Meningeal carcinomatosis in breast cancer: prognostic factors and outcome

Meningeal carcinomatosis (MC) occurs in up to 5% of breast cancer patients. Few studies have evaluated prognostic markers in breast cancer patients with MC. Our aim was to describe the treatment of breast cancer patients with MC, and identify prognostic factors related to survival. Sixty breast cancer patients that had a diagnosis of MC between January 2003 and December 2009 were included. The median age was 46 years (range 27-76). Most patients had invasive ductal carcinoma (78.3%) and high histological/nuclear grade (61.7/53.3%). Estrogen and progesterone receptors were positive in 51.7 and 43.3% of patients, respectively, and 15% were HER-2-positive. Symptoms at presentation were headache, cranial nerve dysfunction, seizures, and intracranial hypertension signals. Diagnosis was made by CSF cytology in 66.7% of cases and by MRI in 71.7%. Intrathecal (IT) chemotherapy was used in 68.3% of patients, and 21.6% received a new systemic treatment (chemo- or hormone therapy). Median survival was 3.3 months (range 0.03-90.4). There was no survival difference according to age, nuclear grade, hormonal and HER-2 status, CSF features, sites of metastasis, systemic and IT chemotherapy, or radiotherapy. However, histological grade and performance status had a significant impact on survival in the multivariate analysis. Only four papers have addressed prognostic factors in breast cancer patients with MC in the last two decades. The results of those reports are discussed here. High histological grade and poor performance status seem to impact survival of breast cancer patients with MC. Prospective studies are necessary to clarify the role of IT and systemic treatment in the treatment of those patients.

Neoplastic Ascites in Osteosarcoma A Case Report

Background Osteosarcoma is a malignant tumor of connective tissue Whose tumor cells produce bone tissue. It can be classified as osteoblastic, chondroblastic, or fibroblastic, according to the predominant histologic type of cells. Its dissemination is hematogenous; and the lungs are the most frequent site of clinically evident metastasis. Extrapulmonary metastases are rare and more frequently diagnosed at necropsy. We present a case of osteosarcoma with peritoneal dissemination that developed neoplastic ascites. Case A 46-year-old patient came to the hospital with a 4-month history of lumbar pain and weakness in the lower limbs. Computed tomography showed blastic lesions in the L3 vertebral body. Surgical resection and histologic analysis revealed a mixed osteoblastic and chondroblastic osteosarcoma. After only one session of chemotherapy, the patient presented a marked clinical worsening with extensive metastatic dissemination and occurrence of voluminous ascites. The cytologic examination of the ascitic fluid demonstrated frequent poorly differentiated tumor cells. The patient died a little more than 2 months after the diagnosis. Conclusion This case is the only report of osteosarcoma primarily focused on the vertebral column affected by peritoneal metastasis shown by cytologic examination of ascitic fluid. (Acta Cytol 2010;54:845-848)

(18)F-FDG PET After 2 Cycles of ABVD Predicts Event-Free Survival in Early and Advanced Hodgkin Lymphoma

Our objective was to assess the prognostic value of (18)F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). Methods: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. Results: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. Conclusion: PET2 is an accurate and independent predictor of EFS in HL. A negative interim (18)F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

Corneal myofibroblast generation from bone marrow-derived cells

The purpose of this study was to determine whether bone marrow-derived cells can differentiate into myofibroblasts, as defined by alpha-smooth muscle actin (SMA) expression, that arise in the corneal stroma after irregular phototherapeutic keratectomy and whose presence within the cornea is associated with corneal stromal haze. C578L/6J-GFP chimeric mice were generated through bone marrow transplantation from donor mice that expressed enhanced green fluorescent protein (GFP) in a high proportion of their bone marrow-derived cells. Twenty-four GFP chimeric mice underwent haze-generating corneal epithelial scrape followed by irregular phototherapeutic keratectomy (PTK) with an excimer laser in one eye. Mice were euthanized at 2 weeks or 4 weeks after PTK and the treated and control contralateral eyes were removed and cryo-preserved for sectioning for immunocytochemistry. Double immunocytochemistry for GFP and myofibroblast marker alpha-smooth muscle actin (SMA) were performed and the number of SMA+GFP+, SMA+GFP, SMA-GFP+ and SMA GFP cells, as well as the number of DAPI+ cell nuclei, per 400x field of stroma was determined in the central, mid-peripheral and peri-limbal cornea. In this mouse model, there were no SMA+ cells and only a few GFP+ cells detected in unwounded control corneas. No SMA+ cells were detected in the stroma at two weeks after irregular PTK, even though there were numerous GFP+ cells present. At 4 weeks after irregular PTK, all corneas developed mild to moderately severe corneal haze. In each of the three regions of the corneas examined, there were on average more than 9x more SMA+GFP+ than SMA+GFP myofibroblasts. This difference was significant (p < 0.01). There were significantly more (p < 0.01) SMA GFP+ cells, which likely include inflammatory cells, than SMA+GFP+ or SMA+GFP cells, although SMA GFP cells represent the largest population of cells in the corneas. In this mouse model, the majority of myofibroblasts developed from bone marrow-derived cells. It is possible that all myofibroblasts in these animals developed from bone marrow-derived cells since mouse chimeras produced using this method had only 60-95% of bone marrow-derived cells that were GFP+ and it is not possible to achieve 100% chimerization. This model, therefore, cannot exclude the possibility of myofibroblasts also developed from keratocytes and/or corneal fibroblasts. (C) 2010 Elsevier Ltd. All rights reserved.

