatment options. One of the standard treatments for MPM is chemotherapy, which consists of concurrent treatment with pemetrexed and cisplatin. Pemetrexed limits tumor growth by inhibiting critical metabolic enzymes involved in nucleotide synthesis. Cisplatin causes direct DNA damage, such as intra-strand and inter-strand cross-links, which are repaired by the nucleotide excision repair pathway, which depends on relatively high nucleotide levels. We hypothesized that prolonged pretreatment with pemetrexed might deplete nucleotide pools, thereby sensitizing cancer cells to subsequent cisplatin treatment. The MPM cell lines ACC-MESO-1 and NCI-H28 were treated for 72 h with pemetrexed. Three treatment schedules were evaluated by initiating 24 h of cisplatin treatment at 0 h (concomitant), 24 h, and 48 h relative to pemetrexed treatment, resulting in either concomitant administration or pemetrexed pretreatment for 24 h or 48 h, respectively. Multicolor flow cytometry was performed to detect γH2AX (phosphorylation of histone H2AX), a surrogate marker for the activation of the DNA damage response pathway. DAPI staining of DNA was used to analyze cell cycle distribution. Forward and side scatter intensity was used to distinguish subpopulations based on cellular size and granularity, respectively. Our study revealed that prolonged pemetrexed pretreatment for 48 h prior to cisplatin significantly reduced long-term cell growth. Specifically, pretreatment for 48 h with pemetrexed induced a cell cycle arrest, mainly in the G2/M phase, accumulation of persistent DNA damage, and induction of a senescence phenotype. The present study demonstrates that optimizing the treatment schedule by pretreatment with pemetrexed increases the efficacy of the pemetrexed-cisplatin combination therapy in MPM. We show that the observed benefits are associated with the persistence of treatment-induced DNA damage. Our study suggests that an adjustment of the treatment schedule could improve the efficacy of the standard chemotherapy regimen for MPM and might improve patient outcomes