Predictors of nodal metastasising in laryngeal squamous cell carcinomas as decision support for neck dissection: comprehensive analysis of literature

BACKGROUND: A subset of advanced laryngeal squamous cell carcinomas (SCC) does not metastasize in regional lymph nodes (pN0). However, more than 30 % of tumors without signs of metastasizing in the clinical examination (cN0) show occult metastases. The guidelines of the German ENT-Society intend the extent of neck dissection (ND) depending on clinical stage of tumor and lymph nodes. If laryngeal surgery is followed by an adjuvant radiation/chemotherapy, ND is not always necessary. Histomorphological, immunohistochemical, or molecular parameters with predictive value for nodal metastasizing could support the planning for ND, especially in patients with cN0. METHODS: Within the last 20 years there were many publications concerning this problem. Herein, we analyzed the results of 455 publications. We have chosen studies regarding the predictive value of tumor stage, grading, peritumorous inflammation, invasion of lymphatic vessels, angioneogenesis, proliferation, overexpression of p53 or cyclin D1, inhibitors of cyclin-dependent kinases, growth factors, apoptosis, cell-adhesion, nm23, metalloproteinases, DNA/ploidy as well as tumor genetics. RESULTS: All examined parameters did not allow a fail-safe prediction of the risk for nodal metastasizing. CONCLUSIONS: Up to now, reliable predictors do not exist. The investigation of above mentioned parameters in pre-operative tumor biopsies is not helpful for the planning of ND in the stage cN0 (out of T1).     

Calcineurin inhibitor-free immunosuppression in kidney transplantation

The introduction of calcineurin inhibitors (CNI) revolutionized kidney transplantation (KTx). Exceptionally low acute rejection rates and excellent graft survival could be achieved with CNI-based (cyclosporine and tacrolimus) immunosuppressive protocols. However, despite short-term success, long-term graft attrition continues to be a significant problem, thus leaving clinicians looking for possible interventions. CNI nephrotoxicity is but one of numerous factors that may be contributing to long-term damage in transplant kidneys. Therefore, newer immunosuppressive agents such as mycophenolate mofetil and sirolimus (Rapa) have raised the possibility of withdrawing or avoiding CNIs altogether. Protocols exploring these options have gained greater attention over the last few years. Herein, we review studies addressing either CNI withdrawal or CNI avoidance strategies as well as discuss the risks versus benefits of these protocols. Given the accumulated experience to date, in our opinion, the use of CNIs as a part of immunosuppressive regimens remains the proven standard of care for renal transplant patients. The long-term safety and efficacy of CNI withdrawal and avoidance strategies need to be further validated in controlled clinical trials.     

Gastrointestinal side effects of mycophenolic acid in renal transplant patients: a reappraisal.

Patient and graft survival following renal transplantation have improved markedly over the past decade, meaning that physician attention has turned more towards minimizing short- and long-term toxicities associated with immunosuppressive regimens. Gastrointestinal (GI) adverse events are common following renal transplantation and all immunosuppressive regimens have been associated with such events. Mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) are potential components of immunosuppression regimens, and are associated with the most successful outcomes in kidney transplantation. The effects of MMF and EC-MPS are likely mediated via the active metabolite mycophenolic acid (MPA). The GI events caused by both MMF and EC-MPS may, in part, be related to MPA, independent of the formulation or route of administration. MPA may produce GI events either through direct action or through the action of it metabolites. However, many other factors may cause GI events observed following renal transplantation. These include the surgery itself and concurrent diseases such as diabetes, and bacterial, viral, fungal and parasitical infections. Additionally, numerous concomitant non-immunosuppressive agents, including antibiotics hypoglycaemic and proton-pump inhibitors, can be associated with GI events. In a recent trial in renal transplant patients with severe diarrhoea, approximately 50% of patients achieved resolution of diarrhoea through methods other than altering their immunosuppressive regimens. Indeed altering of the immunosuppressive regimen may lead to the risk of acute rejection. Thus, in order to reduce the risk of rejection and subsequent damage to the graft, it is important to consider other causes of GI events in renal transplant patients before altering immunosuppressive regimens.     

Liver metastases: incidence and histogenesis

Metastases are the most common malignant tumors of the liver. In the files of the Institute of Pathology of the University of Cologne 12,161 liver tissue cases are registered. Of them, 1,357 cases (11.2%) showed tumors or tumor like masses. Liver metastases of solid tumors were the largest group of the neoplasias with 611 cases (5.0%) followed by hepatocellular carcinoma (380 cases; 3.1%). Other entities were rare and include cholangiolar carcinoma (0.5%), vascular tumors (0.4%), lymphomas (0.4%), focal nodular hyperplasias (0.36%) and liver cell adenomas (0.23%). Adenocarcinomaa are the largest group of metastases with 400 cases (65.5%). 48.2% of this group were metastases of colorectal cancer, 13.5% of pancreatic cancer, 13% of breast cancer, 6.2% of gastric cancer, 4.5% of lung cancer and 3.7% of esophageal cancer. Neuroendocrine carcinomas are the second largest group with 16% of liver filiae. Other entities were rarely found. Metastases in cirrhotic livers are seldom. The gross findings, the histology, the differential diagnosis including immunohistochemistry and the value of the liver biopsy is discussed.