Desmoplastic fibroma of the jaw: the experience of the Istituto Beretta

Osteogenic sarcoma of the maxilla and mandible is a peculiar entity within the context of the malignant bone tumors of other sites. In our series of nine cases the mean age at appearance was 34.1 years; 44.5% of the tumors affected the maxilla, and 55.5% affected the mandible. Most of the tumors were principally rapidly growing and painless or minimally painful masses. Histopathologically, the fibroblastic type was the most frequent, with prevalence of Broders' Grades III and IV. Radical surgery was the only therapeutic procedure in 87.5% of the series, producing a survival of 85%. Overall survival for all the therapeutic categories was 75%, with a mean disease-free interval of 8 years. In the remaining cases, local recurrence and intracranial invasion were the main causes of death.     

Ewing's sarcoma of the mandible and maxilla. A report of three cases from the Istituto Beretta

Ewing's sarcoma of the jaw is a rare primary malignant bone tumor. Three cases, two in the mandible and one in the maxilla, are presented, together with complete histologic, radiographic, and clinical evaluations. While the prognosis for patients with this lesion remains poor, an increased rate of survival is now associated with multiple-drug chemotherapeutic regimens.     

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide/Bendamustine in Pediatric and Young Adult Patients with Hematologic Malignancies

More than half of patients undergoing hematopoietic cell transplantation at our institution are ethnic or racial minorities, making the search for matched unrelated donors more challenging. Since the introduction of haploidentical bone marrow transplant (haplo-BMT) into our pediatric BMT program in 2015, 69.2% of recipients have been minorities. Herein, we describe our experience with the first 13 pediatric and young adult patients with hematologic malignancies who have undergone T cell–replete haplo-BMT after myeloablative conditioning (MAC) at our institution. We have previously documented that in experimental haplo-BMT, post-transplant bendamustine (PT-BEN) is at least as effective as post-transplant cyclophosphamide (PT-CY) against graft-versus-host disease (GVHD) and elicits superior graft-versus-leukemia (GVL) effects. We report on, for the first time in humans, 4 patients treated with PT-CY and PT-BEN after haplo-BMT as part of our ongoing institutional phase I/II study (NCT02996773). The remaining 9 patients reviewed in this report received PT-CY. Our findings indicate that MAC haplo-BMT is well tolerated by children and young adults with advanced hematologic malignancies with no observed nonrelapse mortality or grades III to IV GVHD. All patients who underwent haplo-BMT remain alive and disease-free with a median follow-up of 15.6 months (range, 1.5 to 31.2). Preliminary findings from our ongoing clinical trial demonstrate that partial substitution of PT-BEN for PT-CY is feasible and safe after haplo-BMT as an immune modulatory strategy to alleviate GVHD and potentially more effectively preserve GVL.     

Innovations in radiotherapy and advances in immunotherapy for the treatment of brain metastases

Radiotherapy for brain metastases has evolved tremendously over the past four decades, allowing for improved intracranial control of disease with reduced neurotoxicity. The main technological advance was provided by volumetric modulated arc therapy (VMAT), a computer-controlled delivery method that has opened the door for single-isocenter multi-metastases stereotactic radiosurgery (SRS) and hippocampal avoidance whole brain radiation therapy (HA-WBRT). Other notable advances have occurred in the combination of immune checkpoint inhibitors (ICI) and radiosurgery. When these two modalities are combined in the proper sequence (within 30 days from each other), it provides promising results in the treatment of intracranial metastases from melanoma. There is emerging evidence of a synergistic interaction between ICI and SRS, providing better intracranial tumor control and lengthening the survival of patients afflicted by this common complication of cancer.

     

The crosslinking of nuclear protein to DNA using ionizing radiation

Summary DNA-protein complexes were generated in intact Chinese hamster ovary (CHO) cells by the use of ionizing radiation. The DNA-protein crosslinks, as measured by a filter-binding assay, occurred immediately following the irradiation, were produced in a dose-dependent manner and were reversible. The reversibility of the crosslinks in the intact cells was dependent upon general protein synthesis. Three proteins that were attached to DNA in unirradiated cells were analyzed according to the presence of DNA attached to the proteins before, during and after exposure to ionizing radiation. All three proteins contained more DNA reversibly attached to the proteins after exposure to 5 Gy ionizing radiation as compared to unirradiated cells. One of the proteins was increasingly attached to DNA using 2.5–50 Gy X-ray. These data suggest that the increased DNA-protein crosslinking observed with ionizing radiation may involve the increase in particular protein(s) crosslinked to DNA as well as an increase in the amount of DNA attached to specific proteins.Abbreviations PBS phosphate-buffered saline - CHO Chinese hamster ovary     

Wear debris and cytokine production in the interface membrane of loosened prostheses

In this study, thirty-nine patients were examined. All of them suffered from hip joint prostheses loosening and underwent revision surgery. Bioptic samples were collected at the interface between bone and implant either at the stem or cotyle level. Immunohistochemistry was performed to detect IL-1alpha, IL-1beta, IL-6 and TNF, cytokines that directly cause bone resorption and indirectly induce synthesis of other bone resorbing cytokines. Quantitative analysis of the positive cells and correlation with clinical data was performed. It resulted that there is a great variability in positive cells for cytokines according to the harvest site; anyway, cytokines tend to be higher in patients carrying a joint prosthesis with polyethylene acetabular component and it is associated with plastic wear particles, even though there is no direct correlation between wear amount and cytokine levels. There is a statistically significant negative correlation between metal wear and a cytokine (IL-6); cytokines levels do not depend on the implant time to failure and do not correlate with pain score. As expected, cytokines levels tend to be lower in subjects being treated with non-steroidal antiinflammatory drugs. It can be concluded that plastic wear is the factor inducing the highest cytokine levels in the tissues around the prosthesis at the interface; cytokines that are an indicator of osteolysis risk.     

