Compliant Compression Reconstruction of the Proximal Femur Is Durable Despite Minimal Bone Formation in the Compression Segment

BackgroundCompliant compression fixation was developed to promote permanent bone-prosthesis osteointegration while preserving bone stock in patients needing endoprosthetic reconstructions. This has demonstrated durability in the distal femur, with reliable cortical hypertrophy adjacent to the implant. However, the extent of bone formation and prosthetic survivorship of proximal femoral replacements with compliant compression fixation has not been established.Questions/purposes(1) How much bone formation occurs across the compression segment in patients treated with a proximal femoral replacement implant using compliant compression fixation? (2) What were the Musculoskeletal Tumor Society (MSTS) scores at minimum 24-month follow-up of patients who received this reconstruction? (3) What is the implant survivorship free from implant removal or revision for any reason at final follow-up?MethodsFrom 2006 to 2018, we performed 213 proximal femoral replacements in patients with oncologic conditions of the proximal femur where the trochanters could not be preserved. Of these, 6% (12 of 213) were performed with an implant that used compliant compression fixation. We used this device in primary oncologic reconstructions in patients younger than 65 years of age without metastases who had nonirradiated bone with the requisite ≥ 2.5 mm of cortical thickness in the hope that it would provide more durable fixation and bone stock preservation than conventional reconstructions. All patients were followed for longer than 2 years except one who died in that interval. Median (range) follow-up was 6 years (2 to 10 years). Seven patients received diagnosis-specific chemotherapy in a consistent manner based on Children’s Oncology Group chemotherapy protocols. Using the NIH-developed ImageJ open-access software, we measured the area of bone under compression on 3-, 6-, 9-, 12-, 18-, and 24-month radiographs and the length of the traction bar potential-compression distance, reconciling independent measures from two investigators using the identical method as published for the distal femur with compression fixation. The duration of prosthesis retention was evaluated using a competing risk analysis for the 11 surviving patients.ResultsBone hypertrophy in the compression segment was scant. At the final analysis, cortical bone formation was a median (range) of 4 (-7 to 14) above baseline. The median (range) MSTS score was 27 (19 to 30). One implant failed after trauma, and the patient underwent revision of the implant.ConclusionDespite scant bone formation across the compression segment and drastically less formation than reported for distal femoral replacements, compliant compression fixation of the proximal femur demonstrated good survivorship in patients 65 years or younger with localized sarcoma and nonirradiated, adequate bone stock in this small, retrospective series. Patients achieved good functional outcomes at final follow-up. The potential benefit of this reconstruction method should be weighed against the initial period of limited weightbearing and the life expectancy of the patient.Level of EvidenceLevel IV, cohort study.     

Results of definitive radiotherapy with concurrent chemotherapy for maxillary sinus carcinomas with neck lymph node metastasis

The purpose of this study was to describe the results of definitive radiotherapy (RT) with concurrent chemotherapy for maxillary sinus carcinomas (MSCs) with neck lymph node metastasis to clarify its limitation. Local control (LC), progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan–Meier method and were compared between subgroups using the log rank test. Toxicity was classified using common terminology criteria of adverse events version 5.0. Eighteen patients with inoperable MSC with neck lymph node metastasis including 12 men and 6 women with a median age of 67 years were analyzed. The histologic diagnoses were as follows: 16 patients had squamous cell carcinomas and 2 had other histology. Four patients had stage T3 MSC, 6 had T4a and 8 had T4b. Among 18 patients, 7 received concurrent systemic chemotherapy and 11 received selective arterial chemo-infusion. The median follow-up period was 17 months. The 2-year LC, PFS and OS rates for the entire cohort were 34, 31 and 46%, respectively. No significant differences were observed for LC, PFS and OS rates between systemic chemotherapy and selective arterial chemo-infusion cohorts. Grade 3 or higher acute toxicity, including both non-hematological and hematological, was observed in nine patients (50%), while no grade 3 or higher late toxicity was observed. In conclusion, we described the results of definitive RT for MSCs with neck lymph node metastasis. Local recurrence of primary tumor was a frequent pattern of failure and it should be addressed in future study.     

Cdc7 kinase is required for postnatal brain development

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7^Fl/Fl Nestin^Cre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7^{Fl/F l}Nestin^Cre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.     

