Antitumorigenic action of nelfinavir: Effects on multiple myeloma and hematologic malignancies (Review).

Protease inhibitors (PIs) inhibit HIV­1 and HIV­2 proteases, impeding virus replication and liberation of viral elements from infected cells. In human immunodeficiency virus (HIV) subjects receiving PI­based treatment, an impressive decrease in the amount of HIV­associated cancers, unconnected to viral burden or CD4 amount was observed. Research has reported that PIs have influence on cancer proliferation, spread, and survival as an effect on endoplasmic reticulum stress, proteasome, NF­κB and Akt signalling. Nelfinavir (NFV) is a nonpeptidic PI that functions by connecting to the catalytic site of the HIV protease, thus stopping the cleavage of viral polyprotein into complete, operative proteins that are fundamental for viral survival. NFV, currently not frequently employed for antiretroviral treatment, has demonstrated noteworthy off target effects in tumor patients with or without HIV disease. NFV appears to cause cell death in tumor cells by different mechanisms, which include necrosis, apoptosis and autophagy. In this review, data from preclinical research and clinical trials are reported and the mechanisms of action of NFV and their results in the treatment of hematologic malignancies, such as acute myeloid leukemia, chronic lymphoid leukemia, and diffuse large B cell lymphoma, and especially in patients with multiple myeloma are examined. In the future, experimental studies may help identify the role of NFV in cancer treatment and may promote the application of this drug into daily clinical practice.

Role of the microbiota in hematologic malignancies.

Human beings are inhabited by innumerable microorganisms that interrelate with the host in a reciprocal way, establishing a combined and efficient ecosystem - the microbiota - that can affect healthiness as well as disease. There is evidence that the conformation of the microbiota may influence, and is controlled by, the human immune system. Microbes existing in human tissues offer a multiplicity of advantages that participate in functional actions in the host through the adjustment of essential processes such as immunity, signal transduction, and metabolism. The imbalance of this microbial structure has been connected with the pathogenesis and progression of cancer. We reviewed the present knowledge of the diverse microbial ecosystems and we investigated their potential link to carcinogenesis, and the possibility of using advantageous microbes in controlling and preventing hematologic malignancies.

Standardisation of minimal residual disease in multiple myeloma.

The assessment of the effectiveness of chemotherapy in oncology cannot disregard the concept of minimal residual disease (MRD). In fact, the efforts of numerous scientific groups all over the world are currently focusing on this issue, with the sole purpose of defining sensitive, effective assessment criteria that are, above all, able to give acceptable, easily repeatable results worldwide. Regarding this issue, especially with the advent of new drugs, multiple myeloma is one of the haematologic malignancies for which a consensus has not yet been reached. In this review, we analyse various techniques that have been used to improve the sensitivity of response, aimed at reducing the cut-off values previously allowed, as well as serological values like serum-free light chain, or immunophenotypic tools on bone marrow or peripheral blood, like multi-parameter flow cytometry, or molecular ones such as allele-specific oligonucleotide (ASO)-qPCR and next-generation/high-throughput sequencing technologies (NGS). Moreover, our discussion makes a brief reference to promising techniques, such as mass spectrometry for identifying Ig light chain (LC) in peripheral blood, and the assessment of gene expression profile not only in defining prognostic risk at the diagnosis but also as a tool for evaluation of response.

Vaccination strategies in lymphoproliferative disorders: Failures and successes.

Anti-tumor vaccines in lymphoproliferative disorders hold out the prospect of effective tumor therapies with minimal side effects. The addition of immunotherapy to old and new chemotherapy regimens has improved both response rates and disease-free survival, leading in many cases to an extended overall survival. Ideally, an antigen that is used for vaccination would be specifically expressed in the tumor; it must have an important, causal part in the multifactorial process that leads to cancer, and it must be expressed stably even after it is attacked by the immune system. Immunotherapies, which aim to activate the immune system to kill cancer cells, include strategies to increase the frequency or potency of antitumor T cells, to overcome suppressive factors in the tumor microenvironment, and to reduce T-cell suppression systemically. In this review, we focus on the results of clinical trials of vaccination in lymphoma, and discuss potential strategies to enhance the efficacy of immunotherapy in the future.

Which length for the revision stem?

The results of 79 stem implantations performed between 1981 and 1992 are presented. Mean clinical and radiographic follow-up was obtained 36 months after surgery. All of the prostheses were substituted due to aseptic loosening: of these 68% were cemented. Femoral osteolytic lesions secondary to loosening was classified based on the Paprosky protocol. A severe femoral osteolytic defect (type 2b, 2c or 3 according to Paprosky) was associated with 4% of the cases of loosened cementless prostheses, and with 37% of the cemented ones. Homoplastic bone grafts were used in 40% of the patients. The length of the stems used for reimplantation was short (12-13 cm) in 43%, standard (17-18 cm) in 49%, and long (> or = 22 cm) in 7% of the cases. These stems were cemented in 32% of the cases. The incidence of cementation was different in relation to length, as 62.5% of the short stems were cemented, as compared to 5.3% of the stems of standard length. Clinical results were excellent in 90% of the cases submitted to surgery with short stems, in 80% of those treated with standard stems, and in 50% of the cases of revision surgery where long stems were used. Radiographically, 97% of the short stems were osteointegrated, as compared to 94% of the standard stems and to 25% of the long ones, which were only used in a very few cases to be considered quite complex ones.

