Overview on the role of preoperative therapy in the management of kidney cancer.

The advent of molecular therapy through targeted kinase inhibitors (TKI) has revolutionized the management of renal cell carcinoma. Although surgical resection remains the cornerstone of any therapeutic plan, an increased risk of morbidity and mortality can be of concern in large and complex bulky tumors. Preoperative therapy with TKIs is hypothesized to facilitate resectability, reduce surgical morbidity and allow nephron-sparing surgery. Many concerns on the safety, efficacy and tolerability of these agents before surgery have halted the progress in this setting. In this paper, we will review the indications and safety of preoperative TKIs in RCC as well as the future approaches.

Residents' knowledge in transfusion medicine and educational programs: A pilot study.

BACKGROUND: Residents' knowledge in transfusion medicine significantly impacts the optimal use of blood and patient safety. Little is known regarding this topic in France in particular. The objectives were to evaluate their basic knowledge, to determine whether the objectives of the curricula were attained and subsequently to suggest ways for improvement. METHODS: A cross-sectional study was conducted on 50 first year medical and surgical specialty residents rotating in a French university hospital. RESULTS: Major gaps in the knowledge were noted among residents of various specialties, equally between those with low and sustained transfusion practice. The majority of these young doctors expressed difficulties in prescribing and handling transfusions, identifying and managing its complications and understanding their responsibilities. The roles of hemovigilance practitioners were further somehow unclear for participants. CONCLUSION: Given these results, action plans appear needed to limit consequences. A special transfusion medicine educational program should be added to the currently available medical education curriculum in order to ensure physicians have adequate knowledge of transfusion basics; at least a practical assisted situation during residency would be of valuable interest.

Blood donations mode: Assessment of the Lebanese model.

Voluntary non-remunerated donations remain the cornerstone for a safe and sustainable blood supply. According to the World Health Organization and other international scientific committees, all nations must switch their system of blood collection to voluntary non-remunerated donation. Several other types of blood donations still exist nowadays that will be discussed. Lebanon, similarly to other developing countries, is struggling to achieve 100% voluntary non-remunerated donations for the many existing social, demographic, cultural and economic problems. Replacement donations remain the predominant type, which creates huge burden on both hospital blood banks and patient families. Despite the limited resources, some improvements have been made recently in this field and Lebanon seems to be on the road of achieving 100% voluntary non-remunerated blood donation as requested by the World Health Organization. The Lebanese experience is worth sharing so that neighbouring countries facing similar problems could benefit from it.

Neoadjuvant isolated limb perfusion in newly diagnosed untreated patients with locally advanced soft tissue sarcomas of the extremities: the Gustave Roussy experience.

BACKGROUND: Limb-sparing surgery in locally advanced soft tissue sarcomas (LA STS) is challenging. The aim of this study is to evaluate upfront isolated limb perfusion (ILP) in untreated patients with LA STS. METHODS: All consecutive patients with LA STS of the limbs deemed borderline or unresectable and treated with upfront ILP as induction treatment between 2003 and 2016 were included. Demographic, clinical and long-term characteristics were obtained and retrospectively analyzed. RESULTS: 41 patients (pts), with a median age of 51 years [range 21-76], were identified (lower limb 68%, upper limb 32%). Liposarcoma and undifferentiated pleomorphic sarcoma were the most common subtypes (27% and 22%, respectively). Acute toxicities, using Wieberdink classification, were grade II (35 pts, 85%), grade III (2 pts, 5%) and no grade IV-V. Local control rate was 98%. 32 pts had limb-sparing surgery (78%). 1 pt had an early amputation due to progressive disease after ILP. 8 pts were not operated (four had RT alone, one had distant metastases, two had a complete response and one died 3 months after ILP of a pulmonary embolism). 36 pts (84%) received postoperative RT. After a median follow-up of 43 months, 18 pts (47%) relapsed. Median disease-free survival (DFS) was 6.7 years. The median overall survival (OS) was not reached. The 1-year, 5-year and 10-year DFS and OS rates were, respectively, 75%, 50% and 45%, and 90%, 63% and 55%. CONCLUSION: Upfront ILP is an efficient and well-tolerated limb-sparing procedure in borderline or unresectable LA STS without hampering OS.

Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder.

Metastatic urothelial carcinoma of the bladder is a rarely curable disease. Patients receive systemic therapy with limited response rates and survival benefits. The rescue regimens of these patients who have failed first-line treatment had remained problematic until the recent advances. Several trials with novel regimens, including immune checkpoint inhibitors and targeted therapy, to salvage relapsed urothelial carcinoma of the bladder have recently been published. However, the choice of an optimal treatment regimen remains challenging in the absence of randomized trials comparing regimen sequences. Daily clinical cases provoke the question of whether there is a preferred second-line regimen. This paper provides an overview of recent trials and proposes a management algorithm based on subgroup analyses and prognostic features.

Chemotherapy-induced differentiation to cure botryoid rhabdomyosarcoma: a case report and review of the literature.

