[Cough from the perspective of a gastroenterologist]. / Husten aus gastroenterologischer Sicht.

Cough from the perspective of a gastroenterologist Abstract. Chronic cough can have numerous origins. The work-up of these conditions should always include a multidisciplinary approach to exclude other causes first (cardial, pulmonary, structural changes of pharynx and larynx, allergies, malignancy) before thinking of an upper GI pathology. Cough as an extra-esophageal manifestation of gastroesophageal reflux disease (GERD) is the most common gastroenterological condition. From a gastroenterologist's perspective eosinophilic esophagitis (EoE) and esophageal motility disorders are potential differential diagnosis. If other worrisome symptoms (weight loss, anemia, dysphagia) are present at the same time an endoscopic evaluation with esophago-gastro-duodenoscopy (EGD) should be performed first to exclude a malignancy. Hereby one should perform biopsies of the esophagus to exclude an eosinophilic esophagitis (EoE). If the macroscopic and histopathology results of the EGD are unremarkable a probatory trial of acid-suppressive therapy with proton pump inhibitors (PPIs) is the first-line therapeutic option. For non-responders to PPI-therapy functional diagnostics are the next step. With the help of ambulatory pH-impedance monitoring one can diagnose a non- erosive reflux disease and an esophageal hypersensitivity. An esophageal manometry can deliver relevant information about the physiological anti-reflux barrier and diagnose motility disorders of the esophagus. Surgical therapy (antireflux surgery) can be an option for selected patients with proven reflux associated cough refractory to medical therapy. The aim of this review is to give an overview over a possible diagnostic-therapeutic algorithm from a gastroenterologist's point of view to approach the symptom cough.

Effects of definitive and salvage radiotherapy on the distribution of lymphocyte subpopulations in prostate cancer patients.

BACKGROUND: Radiotherapy (RT) is an established treatment for patients with primary and recurrent prostate cancer. Herein, the effects of definitive and salvage RT on the composition of lymphocyte subpopulations were investigated in patients with prostate cancer to study potential immune effects. PATIENTS AND METHODS: A total of 33 prostate cancer patients were treated with definitive (n = 10) or salvage RT (n = 23) after biochemical relapse. The absolute number of lymphocytes and the distribution of lymphocyte subpopulations were analyzed by multiparameter flow cytometry before RT, at the end of RT, and in the follow-up period. RESULTS: Absolute lymphocyte counts decreased significantly after RT in both patient groups and a significant drop was observed in the percentage of B cells directly after RT from 10.1 ± 1.3 to 6.0 ± 0.7% in patients with definitive RT and from 9.2 ± 0.8 to 5.8 ± 0.7% in patients with salvage RT. In contrast, the percentages of T and natural killer (NK) cells remained unaltered directly after RT in both patient groups. However, 1 year after RT, the percentage of CD3+ T cells was significantly lower in patients with definitive and salvage RT. The percentage of regulatory T cells was slightly upregulated in primary prostate cancer patients after definitive RT, but not after salvage RT. CONCLUSION: Definitive and salvage RT exert similar effects on the composition of lymphocyte subpopulations in prostate cancer patients. Total lymphocyte counts are lower in both patient groups compared to healthy controls and further decreased after RT. B cells are more sensitive to definitive and salvage RT than T and NK cells.

Comparative analysis of the effects of radiotherapy versus radiotherapy after adjuvant chemotherapy on the composition of lymphocyte subpopulations in breast cancer patients.

BACKGROUND: Breast cancer is the most common cancer in women worldwide and surgery, radiotherapy (RT) and chemotherapy (ChT) are frequently used to treat this cancer. Adjuvant RT has been shown to cause long-term changes in lymphocyte counts in the peripheral blood. Herein, the time course of changes in lymphocyte subpopulations upon RT was studied in patients with and without adjuvant ChT in order to explore its potential clinical impact. MATERIALS AND METHODS: Total lymphocyte counts and the composition of lymphocyte subpopulations before RT (t0), after 30 Gy (t1), at the end of RT (t2), and 6 weeks (t3), 6 months (t4), and 1 year (t5) after RT were studied by flow cytometry. RESULTS: Absolute lymphocyte counts were significantly lower in all breast cancer patients (n=40) before and also 1 year after RT compared to healthy controls. The percentage of CD3(+)/CD4(+) helper T cells and FoxP3(+) regulatory T cells increased significantly in patients without adjuvant ChT. Different NK cell subpopulations dropped during RT in patients with and without ChT, but recovered to initial levels 6months after RT (t4). During RT (t0-t2) the percentage of CD19(+) B cells significantly dropped in patients without ChT, but gradually increased in patients with adjuvant ChT. Both patient groups reached initial levels 6 months after RT (t4). CONCLUSION: Different lymphocyte subpopulations respond differently to RT with and without adjuvant ChT. CD4(+) T cells increase during RT, whereas NK cells and B cells decrease in patients without ChT, but recover within 6 months after RT. Treg cells gradually increase in patients without ChT from t0 to t5, but not in patients with adjuvant ChT.

Hsp70--a biomarker for tumor detection and monitoring of outcome of radiation therapy in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Tumor but not normal cells frequently overexpress heat shock protein 70 (Hsp70) and present it on their cell surface (mHsp70) from where it can be actively released. Therefore, membrane (mHsp70) and soluble Hsp70 (sHsp70) were investigated as potential tumor biomarkers and for monitoring the outcome of radiation therapy. METHODS: Biopsies and blood were collected from patients with squamous cell carcinoma of the head and neck (SCCHN) at different time points (before, during therapy and in the follow-up period). Hsp70 membrane expression was determined on single cell suspensions of tumor biopsies and reference tissues by flow cytometry, sHsp70 protein and antibody levels were determined in the serum of patients and healthy donors by ELISA and NK cell markers that are related to the presence of sHsp70 were analyzed in the patient's peripheral blood lymphocytes (PBL). RESULTS: Tumor biopsies exhibited significantly increased mHsp70 expression levels compared to the reference tissue. Soluble Hsp70 levels were significantly higher in SCCHN patients compared to healthy human volunteers and high mHsp70 expression levels on tumor cells were associated with high sHsp70 levels in the serum of patients. Following surgery and radiotherapy sHsp70 levels in patients dropped in patients without tumor relapse in the follow-up period. In contrast to sHsp70 protein, anti-Hsp70 antibody levels remained nearly unaltered in the serum of SCCHN patients before and after therapy. Furthermore, sHsp70 protein but not anti-Hsp70 antibody levels were found to be associated with the tumor volume in SCCHN patients before start of therapy. The expression densities of the activatory NK cell markers CD56, CD94, NKG2D, NKp30, Nkp44, and NKp46 differed in patients following therapeutic intervention. A significant increase in the density of NKG2D was observed in SCCHN patients in the follow-up period after surgery and radiotherapy. CONCLUSION: We suggest sHsp70 as a potential biomarker for detecting tumors and for monitoring the clinical outcome of radiotherapy in SCCHN patients.