BackgroundThere is a critical need for non-narcotic analgesic adjuncts in the treatment of thoracic pain. We evaluated the efficacy of intercostal cryoneurolysis as an analgesic adjunct for chest wall pain, specifically addressing the applicability of intercostal cryoneurolysis for pain control after chest wall trauma.MethodsA systematic review was performed through searches of PubMed, EMBASE, and the Cochrane Library. We included studies involving patients of all ages that evaluated the efficacy of intercostal cryoneurolysis as a pain adjunct for chest wall pathology. Quantitative and qualitative synthesis was performed.ResultsTwenty-three studies including 570 patients undergoing cryoneurolysis met eligibility criteria for quantitative analysis. Five subgroups of patients treated with intercostal cryoneurolysis were identified: pectus excavatum (nine studies); thoracotomy (eight studies); post-thoracotomy pain syndrome (three studies); malignant chest wall pain (two studies); and traumatic rib fractures (one study). There is overall low-quality evidence supporting intercostal cryoneurolysis as an analgesic adjunct for chest wall pain. A majority of studies demonstrated decreased inpatient narcotic use with intercostal cryoneurolysis compared with conventional pain modalities. Intercostal cryoneurolysis may also lead to decreased hospital length of stay. The procedure did not definitively increase operative time, and risk of complications was low.ConclusionsGiven the favorable risk-to-benefit profile, both percutaneous and thoracoscopic intercostal cryoneurolysis may serve as a worthwhile analgesic adjunct in trauma patients with rib fractures who have failed conventional medical management. However, further prospective studies are needed to improve quality of evidence.Level of evidenceLevel IV systematic reviews and meta-analyses.

Claudins, known as major contributors in the formation of the tight junction, are differentially expressed in malignant tumors as compared to the corresponding healthy tissues. Therefore, they are thought to play a role in carcinogenesis and tumor progression. Altered expression of claudin-1 has been reported in several tumor types including endometrial, papillary renal cell and colonic carcinoma, and increased claudin-1 mRNA levels have been observed in papillary thyroid carcinoma (PTC). In this study, we aimed at determining the pattern of claudin-1 expression in various types of thyroid lesions at the protein level and investigating the immunolocalization of beta-catenin reported to regulate claudin-1 expression. Samples included 19 PTCs, ten cases of corresponding regional lymph node metastasis, eight papillary microcarcinomas (PMC), 17 follicular thyroid carcinomas (FTC) and 19 follicular adenomas (FA). All cases were evaluated by quantitative immunohistochemistry. Conspicuous claudin-1 immunostaining was detected in the majority of PTC/PMC primary tumors and lymph node metastases (19/27 and 9/10, respectively). On the other hand, we found weak or no claudin-1 expression in any of the FA and FTC cases or peritumoral non-malignant thyroid tissues. Our data prove that high claudin-1 protein expression is specific for PTC and its regional lymph node metastases, while we failed to verify that claudin-1 is regulated by beta-catenin in thyroid tumors. Based on these results, claudin-1 may be a useful tumor marker for PTC.

Conjugation of gonadotropin-releasing hormone (GnRH) analogues GnRH-III, MI-1544, and MI-1892 through lysyl side chains and a tetrapeptide spacer, Gly-PheLeu-Gly (X) to a copolymer, poly(N-vinylpyrrolidone-comaleic acid) (P) caused increased antiproliferative activity toward MCF-7 and MDA-MB-231 breast, PC3 and LNCaP prostate, and Ishikawa endometrial cancer cell lines in culture and against tumor development by xenografts of the breast cancer cells in immunodeficient mice. MCF-7 cells treated with P-X-1544 and P-X-1892 displayed characteristic signs of apoptosis, including vacuoles in the cytoplasm, rounding up, apoptotic bodies, bleb formation, and DNA fragmentation. Conjugates, but not free peptides, inhibited cdc25 phosphatase and caused accumulation of Ishikawa and PC3 cells in the G 2 ͞M phase of the cell cycle after 24 h at lower doses and in the G 1 and G 2 phases after 48 h. Since P-X-peptides appear to be internalized, the increased cytotoxicity of the conjugates is attributed to protection of peptides from proteolysis, enhanced interaction of the peptides with the GnRH receptors, and͞or internalization of P-X-peptide receptor complexes so that P can exert toxic effects inside, possibly by inhibiting enzymes involved in the cell cycle. The additional specificity of P-X-peptides compared with free peptides for direct antiproliferative effects on the cancer cells but not for interactions in the pituitary indicates the therapeutic potential of the conjugates.