The Bone Histology Spectrum in Experimental Renal Failure: Adverse Effects of Phosphate and Parathyroid Hormone Disturbances

Bone disease is a common disorder of bone remodeling and mineral metabolism, which affects patients with chronic kidney disease. Minor changes in the serum level of a given mineral can trigger compensatory mechanisms, making it difficult to evaluate the role of mineral disturbances in isolation. The objective of this study was to determine the isolated effects that phosphate and parathyroid hormone (PTH) have on bone tissue in rats. Male Wistar rats were subjected to parathyroidectomy and 5/6 nephrectomy or were sham-operated. Rats were fed diets in which the phosphate content was low, normal, or high. Some rats received infusion of PTH at a physiological rate, some received infusion of PTH at a supraphysiological rate, and some received infusion of vehicle only. All nephrectomized rats developed moderate renal failure. High phosphate intake decreased bone volume, and this effect was more pronounced in animals with dietary phosphate overload that received PTH infusion at a physiological rate. Phosphate overload induced hyperphosphatemia, hypocalcemia, and changes in bone microarchitecture. PTH at a supraphysiological rate minimized the phosphate-induced osteopenia. These data indicate that the management of uremia requires proper control of dietary phosphate, together with PTH adjustment, in order to ensure adequate bone remodeling.

Treatment of scaphoid nonunion with vascularised and nonvascularised dorsal bone grafting from the distal radius

We conducted a prospective randomised study comparing the clinical, functional and radiographic results of 46 patients treated for scaphoid nonunion using a vascularised bone graft from the dorsal and distal aspect of the radius (group I), relative to 40 patients treated by means of a conventional non-vascularised bone graft from the distal radius (group II). Surgical findings included 30 sclerotic, poorly-vascularised scaphoids in group I versus 20 in group II. Bone fusion was achieved in 89.1% of group I and 72.5% of group II patients (p = 0.024). Functional results were good to excellent in 72.0% of the patients in group I and 57.5% in group II. Considering only patients with sclerotic, poorly-vascularised scaphoids, the mean final outcome scores obtained were 7.5 and 6.0 for groups I and group II, respectively. We conclude that vascularised bone grafting yields superior results and is more efficient when there is a sclerotic, poorly-vascularised proximal pole in patients in scaphoid nonunion.

Bone mineral density analysis in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 after total parathyroidectomy

P>Objective Limited data have been reported on the effect of parathyroidectomy (PTx) on bone mineral density (BMD) in the setting of patients with hyperparathyroidism (HPT) associated with multiple endocrine neoplasia type 1 (MEN1). This study investigates the impact of total PTx on BMD in patients with HPT/MEN1. Design and patients A case series study was performed in a tertiary academic hospital. A total of 16 HPT/MEN1 patients from six families harbouring MEN1 germline mutations were subjected to total PTx followed by parathyroid auto-implant in the forearm. Measurements Bone mineral density values were assessed using dual-energy X-ray absorptiometry. Results Before PTx, reduced BMD (Z-score <-2 center dot 0) was highly prevalent in the proximal one-third of the distal radius (1/3 DR) (50%), lumbar spine (LS) (43 center dot 7%), ultradistal radius (UDR) (43 center dot 7%), femoral neck (FN) (25%) and total femur (TF) (18 center dot 7%) in the patients. Fifteen months after PTx, we observed a BMD improvement in the LS (from 0 center dot 843 to 0 center dot 909 g/cm2; +8 center dot 4%, P = 0 center dot 001), FN (from 0 center dot 745 to 0 center dot 798 g/cm2; +7 center dot 7%, P = 0 center dot 0001) and TF (from 0 center dot 818 to 0 center dot 874 g/cm2; +6 center dot 9%, P < 0 center dot 0001). No significant change was noticed in the 1/3 DR and UDR after PTx. Conclusions This data confirmed BMD recovery in the LS and FN after PTx in HPT/MEN1 patients. We also documented a significant BMD increase in the TF and no change in both the 1/3 DR and UDR BMD after PTx. Our data suggest that LS and proximal femur are the most informative sites to evaluate the short-term BMD outcome after PTx in HPT/MEN1 subjects.

