The extracellular matrix (ECM) is extensively remodeled in tumor tissues. Overproduction of collagens, pathological collagen crosslinking and alignment of fibers are major processes that ultimately result in an increased tissue stiffness. Although it is known that glycosaminoglycans (GAGs) play an important role in tumor signaling, their contribution to the biomechanical properties of tumor ECM is unknown. In this study, ECM structures of human colon carcinoma and normal (control) colon tissues were histologically identified. Using atomic force microscopy (AFM) nanoindentation, we show that the collagen-rich regions within the ECM of colon carcinoma tissues were significantly stiffer than the submucosal collagen-rich layer of control tissues. Screening of these regions with Raman microspectroscopy revealed significantly different molecular fingerprints for collagen fibers in colon carcinoma tissues compared to control tissues. We further showed an increased alignment of collagen fibers and elevated levels of GAG immuno-reactivity within the collagen network of colon carcinoma tissues. GAGs such as heparan sulfate and chondroitin sulfate were detected in significantly elevated levels in collagen fibers of carcinoma tissues. Moreover, immunodetection of the collagen-associated proteoglycan decorin was significantly decreased in carcinomas tissues of individual patients when compared with the corresponding control tissues. Overall a strong patient-to-patient variability was evident in the ECM composition, structure and biomechanics of individual colon carcinoma tissues. Although, biomechanical characteristics of tumor ECM were not directly impacted by GAG content, GAGs might play an important role during the mechanical and structural remodeling of pathological tumor ECM. To manipulate GAG expression and deposition in tumor microenvironments could represent a novel potential therapeutic strategy.

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HighlightsRare malignancy with poor prognosis.Survival only achieved in early stages with complete resection in combination with adjuvant therapy.Treatment analog to anaplastic thyroid cancer.

Appropriate pain therapy prior to diagnosis in patients with acute abdominal pain remains controversial. Several recent studies have demonstrated that pain therapy does not negatively influence either the diagnosis or subsequent treatment of these patients; however, current practice patterns continue to favour withholding pain medication prior to diagnosis and surgical treatment decision. Populations; and (6) Ethical and Medico-legal Considerations in Current Analgesia Practices. A comprehensive algorithm for analgesia for acute abdominal pain in the general adult population was developed. A review of the literature of common aetiologies and management of acute abdominal pain in the general adult population and special patient populations seen in the emergency room revealed that intravenous administration of paracetamol, dipyrone or piritramide are currently the analgesics of choice in this clinical setting. Combinations of non-opioids and opioids should be administered in patients with moderate, severe or extreme pain, adjusting the treatment on the basis of repeated pain assessment, which improves overall pain management.

Prolonged surgery time seems to correlate with initial postoperative hypocalcemia independently of the underlying disease and surgical expertise but does not affect the persistence of hypocalcemia. Initial symptomatic postoperative hypocalcemia after total thyroidectomy is associated with a high rate of persistent hypocalcemia.