Targeted therapy in BRAF mutated aggressive papillary craniopharyngioma: a case report and overview of the literature.

BACKGROUND: Papillary craniopharyngiomas harbor the BRAF V600E mutation, which paves the way for using BRAF inhibitor molecules to treat tumors refractory to standard therapies. Single case reports confirmed the efficacy of targeted therapy. However, most reports were limited by the short follow-up. We describe the long-term course of a patient treated with dual-agent BRAF and MEK inhibitors and review the available literature. CASE REPORT: A 75-year-old male patient had recurrence of a papillary craniopharyngioma after transsphenoidal surgery and Gamma Knife radiosurgery. Review of the pathologic specimen confirmed the presence of the BRAF V600E mutation. Because of the few therapeutic options, we decided to initiate BRAF/MEK inhibitor combined therapy for six months. Rapid reduction of the tumor occurred, but three months after quitting combined medical therapy the tumor recurred. BRAF/MEK inhibitor therapy was resumed and the tumor again showed a marked reduction. The second course was maintained for 20 months and the tumor showed another recurrence within three months, which, again, responded to a third course of targeted therapy. CONCLUSIONS: Our study confirms the excellent response of papillary craniopharyngioma to combined BRAF and MEK inhibitors. However, rapid tumor recurrence is the rule when medical therapy is stopped. Resistance to a second and third course of targeted therapy did not occur, suggesting that tumor mutations affecting the response to drugs seems an uncommon event in papillary craniopharyngioma. The exact role of targeted therapy in the treatment algorithm of papillary craniopharyngiomas has still to be refined.

Early regression index (ERI) on MR images as response predictor in esophageal cancer treated with neoadjuvant chemo-radiotherapy: Interim analysis of the prospective ESCAPE trial.

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Metastatic incidence of (PET)CT positive lung hilar and retroperitoneal lymph nodes in esophageal cancer patients.

BACKGROUND: Extra-regional lymph node metastases strongly determine treatment options in patients with esophageal cancer. Staging modalities such as (FDG-PET) CT scanning frequently show activity in retroperitoneal and lung hilar lymph nodes. This study evaluated the incidence of histologically confirmed metastases, treatment approach and recurrence patterns in patients with (FDG-PET) CT positivity in these regions. METHODS: All patients with (FDG-PET-) CT positive hilar and/or retroperitoneal lymph nodes at primary staging or restaging discussed at a multidisciplinary tumor board meeting for staging of esophageal cancer between January 2012-December 2017 were included. Biopsies and follow-up were evaluated to determine the presence of metastases and progression rates. RESULTS: From 2012 to 2017, 65 of 857 patients (7.6%) were selected with positive retroperitoneal and/or hilar lymph nodes. A total of 47/65 (72.3%) patients had positive retroperitoneal lymph nodes, which contained metastases in 19 (29.2%). When no biopsy was performed and curative treatment was given (n = 14), 9 patients had progression or locoregional and distant recurrence. Positive hilar lymph nodes were identified in 21 (32.3%) patients; 4 were biopsied and none contained metastases. In these patients no recurrence of disease was seen during follow-up. CONCLUSIONS: The majority of biopsied (PET)CT-positive retroperitoneal lymph nodes at staging contained metastases, while biopsied (PET)CT-positive hilar nodes did not. Histological evaluation of (PET)CT -positive retroperitoneal lymph nodes at staging imaging is recommended, while based on this small series, (PET)CT-positive hilar lymph nodes most likely represent reactive lymphadenopathy.

Experimental and Numerical Characterization of the Mechanical Masseter Muscle Response During Biting.

Predictive simulations of the mastication system would significantly improve our understanding of temporomandibular joint (TMJ) disorders and the planning of cranio-maxillofacial surgery procedures. Respective computational models must be validated by experimental data from in vivo characterization of the mastication system's mechanical response. The present pilot-study demonstrates the feasibility of a combined experimental and numerical procedure to validate a computer model of the masseter muscle. An experimental setup is proposed that provides a simultaneous bite force measurement and ultrasound-based visualization of muscle deformation. The direct comparison of the experimentally observed and numerically predicted muscle response demonstrates the predictive capabilities of such anatomically accurate biting models. Differences between molar and incisor biting are investigated; muscle deformation is recorded for three different bite forces in order to capture the effect of increasing muscle fiber recruitment. The three-dimensional (3D) muscle deformation at each bite position and force-level is approximatively reconstructed from ultrasound measurements in five distinct cross-sectional areas (four horizontal and one vertical cross section). The experimental work is accompanied by numerical simulations to validate the predictive capabilities of a constitutive muscle model previously formulated. An anatomy-based, fully 3D model of the masseter muscle is created from magnetic resonance images (MRI) of the same subject. The direct comparison of experimental and numerical results revealed good agreement for maximum bite forces and masseter deformations in both biting positions. The present work therefore presents a feasible in vivo measurement system to validate numerically predicted masseter muscle contractions during mastication.