Short Stems Versus Conventional Stems in Cementless Total Hip Arthroplasty: A Long-Term Registry Study

Background

Short stems in total hip arthroplasty (THA) have recently gained increasing popularity, allowing mini-invasive exposures and bone-sparing approaches. However, long-term studies and recommendations for the routine use are not available. The aim of this report was to compare the survival rates and the reasons for revision of short stems versus conventional stems in cementless THAs, in a registry-based population.

The experience of the RIPO,a shoulder prosthesis registry with 6-year follow-up

Background

Implant registries have proved valuable in assessing the outcomes of arthroplasty procedures. Moreover, by identifying lesser quality implants they have indirectly improved the quality of care. The registry of prosthetic shoulder implants was established in 2008.

Methods

It records information on all types of primary and revision arthroplasty procedures involving the glenohumeral joint, including reverse and total arthroplasty, hemiarthroplasty, resurfacing, removal, and any other surgical procedures that are required to manage these patients. The collected data include patient demographics, weight, height, operated side, cuff status, and diagnosis/reason for revision surgery, information on previous surgical procedures involving either shoulder, comorbidities, antibiotic and thromboembolic prophylaxis, blood transfusions, surgical approach, cuff repair procedures performed during arthroplasty, bone grafts, drains, and perioperative complications, and data about the prosthetic components implanted, including the fixation method.

Results

Procedures were performed on 3754 shoulders. They included 2226 RSA, 320 TSA, 730 HA, 233 resurfacing procedures, 245 revisions, and 77 “other” procedures. The survival curves of the implants are greater than 90%, and no differences were found among prosthesis from different manufacturers. The diagnosis that prompted to arthroplasty was: osteoarthritis in 60.9% of cases and fractures, bone necrosis, sequelae of fracture and rotator cuff tear arthropathy for the rest of implants.

Discussion and conclusion

This study describes the epidemiological data and mid-term implant outcomes of the shoulder arthroplasty procedures performed in our region, from 2008 to 2014, and compares them with published data from national registries of similar size.

Level of evidence

III.

     

alpha6 Integrin Cleavage: Sensitizing human prostate cancer to ionizing radiation

Purpose: The goal was to determine if prostate tumor cells containing a mutant α6 integrin would be defective in tumor re-population following clinically relevant fractionated ionizing radiation (IR) treatments.

Material and methods: Human prostate cancer cells derived from PC3N cells were used which conditionally expressed a cleavable, wild type form of α6 integrin (PC3N-α6-WT) or a mutated non-cleavable form of α6 integrin (PC3N-α6-RR). The resulting tumor growth before, during and after fractionated doses of IR (3 Gy×10 days) was analyzed using the endpoints of tumor growth inhibition (T/C), tumor growth delay (T-C), tumor doubling time (Td) and tumor cell kill (Log₁₀ cell kill).

Results: The T/C values were 36.1% and 39.5%, the T-C values were 20.5 days and 28.5 days and the Td values were 5.5 and 10.5 days for the irradiated PC3N-α6-WT and PC3N-α6-RR cells, respectively. The Log₁₀ was 1.1 for the PC3N-α6-WT cells and 0.8 for the PC3N-α6-RR cells. The tumor response to IR was altered in tumors expressing the mutant α6 integrin as indicated by a significant increase in tumor growth inhibition, an increase in tumor growth delay, an increase in tumor doubling time and an increase in tumor cell kill.

Conclusions: Blocking integrin cleavage in vivo may be efficacious for increasing the IR responsiveness of slow growing, pro-metastatic human prostate cancer.     

Refinement of a rodent model of peripheral lymphedema.

A reliable, inexpensive experimental counterpart of peripheral lymphedema has been notoriously difficult to reproduce thereby stifling basic and clinical research into this frustrating clinical condition. Accordingly, in 45 adult Wistar-Fuzzy rats, we attempted to produce sustained hindlimb lymphedema by either groin nodal/lymphatic microsurgical ablation (S) (guided by visual blue dye lymphography) or limited field-groin irradiation (R) alone (4500 rads) or combined S followed by R or R followed by S with an additional non-manipulated group serving as controls. Observations were made for 30-100 days thereafter. Hindlimb volumes were determined serially using the truncated cone formula based on multiple circumferential measurements at standardized intervals along the affected hindlimb and the findings compared with similar measurements in the contralateral non-manipulated hindlimb. In randomly selected rats from each group, lymphatic drainage was assessed by lymphangioscintigraphy (LAS), soft tissue swelling by magnetic resonance imaging (MRI), and edema fluid total protein content by refractometry. Whereas S or R alone produced only transient or mild hindlimb edema without associated morbidity or mortality, S-R or R-S induced moderate to severe sustained protein-rich hindlimb lymphedema associated with 9-13% early mortality and notable late local limb morbidity. Lymphatic obstruction was documented by sustained maintenance of increased hindlimb volume, subcutaneous fluid accumulation (MRI), and impaired lymphatic drainage (LAS). This reproducible rodent model of secondary lymphedema reliably simulates a stable clinical condition for a window of up to 100 days and should thereby facilitate standardized testing of therapeutic/preventive protocols and basic research into lymphatic dynamics in secondary lymphedema.