Effects of bone remodelling on calcium mass transfer during haemodialysis

Background. During haemodialysis, calcium balance can affect, or be affected by, mineral metabolism. However, when dialysate calcium concentration (d[Ca]) is chosen or kinetic models are employed to calculate calcium balance, bone remodelling is rarely considered. In this study, we examined whether bone remodelling affects calcium mass transfer during haemodialysis. Methods. We dialysed 23 patients using a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L. Calcium mass transfer was measured and associated with remodelling bone factors. Results. Calcium balance varied widely depending on the d[Ca]. Calcium removal was -578 +/- 389, -468 +/- 563, +46 +/- 400 and +405 +/- 413 mg when a d[Ca] of 1.0, 1.25, 1.5 or 1.75 mmol/L was used, respectively (1.0 and 1.25 VS 1.5 and 1.75 mmol/L, P<0.001; 1.5 vs 1.75 mmol/L, P<0.05). Univariate analysis showed that calcium balance correlated with calcium gradient, parathyroid hormone (PTH), osteocalcin and dialysis vintage. Multivariate analysis revealed that calcium balance was dependent on calcium gradient, PTH and osteocalcin. Conclusions. These results suggest that bone remodelling could affect calcium mass transfer during haemodialysis.

Lymphadenectomy in Colorectal Cancer Liver Metastases Resection: Incidence of Hilar Limph Nodes Micrometastasis

Background: Liver resection is considered the best treatment for metastatic colorectal cancer. Several prognostic factors have been investigated, and many studies have shown that hepatic hilum lymph nodes involvement has a negative impact on prognosis. The present study evaluated the frequency of microscopic involvement of hilar lymph nodes, through systematic lymphadenectomy and analysis of micrometastases in patients undergoing hepatectomy due to colorectal metastasis. Methods: A total of 28 patients underwent hepatic resection with hilar lymphadenectomy. Lymph nodes considered negative by conventional hematoxylin and eosin (H&E) staining were analyzed by serial sectioning with 100-mu m intervals and immunohistochemistry (IHC) with antihuman pancytokeratin antibody AE1/AE3. Results: In average, 6.18 lymph nodes were dissected per patient. No morbidity or mortality was associated to lymphadenectomy. In two patients, conventional H&E analysis showed presence of microscopic lymph node metastasis. H&E analysis allowed the identification of three other patients with lymph node micrometastases. The overall frequency of microscopic metastases, including micrometastasis, was 18%. Conclusions: Systematic lymphadenectomy allowed the detection of microscopic lymph node metastases, resulting in more accurate staging of extrahepatic disease. The inclusion of IHC increased the detection of lymph node micrometastasis. J. Surg. Oncol. 2009;100:534-537. (C) 2009 Wiley-Liss, Inc.

Strength Training Preserves the Bone Mineral Density of Postmenopausal Women Without Hormone Replacement Therapy

Objective: The study was designed to evaluate the effects of strength training (ST) on the bone mineral density (BMD) of postmenopausal women without hormone replacement therapy. Method: Subjects were randomized into untrained (UN) or trained (TR) groups. The TR group exercised three ST sessions per week for 24 weeks, and body composition, muscular strength, and BMD of the lumbar spine and femur neck were evaluated. Results: Body weight, mass index, and fat percentage were lower after 24 weeks only in the TR group (p < .05). SR also improved the one repetition maximum test in 46% and 39% of upper and lower limbs, respectively. The percentage of demineralization was higher in the UN group than in the TR group at the lumbar spine and femoral neck (p < .05). Discussion: Results indicated that 24 weeks of ST improved body composition parameters, increased muscular strength, and preserved BMD in postmenopausal women.

Percutaneous vertebroplasty for multiple myeloma of the cervical spine

Spinal involvement is a common presentation of multiple myeloma (MM); however, the cervical spine is the least common site of myelomatous involvement. Few studies evaluate the results of percutaneous vertebroplasty (PV) in the treatment of MM of the spine. The purpose of this series is to report on the use of PV in the treatment of MM of the cervical spine and to review the literature. From January 1994 to October 2007, four patients (three men and one woman; mean age, 45 years) who underwent five PV for painful MM in the cervical spine were retrospectively reviewed. The pain was estimated by the patient on a verbal analogic scale. Clinical follow-up was available for all patients (mean, 27.5 months; range, 1-96 months). The mean volume of cement injected per vertebral body was 2.3 +/- 0.8 mL (range, 1.0-4.0 mL) with a mean vertebral filling of 55.0 +/- 12.0% (range, 40.0-75.0%). Analgesic efficacy was achieved in all patients. One patient had a spinal instability due to a progression of spinal deformity noted on follow-up radiographs, without clinical symptoms. Cement leakage was detected in three (60%) of the five treated vertebrae. There was no clinical complication. The present series suggests that PV for MM of the cervical spine is safe and effective for pain control; nonetheless, the detrimental impact of the disease on bone quality should prompt close radiological follow-up after PV owing to the risk of spinal instability.