Radiofrequency versus microwave ablation for treatment of the lung tumours: LUMIRA (lung microwave radiofrequency) randomized trial.

The LUMIRA trial evaluated the effectiveness of radiofrequency (RFA) and microwave ablation (MWA) in lung tumours ablation and defining more precisely their fields of application. It is a controlled prospective multi-centre random trial with 1:1 randomization. Fifty-two patients in stage IV disease (15 females and 37 males, mean age 69 y.o., range 40-87) were included. We randomized the patients in two different subgroups: MWA group and RFA group. For each group, we evaluated the technical and clinical success, the overall survival and complication rate. Inter-group difference was compared using Chi-square test or Fisher's exact test for categorical variables and one-way ANOVA test for continuous variables. For RFA group, there was a significant reduction in tumour size only between 6 and 12 months (p value = 0.0014). For MWA group, there was a significant reduction in tumour size between 6 and 12 months (p value = 0.0003) and between pre-therapy and 12 months (p value = 0.0215). There were not significant differences between the two groups in terms of survival time (p value = 0.883), while the pain level in MWA group was significantly less than in RFA group (1.79 < 3.25, p value = 0.0043). In conclusion, our trial confirms RFA and MWA are both excellent choices in terms of efficacy and safety in lung tumour treatments. However, when compared to RFA therapy, MWA produced a less intraprocedural pain and a significant reduction in tumour mass.

Simultaneous Liver-Kidney Transplantation in Adults: A Single-center Experience Comparing Results With Isolated Liver Transplantation.

BACKGROUND: After introduction of the Model for End-Stage Liver Disease (MELD) score in 2002, a worldwide increasing number of simultaneous liver-kidney transplantations (SLKTx) has been observed. However, organ shortage puts into question the allocation of 2 grafts to 1 recipient. This retrospective, single-center study compared SLKTx results with isolated liver transplantation (LTx). METHODS: Between 1995 and 2013, 37 SLKTx were performed in adult recipients. Every SLKTx was matched by donor age (±5 years) and transplantation date with 2 LTx (n = 74). Pretransplant, intraoperative, and post-transplant variables were collected; liver graft and patient survivals were calculated. RESULTS: As expected, donor age was similar in the 2 groups (median, 39.7 years), whereas serum creatinine level, glomerular filtration rate, and MELD and D-MELD (donor age*MELD) scores were significantly higher in the SLKTx group. SLKTx had longer waiting list time (P = .0034) as well as higher surgical difficulty, testified by more blood transfusions (P = .0083), increased use of classic caval reconstruction (P = .0024), and more frequent need of abdominal packing for bleeding control (P = .0003). In addition, duration of hospital stay (P < .0001), second-look surgery (P = .0082), post-transplant dialysis (P < .0001), and post-transplant infections (P = .04) were significantly greater in SLKTx group. Acute rejection episodes involving the liver were significantly less in SLKTx than in LTx (14% vs 41%; P = .0045). Liver graft and patient survival at 10 years after transplantation was similar in the 2 groups (liver graft: SLKTx, 80% vs LTx, 77% [P = .85]; patient: SLKTx, 86% vs LTx, 79% [P = .56]). CONCLUSIONS: Despite being technically challenging, SLKTx provided excellent long-term results and was shown to be an effective use of liver grafts.

Challenging the in-vivo assessment of biomechanical properties of the uterine cervix: A critical analysis of ultrasound based quasi-static procedures.

Measuring the stiffness of the uterine cervix might be useful in the prediction of preterm delivery, a still unsolved health issue of global dimensions. Recently, a number of clinical studies have addressed this topic, proposing quantitative methods for the assessment of the mechanical properties of the cervix. Quasi-static elastography, maximum compressibility using ultrasound and aspiration tests have been applied for this purpose. The results obtained with the different methods seem to provide contradictory information about the physiologic development of cervical stiffness during pregnancy. Simulations and experiments were performed in order to rationalize the findings obtained with ultrasound based, quasi-static procedures. The experimental and computational results clearly illustrate that standardization of quasi-static elastography leads to repeatable strain values, but for different loading forces. Since force cannot be controlled, this current approach does not allow the distinction between a globally soft and stiff cervix. It is further shown that introducing a reference elastomer into the elastography measurement might overcome the problem of force standardization, but a careful mechanical analysis is required to obtain reliable stiffness values for cervical tissue. In contrast, the maximum compressibility procedure leads to a repeatable, semi-quantitative assessment of cervical consistency, due to the nonlinear nature of the mechanical behavior of cervical tissue. The evolution of cervical stiffness in pregnancy obtained with this procedure is in line with data from aspiration tests.

