Hypoxia-Associated Marker CA IX Does Not Predict the Response of Locally Advanced Rectal Cancers to Neoadjuvant Chemoradiotherapy.

Hypoxia-associated proteome changes have been shown to be associated with resistance to chemo- and radiotherapy. Our study evaluated the role of the hypoxia-inducible (HIF)-1 target gene carbonic anhydrase (CA) IX in the prediction of the response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer (stages II and III). A total of 29 pretreatment biopsy specimens were stained for CA IX by immunohistochemistry, converted to digital images and evaluated in a quantitative fashion using image analysis software. Contrary to our expectations, a trend towards a correlation between better tumor regression (>50%) and higher expression of CA IX (p=0.056) was found. CA IX was also present more frequently in pathological tumor stage T1 (pT1) tumors (p=0.048). Conversely, no association with lymph node metastasis was identified. In conclusion, as a single marker, CA IX expression is not able to identify a hypoxia-related treatment resistant phenotype in rectal cancer.

Achalasia with megaesophagus and tracheal compression in a young patient: A case report.

INTRODUCTION: Achalasia is one of the most common causes of dysphagia. Typical symptoms include difficulties in controlling the swallowing process, regurgitation, weight loss, and chest pain. A megaesophagus rarely causes tracheal compression with consecutive acute dyspnea or similar respiratory symptoms. PRESENTATION OF CASE: A 23-year-old male patient presented with difficulties in swallowing, a consecutive massive weight loss over the past three years, and minor respiratory ailments. Further diagnostics revealed a megaesophagus caused by achalasia leading to a severe compression of the trachea. A laparoscopic Heller myotomy with anterior semi-fundoplication 180° according to Dor was performed. DISCUSSION: Acute dyspnea and similar respiratory symptoms are rarely observed in patients with achalasia, especially in young patients. Early diagnosis and timely, proper treatment are the hallmarks of restoring esophageal and tracheobronchial function and of successful prevention of severe long-lasting complications of the disease. When not treated properly, the disease may have progressed rapidly, leading to distinct respiratory symptoms such as stridor and acute dyspnea CONCLUSION: This report emphasizes that physicians should be alert and consider airway obstruction and signs of dyspnea as severe and threatening symptoms in extensive cases of achalasia with megaesophagus. Early surgical treatment provides a therapeutic option to obviate the occurrence of acute respiratory distress and consecutive complications. In particular, difficulties in intubation prior to surgery must be considered.

Late consequences of traumatic rupture of the diaphragm.

A 54-year-old man was admitted to our clinic due to elevated γ-glutamyltransferase, without any clinical symptoms. About 25 years ago, he had undergone blunt abdominal and thoracic trauma during an accident. No diagnostic measures or therapy had been performed at that time. Serum bilirubin was normal, but the values for alanine transaminase, aspartate transaminase, and alkaline phosphatase were slightly above the reference range. Sonography of the abdomen revealed dilated intrahepatic bile ducts up to 3 mm in diameter and steatosis of the liver grade I. CT scan and MRI of the thorax and abdomen showed a giant hiatal hernia with transposition of upper abdominal organs into the chest. As the patient presented clinically completely asymptomatic, without dyspnea, dysfunction of phonation or ingestion, we decided a conservative treatment with Ursodesoxycholic acid. The liver values resolved with this regimen gradually. At follow-up examination 1 year later, they had normalized. Spirometry showed a reduced lung capacity (3.44 L; 64.4% of the desired value) and a reduced FEV1 (forced expiratory volume in one second) of 2.84 L (70.2% of the desired value). Further diagnostics revealed normal otorhinolaryngological and phoniatric findings including stroboscopy of the vocal folds and voice range profile.

Rectal Cancer: MR imaging of the mesorectal fascia and effect of chemoradiation on assessment of tumor involvement.

PURPOSE: To evaluate the impact of chemoradiation on the reliability of MRI in assessing tumor involvement of the mesorectal fascia in patients with rectal cancer. MATERIALS AND METHODS: Presurgical MRI was performed in 150 patients; among them 85 had received neoadjuvant long-course chemoradiation. A standardized imaging protocol (1.5 Tesla [T] system, image voxel size 0.6 × 0.4 × 3 mm(3) ), standardized surgery, and histopathological examination were applied for the entire patient population. Images were analyzed to identify potential tumor involvement of the mesorectal fascia (minimum tumor distance to fascia ≤1 mm) and compared with histopathology as the reference standard. Results of nonirradiated and irradiated patients were compared to define the impact of chemoradiation on imaging reliability. RESULTS: In nonirradiated patients, MRI was reliable in predicting or excluding tumor involvement of the mesorectal fascia, positive predictive value 80%, negative predictive value 89%. The frequency of overestimating tumor involvement was significantly higher in irradiated patients (P = 0.005, positive predictive value 42%). CONCLUSION: Discussions about MRI assessment of tumor involvement of the mesorectal fascia as a basis for recommending neoadjuvant chemoradiation should focus on investigations that excluded irradiated patients, because MRI is less reliable after chemoradiation and tends to overestimate mesorectal tumor involvement.

A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells.

BACKGROUND: The protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target, DNA double-strand break (DSB) formation and rejoining, apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2. METHODS: MRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB), or mock-treated, 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis (PFGE) as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry, survival was quantified by clonogenic assay. RESULTS: TBB treatment did not affect initial DNA fragmention (PFGE; up to 80 Gy) or foci formation (1 Gy). While DNA fragment rejoining (PFGE) was not inhibited by the drug, TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions (monotherapies or combination), but TBB treatment at this moderately toxic concentration of 20 µM (about 40% survival) enhanced radiation-induced cell killing in the clonogenic assay. CONCLUSIONS: The data imply a role of CK2 in gamma-H2AX dephosporylation, most likely through its known ability to stimulate PP2A phosphatase, rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from interference with an apoptosis suppression function of CK2 in these cells but could reflect inhibitor-induced uncoupling of DNA damage response decay from break ligation.