Non-suture end-to-end anastomoses between polytetrafluoroethylene graft and vessels for blood access

BACKGROUND: Non-suture end-to-end anastomoses between polytetrafluoroethylene grafts and blood vessels were achieved using absorbable cuff material in experimental and clinical studies. The cuff was made of a synthetic biodegradable material, a lactic-glycolic acid copolymer, similar in composition to conventional absorbable surgical sutures. METHODS: In the experimental study, vascular anastomoses for prosthetic interposition of the infrarenal aorta in rabbits were created using the cuff method. Six months after surgery, the cuff anastomoses sites were examined angiographically and microscopically and found to be patent and smooth without neointimal hyperplasia. RESULTS: The cuff layer had been completely absorbed. The clinical application used a similar technique and involved the creation of forearm bridge graft fistula in twelve patients for hemodialysis. In eight patients, Doppler fistula flow rate ranged from 167 ml/min to 392 ml/min. Ten of the twelve patients continued dialysis uneventfully. The one-year patency rate was 78% (7/9). The longest patency period was 920 days and the graft access continued to maintain sufficient blood flow for hemodialysis. CONCLUSIONS: This absorbable cuff material is therefore well suited for the construction of prosthetic vascular end-to-end anastomoses.     

A double bifurcated graft for abdominal aorta and bilateral iliac artery reconstruction

Revascularization of the hypogastric artery often tends to be neglected in aortoiliac reconstructive surgery; however, its incomplete revascularization can result in unfavorable complications such as buttock claudication or necrosis, vascular impotence, and colonic ischemia. Multiple vascular lesions in the abdominal aorta and bilateral iliac arteries were reconstructed using a newly designed double bifurcated graft in five male patients. All five patients demonstrated excellent graft limb patency and postoperative improvement of the ankle-brachial pressure index without any clinical signs of ischemia in regions of the hypogastric artery. Thus, we conclude that an aggressive approach toward hypogastric circulation maintenance is essential in aortoiliac reconstructive surgery. By using this double bifurcated graft, rapid and safe revascularization of the bilateral hypogastric arteries concomitant with the external iliac or femoral arteries can be performed.     

Micro-mainframe-link Personal Clinical Research System

We constructed a micro-mainframe-link clinical research system for personal use (Personal Clinical Research System). This system was developed with both a mainframe computer and a personal computer (PC). The prepared programs included a database manager (on the mainframe computer), a user interface program (on the PC), and a communication control program that connected the mainframe computer with the PC. The database on the mainframe computer was constructed by two methods. The first method was to transmit data from the PC to the mainframe computer. The second method was to extract data from the patient information database. Using this system, a physician is able to construct a personal research database that contains interesting data for the physician. In addition, the physician is able to accumulate data on a special field using this system. A discharge summary system is now in operation as an example of this system.     

Ostreopsis sp., a possible origin of palytoxin (PTX) in parrotfish Scarus ovifrons.

A clone of toxic dinoflagellate Ostreopsis sp. and six specimens of a parrotfish Scarus ovifrons were collected in October 1997 at Tokushima Prefecture, Japan. Ostreopsis sp. was cultured in ESM medium for 16 days, and after rearing the cell pellet (about 4.0x10(5) cells) was extracted with 50% methanol, partitioned between an aqueous layer and 1-butanol layer, and biochemically tested. Similarly, the crude toxin from S. ovifrons was extracted, and tested. The mice injected with each 1-butanol layer from Ostreopsis sp. and S. ovifrons showed the common symptoms of convulsion, drowsiness and collapse, and died within 48 h. The lethal potency of Ostreopsis sp. was calculated to be 1.0x10(-4) MU/cell. All specimens of S. ovifrons were found to be toxic, where the highest potency was determined as 2 MU/g in muscle of one specimen. After being injected with toxins, the serum creatine phosphokinase levels of mice were found to be elevated. Toxins from Ostreopsis sp. and S. ovifrons showed delayed haemolytic activity with mouse and human erythrocytes, which was inhibited by an anti-palytoxin (PTX) antibody antibody and ouabain. Toxins from Ostreopsis sp. and S. ovifrons thus resembled each other, and strongly suggested to be PTX or its akin substance. Additionally, a considerable number of adherent Ostreopsis sp. was found in the gut contents of S. ovifrons during the heavy occurrence of Ostreopsis sp. in October 1997 at Tokushima Prefecture. From the above results, it can be strongly postulated that the dinoflagellate Ostreopsis sp. is the origin of PTX which is sequestered by the parrotfish S. ovifrons through food chain.     

Suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the high-affinity antibody response in C57BL/6 mice.