Rhabdomyosarcoma (RMS) occurs rarely in adults and constitutes 2-6% of all uterine neoplasms. The authors report the case of a 26-year-old woman diagnosed with botryoid RMS that presented discordant progression results on follow up imaging and cytodifferentiation on pathologic control. This case showed that radiological evaluation could be misleading as the tumor demonstrated chemotherapy-induced differentiation without volume reduction. This case illustrates the limitations of using the imaging anatomical dimensions of sarcomas for treatment planning and highlights the potential role of functional imaging to assess the response to treatment.

Estrogens control inflammation in experimental colitis.

There is now a wealth of experimental evidence indicating that the deficit in endogenous estrogen facilitates the onset of inflammation that can be antagonized by estrogen replacement therapy. This work investigated the role of estrogen in the control of intestinal inflammation in a panel of colitis models, focusing on the morphological changes, the activity of mast cells, the expression of cytokines (IL-1beta, IL-6, and TNF-alpha), fibronectin and reactive oxygen species. Two hundred adult male rats were divided into 4 groups: colitis was induced in Group I and Group II but only the latter was treated with estrogen; Group III received estrogen only, and Group IV saline. Colitis was induced in 4 models using: iodoacetamide; iodoacetamide + enteropathogenic E. coli; 2, 4, 6-Trinitrobenzene sulfonic acid; and dextran sulfate sodium salt. Macroscopic and microscopic evaluations of abdominal structures as well as molecular analysis were made on days 7, 14, 28 and 56. There was a significant improvement in the health condition of the estrogen-treated rats: the inflammation scores were reduced by at least 10-15%, the number of mast cells in the colon decreased by 30%, fibronectin expression was only 50% and reactive oxygen species decreased by 30%. In addition, there was a significant decrease in TNF-alpha, IL-6 and IL-1beta expression by about 25%. In conclusion, there was an improvement in the inflammatory status in all estrogen-treated groups through the duration of the experiment at all-time points. In addition, there was less tissue necrosis as depicted by less fibronectin and a marked antioxidant effect.

Modulation of Beta2 and Beta3 integrins in experimental colitis induced by iodoacetamide and enteropathogenic E. coli.

Integrins can modulate the infiltration of inflammatory cells and the secretion of various inflammatory mediators, essential players in the pathogenesis of colitis. This study explores the role of beta2 and beta3 integrin signaling and their possible role in experimental colitis. A total of 160 adult male Sprague-Dawly rats were divided into 4 equal groups: methylcellulose, bacteria, iodoacetamide and iodoacetamide plus bacteria. Clinical symptoms and signs of colitis were checked daily and colonic tissues were biopsied on days 3, 14, 28, and 56 post induction. Histological studies along with histochemical analysis and polymerase chain reaction of beta2, beta3 and alphavbeta3 were performed according to standard procedures. The symptoms and signs were consistent with previously reported data on active colitis. The highest expression of beta3 integrin was in the combined treatment mostly on platelets, endothelial and inflammatory cells. In the same group, the expression of alphavbeta3 integrin complex reached the highest score after 56 days in all colonic layers. Beta2 integrin expression showed a 3-4-fold increase in the combined treatment group at all time points and kept increasing till day 56. It was mostly expressed in the mucosa and submucosa. In addition, the expression of both αvβ3 and αiiβ3 integrins was also elevated 2- to 10-fold, respectively, in the same colitis groups throughout the duration of the experiment. In conclusion, the combined treatment of IA and Enteropathogenic E. coli led to a significant upregulation of all the tested integrins throughout the experimental duration. Such upregulation of integrins could have contributed to the increase and chronicity of inflammation.

Effect of autologous platelet-rich plasma on distraction osteogenesis in the mandible of rabbits: a morphologic and morphometric approach.

Distraction osteogenesis of the jaw is a common surgical practice in the treatment of pediatric craniofacial deformities. Autologous platelet rich plasma (PRP) has been used to increase the healing potential of bones in humans during distraction osteogenesis. This article aims to study the morphometric and morphologic parameters resulting from the effect of PRP on bone healing after mandibular distraction in rabbits. Right mandibular distraction was performed in 12 rabbits divided equally into 2 groups. PRP and physiological saline were injected, according to a defined protocol, in the callus following distraction of the experimental and control groups respectively. The rabbits were sacrificed after a consolidation period of 45 days and the mandibles were surgically removed. Bone mineral density, radiographic analysis, mechanical properties and histological features of the lengthened bones were assessed using radiographic examination, dual X-ray absorptiometry, biomechanical testing and histology. Results showed that the regenerate bone density, the amount of trabeculation in addition to the bone mineral density and mineral content, as measured by absorptiometry, were better with PRP but not significantly different between groups. Two radiographs revealed a more consistent healing in the experimental mandibles compared with erratic outcomes in corresponding controls. Two of the latter could not be subjected to any mechanical testing because the mandibular parts, connected with fibrous tissue, were separated. Consequently, the biomechanical test depicted greater maximal loads in the experimental group. The histological studies exhibited more ossification and less connective tissue fibers in the experimental group. PRP accelerated healing of mandibles in rabbits following distraction and improved their biomechanical properties. These findings have significant clinical implications on reducing the period of consolidation of the mandibles which may not be immobilized like other bones for long periods of time.