Validation of the Non-Union Scoring System in 300 long bone non-unions.

INTRODUCTION: Non-union of long bones is a significant consequence of fracture treatment. The ideal classification for non-union of long bones would give sufficient significant information to the orthopaedic surgeon to enable good management of the treatment required and to facilitate the creation of comparable study groups for research purposes. The Non-Union Scoring System (NUSS) is a new scoring system to assist surgeons in the choice of the correct treatment in non-union surgery. The aim of this study was to determine the evidence supporting the use of the NUSS classification in the treatment of non-unions of long bones and to validate the treatment algorithm suggested by this scoring system. MATERIALS AND METHODS: A total of 300 patients with non-union of the long bones were included in the clinical study. RESULTS: A radiographic and clinical healing was reached in 60 of 69 non-unions (86%) in group 1 (0-25 points), in 102 of 117 non-unions (87%) in group 2 (26-50 points), and in 69 of 84 (82%) in group 3 (51-75 points). The mean time to clinical healing was 7.17 ± 1.85 months in group 1, 7.30 ± 1.72 months in group 2 and 7.60 ± 1.49 months in group 3. The mean time to radiographic healing was 8.78 ± 2.04 months in group 1, 9.02 ± 1.84 months in group 2 and 9.53 ± 1.40 months in group 3. DISCUSSION: There are few articles in the scientific literature that examine the classification systems for non-union. CONCLUSIONS: A statistical analysis of the first results we have obtained with the use of NUSS showed significant rates of union in all the evaluated groups. This indicates that NUSS could be an appropriate scoring system to classify and stratify non-unions and to enable the surgeon to choose the correct treatment.

Megaprosthesis in post-traumatic and periprosthetic large bone defects: Issues to consider.

INTRODUCTION: The recent evolution of prosthesis technology has enabled the surgeon to replace entire limbs. These special prostheses, or megaprostheses, were developed for the treatment of severe oncological bone loss; however, the indications and applications of these devices have expanded to other orthopaedic and trauma situations. For some years, surgeons have been implanting megaprostheses in non-oncological conditions, such as acute trauma in severe bone loss and poor bone quality; post-traumatic failures, both aseptic and septic (represented by complex non-unions and critical size bone defects); major bone loss in prosthetic revision, both aseptic and septic; periprosthetic fractures with component mobilisation and poor bone stock condition. The purpose of this study was to evaluate retrospectively the complications during and after the implantation of megaprosthesis of the lower limb in post-traumatic and prosthetic bone loss, and to propose tips about how to avoid and manage such complications. MATERIALS AND METHODS: All the complications and difficulties we have encountered during or after the implantation of megaprosthesis in non-oncology patients were evaluated retrospectively. A total of 72 patients were treated with large resection mono-and bi-articular prostheses between January 2008 and January 2014. RESULTS: The main critical problems found in the study were: restoration of the correct length and rotation of the limb; reconstruction of the knee extensor mechanism; trochanteric reconstruction; stability/dislocation of the implant; mobility/range of motion (ROM) of the implant; skin cover; sepsis, and bone quality. CONCLUSION: Megaprosthesis in severe bone loss can be considered as an available solution for the orthopaedic surgeon in extreme, appropriately selected cases. This type of complex surgery must be performed in specialised centres where knowledge and technologies are present. Patients with severe bone loss should not be treated in the same way as oncology patients because life expectancy is definitely longer; therefore, the surgical technique and the system implantation must be extremely rigorous to ensure longevity of the prosthesis. The characteristics of the bone and soft tissue conditions in these patients are very different from those presented by oncology patients, which creates critical problems that the surgeon should be able to manage to avoid serious complications.

Treatment of AVN using the induction chamber technique and a biological-based approach: indications and clinical results.