Femoral bone remodeling: clinical experience with cemented and cementless total hip arthroplasty.

A radiographic study of femoral bone tissue remodeling around hip arthroplasty was carried out simultaneously in two series totalling 224 cementless and 77 cemented prostheses. Remodeling was analyzed by detailed visual evaluation of the radiographic assessment. The results show that the phenomenon of bone remodeling is still evolving more than 5 years after surgery. Bone demineralization of the proximal femur is more evident in cementless prostheses than in those stabilized with acrylic cement (24% vs. 12%). The preoperative state of mineralization significantly influences bone remodeling.

Supracondylar process of the humerus: four cases.

Four cases of supracondylar process of the humerus are presented. Two of the patients were asymptomatic and in one of these the supracondylar process was fractured. In a third there was median nerve compression and in the last there was ulnar nerve entrapment. The anatomical features, clinical symptoms and therapy are described. Good results were obtained after resection of the supracondylar process; neurological symptoms regressed one month after surgery.

Dysplasia epiphysealis hemimelica. (A review of 19 cases).

Nineteen cases of dysplasia epiphysealis hemimelica are presented. Eleven were single and 8 were multiple. The writers illustrate the clinical and radiographic aspects of this condition, and stress the importance of surgical treatment as soon as the first clinical symptoms appear.

The treatment of pulmonary metastases in osteosarcoma. Preliminary observations on 30 cases.

Thirty cases of pulmonary metastases in osteosarcoma are analysed from the point of view of evaluating the indications for localised excision, and also to report the results obtained. This group is compared with 42 analogous cases in which the metastases were not treated surgically. The results of pulmonary surgery is shown to be effective in the multidisciplinary treatment of osteosarcoma with pulmonary metastases.

Pigmented villonodular synovitis of the hip. Study of 9 cases.

Pigmented villonodular synovitis of the hip is a very rare condition. The authors report 9 cases out of a total of 139 cases of pigmented villonodular synovitis of joints observed at the Rizzoli Institute in the last 35 years. They describe the clinical, radiological and pathological aspects, and discuss the problems of differential diagnosis. In particular, they discuss the indications for surgery (total synovectomy or arthroprosthesis) and the post-operative regime.

Mesenchymal chondrosarcoma of bone and soft tissues.

Mesenchymal chondrosarcoma of bone and soft tissues treated at the Istituto Ortopedico Rizzoli are reviewed. The skeletal locations were prominent in five cases. Only two cases were in the soft tissues. Radiographic picture in the bone shows an aggressive osteolysis, with soft tissues invasion. Histologic picture is the same in bone and soft tissues, and is highly distinctive: islands of well-differentiated chondrosarcoma embedded in undifferentiated mesenchymal cells with high malignancy characteristics. The cases showed a poor prognosis, and no patient survived more than four years.

Maffucci's syndrome. Report of 3 cases and review of the literature.

Maffucci's syndrome is a rare condition which is not hereditary. It is manifested by multiple chondromata associated with subcutaneous angiomata. Up to now only 109 cases have been reported in the literature. Malignant degeneration is reported in about 15% of cases. The authors present 3 more cases, in one of which sarcomatous degeneration occurred in one of the chondromata.

The surgical treatment of bone metastases.

The Authors consider the surgical treatment of 122 patients (125 operations) with metastatic lesions of the skeleton. They outline the most commonly used surgical techniques (arthro- and endoprostheses, endomedullary implants, plates). Operations need to be planned with special standards and methods since the bone tissue is undergoing serious structural changes and the patients need rapid rehabilitation. To this end, the utility is emphasized of the substitution with prostheses even of extensive skeletal segments and the use of acrylic cement is recommended to replace loss of substance caused by neoplastic osteolysis. The results obtained are classified as good, fair and bad according to the degree of solidity of the synthesis obtained, disappearance or relief of pain and recovery of function. The complications are discussed and the incidence of survival.

Transolecranal dislocations.

The authors report the results obtained in the treatment of twenty-four cases of transolecranal dislocation (anterior dislocation of the elbow accompanied by fracture of the olecranon). Follow up examinations were performed after one to eight years. Discussion of the types of dislocation is followed by a description of the operations necessary to reduce and stabilise the individual lesions. In the light of the results obtained the authors still consider it advisable for the elbow to be immobilised in plaster for three weeks to allow the capsulo-ligamentous lesions caused by the dislocation to cicatrize.