Analysis of Craniofacial and Extremity Growth in Patients with Growth Hormone Deficiency during Growth Hormone Therapy

Background/Aims: There are many controversies regarding side effects on craniofacial and extremity growth due to growth hormone ( GH) treatment. Our aim was to estimate GH action on craniofacial development and extremity growth in GH-deficient patients. Methods: Twenty patients with GH deficiency with a chronological age ranging from 4.6 to 24.3 years (bone age from 1.5 to 13 years) were divided in 2 groups: group 1 (n = 6), naive to GH treatment, and group 2 (n = 14), ongoing GH treatment for 2-11 years. GH doses (0.1 -0.15 U/kg/day) were adjusted to maintain insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels within the normal range. Anthropometric measurements, cephalometric analyses and facial photographs to verify profile and harmony were performed annually for at least 3 years. Results: Two patients with a disharmonious profile due to mandibular growth attained harmony, and none of them developed facial disharmony. Increased hand or foot size (>P97) was observed in 2 female patients and in 4 patients (1 female), respectively, both not correlated with GH treatment duration and increased levels of insulin-like growth factor 1. Conclusions: GH treatment with standard doses in GH-deficient patients can improve the facial profile in retrognathic patients and does not lead to facial disharmony although extremity growth, mainly involving the feet, can occur. Copyright (C) 2009 S. Karger AG, Basel

USE OF ANTIBIOTIC SPACERS FOR KNEE ENDOPROSTHESIS INFECTIONS TREATMENT

Objective: The aim of this study is to evaluate the use of cement spacers impregnated with antibiotics for the treatment of infections in the nonconventional endoprostheses of the knee. Methodology: We have treated seven patients since 2004 (of which six were submitted to surgery in our service and one patient had been submitted to a primary tumor surgery in another removal service) with deep infection in knee tumor prosthesis. All patients were submitted to endoprosthesis removal and reconstructed with antibiotic cement spacer All patients were monitored both clinically and by lab tests as for monitoring the evolution, being considered able for reviews after 6 (six) months without infections signs. Results: We have noted a small predominance of infectious processes on the prosthesis inserted on proximal tibia as compared with distal femur (57.1% x 42.9%). The mean follow-up time of patients was 68.2 months. During the follow up, one patient died as a result of the root disease. Six patients out of seven were regarded as cured and one persisted with infection signs and symptoms. Conclusion: The results obtained up to date have motivated us to continue using this method of treatment.

One-Stage Revision of Infected Total Hip Arthroplasty with Bone Graft

There are many different opinions in the literature regarding the best procedure for revision of infected hip arthroplasty and hence in achieving long-term stabilization of a new implant. Thirty-two patients with 32 loose and infected total hip arthroplasties underwent revision with a bone graft in a 1-stage procedure. The bone graft was used in the acetabulum and femure in 25 patients, in the acetabulum alone in 4 patients and in the femur alone in 3 patients. A metal mesh was necessary in 15 patients to contain the morselized bone graft. At the time of surgical revision, 9 patients had a draining sinus, 6 had a closed sinus, and 17 had never had sinuses in the surgical wound. Antibiotic therapy was administered intravenously and orally for 6 months. Mean follow-up was 103 months (range, 63-183 months), and infection recurred in 2 (6.2%) cases. Further studies are necessary, and continuation of this method is justified.

Use of Allogeneic Bone Graft in Maxillary Reconstruction for Installation of Dental implants

The aim of this study is to evaluate the efficacy of the application of allogenous bone at the maxillo-mandibular reconstructions for future rehabilitation with dental implants. The patients were submitted to reconstruction of maxilla, using allogeneic bone grafts, in 3 different techniques: onlay grafts for lateral ridge augmentation, onlay and particulate bone for sinus lift grafting, and particulate alone for sinus lift grafts. Clinical and radiographic control was done at the postoperative phase for at least 8 months, until the patient could be submitted to the installation of dental implants. The results showed success in the majority of the cases, and dental implants could be installed. This can be considered an excellent alternative when compared with the use of autogenous grafts; because handling is easier, there is a great amount of material available and a possibility of using local anesthesia, and consequently there is a reduction of patient morbidity. (C) 2008 American Association of Oral and Maxillofacial Surgeons