OBJECTIVE: To determine the efficacy of core decompression (CD) technique combined with recombinant morphogenetic proteins, autologous mesenchymal stem cells (MSCs) and xenograft bone substitute into the necrotic lesion of the femoral head on clinical symptoms and on the progression of osteonecrosis of the femoral head. PATIENTS AND METHODS: A total of 38 patients (40 hips) with early stage osteonecrosis of the femoral head were studied over a 4-year period. RESULTS: CD technique combined with recombinant morphogenetic proteins, autologous MSCs and xenograft bone substitute was associated with a significant reduction in both pain and joint symptoms and reduced the incidence of fractural stages. At 36 months, 33 patients achieved clinical and radiographic healing. CONCLUSION: This long-term follow-up study confirmed that CD technique combined with recombinant morphogenetic proteins, autologous MSCs and xenograft bone substitute may be an effective treatment for patients with early stage osteonecrosis of the femoral head.

Megaprosthesis in large bone defects: opportunity or chimaera?

INTRODUCTION: The development of new megaprosthesis for the treatment of large bone defects provides important options to orthopaedic oncologic surgeons for the replacement of skeletal segments, such as the long bones of the upper and lower limbs and the relative joints. We implanted megaprosthesis using either a one-step or two-step technique depending on the patient's condition. The aim of this study was to evaluate retrospectively both clinical and radiological outcomes in patients who underwent lower limb megaprosthesis implant. MATERIALS AND METHODS: A total of 32 patients were treated with mono- and bi-articular megaprosthesis subdivided as follows: proximal femur, distal femur, proximal tibia and total femur. The mean follow-up of patients was about 18 months (range 3 months to 5 years). Clinical and serial radiographic evaluations were conducted using standard methods (X-ray at 45 days, 3, 6, 12, 18 and 24 months) and blood parameters of inflammation were monitored for at least 2 months. RESULTS: Although the mean length of follow-up was only 18 months, the first patients to enter the study were monitored for 5 years and showed encouraging clinical results, with good articulation of the segments, no somato-sensory or motor deficit and acceptable functional recovery. During surgery and, more importantly, in pre-operative planning, much attention should be given to the evaluation of the extensor apparatus, preserving it and, when necessary, reinforcing it with tendon substitutes. DISCUSSION: Megaprosthesis in extreme cases of severe bone loss and prosthetic failure is a potential solution for the orthopaedic surgeon. In oncological surgery, the opportunity to restore functionality to the patient (although not ad integrum) is important for both the patient and the surgeon. The high mortality associated with cancer precludes long-term patient follow-up; therefore, there is a lack of certainty about the survival of this type of prosthesis and any medium- to long-term complications that may occur. Nevertheless, patients should be considered as an oncologic patient, not because of the disease, but because of the limited therapeutic options available. CONCLUSIONS: Megaprosthesis provides a valuable opportunity to restore functionality to patients with highly disabling diseases.

Mussel mimetic tissue adhesive for fetal membrane repair: initial in vivo investigation in rabbits.

OBJECTIVE: Iatrogenic preterm prelabour rupture of fetal membranes (iPPROM) remains the main complication after invasive interventions into the intrauterine cavity. The aim of this study was to evaluate the sealing capability and tissue interaction of mussel-mimetic tissue adhesive (mussel glue) in comparison to fibrin glue on punctured fetal membranes in vivo. STUDY DESIGN: A mid-gestational rabbit model was used for testing the materials. The fetal sacs of pregnant rabbits at day 23 were randomly assigned into experimental groups: unoperated (negative control), unclosed puncture (positive control), commercially available fibrin glue (FG) with decellularized amnion scaffold (DAM), mussel glue (MG) with DAM, or mussel glue alone. Evaluation was done at term (30 days' gestation) assessing fetal survival, fetal membrane integrity and histology of the membranes. RESULTS: Fetal survival was not significantly lower in any of the treatment groups compared to the negative control. All plugging materials could be found at the end of the pregnancy and no adverse effects on the fetus or the pregnant does could be observed. Sac integrity was higher in all treatment groups compared to the positive control group but significant only in the FG+DAM group. Cellular infiltration could be seen in fibrin glue and DAM in contrast to mussel glue which was only tightly adhering to the surrounding tissue. These cells were mostly of mesenchymal phenotype staining positive for vimentin. CD68 positive macrophages were found clustered around all the plugging materials, but their numbers were only significantly increased for the mussel glue alone group compared to negative controls. CONCLUSIONS: Mussel glues performance in sealing fetal membranes in the rabbit model was comparable to that of fibrin glue. Taking into account its other favorable properties, it is a noteworthy candidate for a clinically applicable fetal membrane sealant.