In the humoral immune response to an invasion of foreign antigens, B cells differentiate into low-affinity antibody-forming cells (AFCs) that mainly secrete IgM or, through germinal center (GC) formation, into high-affinity AFCs that secrete IgG-class antibodies with a higher affinity for the antigen. Previous studies have established the suppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on low-affinity antibody responses to antigens. However, whether and how TCDD affects the high-affinity antibody response to antigens has not yet been clarified. In this paper we investigate the effects of TCDD on GC formation, high-affinity AFC generation, and high-affinity antibody production in the primary humoral immune response. C57BL/6 mice were orally administered 0 or 20 microg/kg of TCDD and subsequently immunized with alum-precipitated ovalbumin (OVA) on day 0. Then the GC formation in the spleen and OVA-specific antibodies in the plasma, was evaluated until day 14 postimmunization. TCDD exposure reduced the production of OVA-specific IgG1 on days 10 and 14. GC formation in the spleen was also suppressed by TCDD exposure, and the suppression persisted from day 7 until day 14. In TCDD-administered mice, on day 7, cellular proliferation in the GCs was significantly suppressed, although apoptosis was not markedly affected. In order to measure high-affinity antibody and high-affinity AFCs, the mice were administered TCDD followed by immunization with alum-precipitated (4-hydroxy-3-nitrophenyl) acetyl linked to chicken gamma-globulin (NP-CG). The frequency of high-affinity NP-specific AFCs that bind to low-haptenated antigen was clearly shown to be reduced in the spleen on days 10 and 14. Furthermore, the high-affinity anti-NP IgG1 levels on days 10 and 14 postimmunization were significantly reduced by TCDD exposure. Taken together, the results of this paper demonstrate that TCDD exposure inhibits the generation of high-affinity AFCs and high-affinity antibody production during the primary humoral immune response and suggest that these alterations were caused by the suppression of antigen-responding B-cell proliferation induced by TCDD during GC formation.     

Management of soft tissue sarcomas (STS) in first isolated local recurrence: a retrospective study of 83 cases.

PURPOSE: To analyze the management and clinical outcome of patients treated for a first isolated local recurrence of soft tissue sarcomas (trunk or extremities) and to identify prognosis factors. METHODS AND MATERIAL: Between 1980 and 1999, 83 adult patients were included in the study. Mean age was 61 years. Mean tumor size was 6 cm. Most sarcomas were located in extremities (n=74), were deep (n=60), and proximal (n=53); 30 involved nerves or vessels. Histologic subtypes were mainly grade 2 (42%) or 3 (36%) histiocytofibrosarcomas (49%) and liposarcomas (20%). Surgical treatment of recurrences consisted in wide excision (29 cases), marginal resection (43 cases), 5 patients requiring amputation. Final results were R0 (n=33), R1 (n=47) or R2 (n=3) resection. Besides surgery, 6 patients received neo-adjuvant and 7 others adjuvant chemotherapy. Twenty three patients received post-operative external beam radiotherapy (EBRT) (mean dose 55 Gy) and 26 interstitial 192Ir low dose rate brachytherapy (BCT) (mean dose 45 Gy for BCT alone, 22 Gy when associated with EBRT), 19 patients being re-irradiated. RESULTS: Mean follow up was 13 years. Thirty-seven (45%) patients relapsed, 62% of whom presenting an isolated local recurrence. Nineteen patients developed distant metastases. Multivariate analysis showed only tumor depth (P=0.05) and re-resection for primary R1 resection (P=0.018) being independent prognosis factors for tumor control, radiotherapy (EBRT and/or BCT) being significant in univariate analysis (P=0.05). Overall survival rate was 73%, 54%, and 47% at, respectively, 3.5 and 10 years, and was 65%, 35% and 32% after a further local recurrence. Multivariate analysis showed trunk (P=0.0001) or inferior extremity locations (P=0.023), symptomatic (P=0.001), high grade (P=0.01), deep (P=0.01) tumors, and the occurrence of a further local failure (P=0.004) as unfavorable characteristics for overall survival. CONCLUSIONS: A first isolated local recurrence of STS increases mainly the risk of a subsequent local relapse. Quality of local treatment is decisive. When a conservative treatment is feasible, it should combine surgical resection and radiotherapy, BCT being the best suited in previously irradiated patients. Efforts have to be pursued to increase quality of the treatment of primary tumors, at best performed in centers that have expertise in this field.     

Malignant phyllodes tumor of the breast with hypoglycemia: report of a case

A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.