Breast metastases from oligodendroglioma: an unusual extraneural spread in two young women and a review of the literature.

BACKGROUND: Extraneural dissemination of oligodendroglioma is rare. Cases of breast metastases have never been described in the literature. CASE REPORTS: We report the first two cases of young women with initial diagnosis of anaplastic oligodendroglioma who experienced mammary gland metastases and a review of the literature. RESULTS: Immunohistochemical analysis performed on material from both primary and metastatic sites did not allow to draw any conclusion on possible etiopathogenetic hypothesis. A review of literature yielded 35 cases of extracranial metastatic oligodendroglioma from 1989 to 2012. CONCLUSION: Though rare, extracranial dissemination from oligodendroglioma may occur not only in long surviving heavily pre-treated patients. The review of literature and these two cases suggest that spread is primarily to bone and then from bone to other organs through hematogenous route mostly due to leptomeningeal or dura mater invasion. Chemotherapy regimens similar to those commonly used for non metastatic oligodendroglioma are recommended for patients with good performance status.

Combined biaxial and uniaxial mechanical characterization of prosthetic meshes in a rabbit model.

The present experimental study is aimed at a combined uniaxial and biaxial mechanical characterization of the deformation behavior of two types of prosthetic meshes, SPMM (heavy-weight) and Gynemesh M (light-weight, partly absorbable), after integration in the host tissue. Explants from a full-thickness-abdominal-wall-defect-rabbit-model were tested in the two loading conditions. Corresponding protocols and data analysis procedures for biaxial inflation tests and uniaxial tensile tests were developed. Biaxial responses were observed to be by factor 2-4 stiffer compared to corresponding uniaxial experiments, depending on the material tested. In biaxial loading conditions, SPMM explants were stiffest. Gynemesh M explants and native tissue were similarly compliant at low membrane tensions (<5N/cm) (abdominal wall: 40±23N/cm, Gynemesh M: 59±44N/cm, SPMM: 145±36N/cm). At high membrane tensions (>5N/cm), there were distinct differences in the stiffness of the three groups, SPMM explants being the stiffest, followed by Gynemesh M explants and native tissue being the most compliant. In uniaxial loading conditions, the two explants were similarly stiff and distinctly stiffer than native tissue at low membrane tensions (<5N/cm) (abdominal wall: 9±1N/cm, Gynemesh M: 21±5N/cm, and SPMM: 24±5N/cm). At high membrane tension (>5N/cm), differences between all groups vanished. Biaxial and uniaxial tests yield different results with respect to the mechanical behavior of mesh explants. These findings demonstrate that an evaluation of the mechanical biocompatibility of prosthetic meshes should be based on an experimental configuration (uniaxial or biaxial tension) which reproduces the expected in vivo conditions of mechanical loading and deformation.

Monotherapy vs. polytherapy in the treatment of forearm non-unions and bone defects.

OBJECTIVE: To determinate the efficacy of "polytherapy", a surgical technique that utilize all the components of the diamond concept (mesenchymal stem cells, bone morphogenetic proteins and scaffold) versus a "monotherapy", a surgical technique that utilize only one component of the diamond conceptin the treatment of severe forearm non-unions. METHODS: We studied a database of 52 patients with 52 forearm non-unions; we classified the patients with the NUSS SCORE and we divided the patients in two group according to the treatment received. So we distinguished a group of patients treated according to the principles of "monotherapy" (33 patients) and a group of patients treated according to the principles of "polytherapy" (19 patients). The minimum follow up was 12 months. RESULTS: In the monotherapy group 21/33 non-unions (63.64%) went on to develop a radiographic and clinical healing within a period of 12 months, the calculated DASH SCORE showed a mean value of 55.15 points. In the polytherapy group 17/19 (89.47%) nonunions went on to develop clinical and radiographic healing within 12 months, and the average DASH score showed a mean value of 45.47 points. CONCLUSION: The polytherapy technique with the use of recombinant morphogenetic proteins, autologous MSCs and scaffold in the same surgical time appears to be an effective treatment for patients with severe forearm non-unions.

The use of bone-graft substitutes in large bone defects: any specific needs?

INTRODUCTION: The gold standard for restoring bone defects is still considered to be autologous bone grafting. However, clinical benefits are not guaranteed and donor-site complications and morbidity is not infrequent. Research is on-going for the development of alternative bone substitutes of both biological and synthetic origin. The purpose of this study was to evaluate the type of materials used and their efficacy for the treatment of large bone defects in traumatology and orthopaedic surgery. MATERIALS AND METHOD: A literature review was carried out of Embase and PubMed databases. Inclusion criteria were articles in English language focusing on the use of bone substitutes in trauma and orthopaedic surgery for the treatment of bone defects and included details on the structural, biological or biomechanical properties of the pure product. Furthermore, based on two clinical challenges, fracture non-union and impaction grafting we elaborated on the use of polytherapy for large bone defects as guided by the diamond concept. RESULTS: All the products indicated in this manuscript possess osteoconductive activities but have different resorption times and biomechanical properties. Bone graft substitute materials are used for a wide range of clinical applications even when the level of clinical evidence is low. The size and location of the defect and the local biological and mechanical environment as well as the biomechanical characteristics of the material determine the type of device that can be implanted in a bone defect. CONCLUSION: Proper assessment of the biological and mechanical environment and accurate patient selection are necessary to judge the extent of therapy the injury warrants. A sound understanding of various aspects of biomaterial properties and their relation and influence towards bone healing is of utmost importance. We suggest the application of polytherapy for the treatment of large bone defects and advocate the use of the diamond concept as a guideline.

Persistence of polypropylene mesh anisotropy after implantation: an experimental study.

OBJECTIVE: To determine whether anisotropy persisted after incorporation into the host, using a standardised rabbit model for abdominal wall reconstruction. DESIGN: Investigator-initiated prospective-controlled experimental study. SETTING: Centre for Surgical Technologies, Medical Faculty KU-Leuven. SAMPLE: Fifteen New Zealand White rabbits. METHODS: In each rabbit, four full thickness primarily repaired abdominal wall defects were covered by a 4 × 5-cm Prolift+M implant (Johnson & Johnson, Norderstedt, Germany), either with the stiffest (n = 6 rabbits) or most elastic (n = 6) direction parallel to the body axis. Prolift+M contains 32 g/m² polypropylene, reinforced with polyglecaprone fibres. Harvesting was performed after 30, 60 and 120 days (n = 2 each time-point). The abdominal wall of three unoperated rabbits was used as negative control. MAIN OUTCOME MEASURES: Contraction, compliance and maximal strain and stress determined by uniaxial tensiometry. RESULTS: Anisotropy properties persist at lower, more physiological displacements, but not at higher displacements. The stiffness of a mesh-augmented repair in the lower strain range remains above that of native tissue. Eventual mesh contraction was limited to 4.3%. CONCLUSIONS: Anisotropic properties of Prolift+M persist in vivo and shrinkage is minimal. Compliance of mesh-augmented repair remains less than that of native tissue. The functional consequences of this remain to be studied.

Polytherapy in bone regeneration: clinical applications and preliminary considerations.

Polytherapy, namely the simultaneous application of three fundamental elements necessary for bone regeneration (growth factors, osteogenic cells and osteoconductive scaffolds) seems to lead to a very high success rate in the treatment of complex non-union (NU) cases and critical bone defects. NU are reported in 5-10% of long bone fractures. The use of autologous bone grafts has been long-considered the gold standard for the treatment of these cases. However the harvesting procedure from the iliac crest increases surgery time and presents some donor site complications which may be elevated. In recent years, surgeons have some alternatives to autologous grafting such as: application of organic or synthetic bone substitute, application of mesenchymal stromal cells (MSC) or growth factors (GF). In the literature there are many studies available about their application in monotherapy, but unfortunately the healing rate doesn't exceed 90%. Polytherapy seems to be a logical option to improve the healing rate, nevertheless, there are not still extensive studies that validate this strategy and moreover, some questions are not resolved.

Treatment of long bone non-unions with polytherapy: indications and clinical results.

The incidence of long bone non-unions has been estimated to range between 5 and 10%. Autologous bone graft usually harvested from the iliac crest continues to be the gold standard for biological enhancement of atrophic non-unions. However, its use has been hampered by minor and major donor site complications. Moreover despite possessing the properties of osteogenecity, osteoconductivity and some osteoinductivity the overall results of treatment have not been consistent with disappointing success rates at times. The concept of polytherapy for the treatment of non-unions, namely the simultaneous application of the three fundamental elements of the diamond concept, osteoprogenitor cells, growth factor and osteoconductive scaffold, appears to be an attractive alternative but more studies are desirable to validate this strategy.

Outcome of upfront combination chemotherapy followed by chemoradiation for locally advanced pancreatic adenocarcinoma.

PURPOSE: The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial. METHODS: Treatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.