Mixed endocrine tumors

Mixed endocrine tumors are tumors composed of at least two distinct tumor populations, one of which is endocrine. Because of their rarity and unusual presentation, endocrine mixed tumors raise many problems of diagnosis, management and therapy. Three main types of endocrine mixed tumors are recognized: The existence of these various types has been confirmed by recent molecular studies, even if the same studies have also shown that the histogenesis of a mixed endocrine tumor cannot be predicted from its histological features. Composite tumors are the less rare mixed tumors. The recent WHO classification recommends to restrict the term of composite endocrine tumor to the epithelial tumors containing at least 30% of obviously tumoral endocrine cells; some authors recommend to use higher thresholds, of at least 50%, in order to avoid overdiagnosis. The endocrine component is usually well differentiated, easily identified by its suggestive histological features; the endocrine nature of tumor cells is confirmed by the immunodetection of specific endocrine and neuro-endocrine markers (such as chromogranin A and synaptophysin). In some cases, the endocrine component is poorly differentiated: the demonstration of neuro-endocrine markers is necessary to confirm the diagnosis. Mixed tumors can occur in every anatomical site; they are more frequent in organs containing endocrine cells in the normal state (especially the digestive tract and the pancreas), but they can also be observed in organs devoid of endocrine cells (such as the mammary gland). The management of mixed endocrine tumors must take into account the more aggressive component. Mixed tumors containing a well differentiated endocrine component and an adenocarcinomatous component are to be treated like adenocarcinomas. Mixed tumors containing a poorly differentiated endocrine component must be considered as poorly differentiated endocrine carcinomas.     

Ocular pharmacokinetics of fluocinolone acetonide after Retisert intravitreal implantation in rabbits over a 1-year period.

PURPOSE: The present study was designed to examine the pharmacokinetics of a fluocinolone acetonide (FA) intravitreal implant in pigmented rabbits. METHODS: Pigmented rabbits were randomly assigned to receive either a 0.5 mg or 2.0 mg FA intravitreal implant (Retisert). Four animals were sacrificed per time point (2 hours; 2 weeks; and 3, 6, 9, and 12 months after implantation) for FA intraocular levels determination. RESULTS: In the vitreous, concentration of FA was relatively constant from the first time point, 2 hours, through 1 year, and dose-related, approximately seven- to eight-fold greater in the 2-mg implant. Concentrations of FA were generally higher in the vitreous (11-18 and 75-146 ng/g) and retina (42-87 and 224-489 ng/g) than in the aqueous humor (0.21-1.1 and 2.6-13.0 ng/g) for the 0.5- and 2-mg implants, respectively. Urine and plasma values were below the lower limit of quantitation (200 pg/mL) for all observations, indicating no evidence of systemic absorption. CONCLUSIONS: In this rabbit study, the Retisert provides relatively constant levels of FA in the posterior pole, which is consistent with previous reports of its clinical utility.     

Phase I combining a P-glycoprotein inhibitor, MS209, in combination with docetaxel in patients with advanced malignancies.

PURPOSE: The purpose of this study was to investigate the safety and tolerability of MS209, a potent inhibitor of P-glycoprotein, when given in combination with docetaxel and to determine whether MS209 affects docetaxel pharmacokinetics. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies were eligible for this phase I trial. Docetaxel as 1-hour infusion was given alone during the first cycle. MS209 was introduced as of cycle 2 and given orally 30 minutes after docetaxel infusion. The dose escalation scheme followed a modified Fibonacci model with six steps (docetaxel, 60-100 mg/m2 and MS209, 300-1,200 mg per body). RESULTS: A total of 30 patients were treated at five dose levels. Dose-limiting toxicities were febrile neutropenia, infection, stomatitis, dysphagia, and fatigue. The maximum tolerated dose was reached at level 5 (docetaxel, 80-MS: 1,200). Pharmacokinetic analysis failed to show a strong pharmacokinetic interaction between the two compounds, but at the highest dose levels, there is a trend to an increase of docetaxel AUC when this agent is given in combination with MS209. CONCLUSION: MS209 can be given in combination with docetaxel, with limited effect on docetaxel toxicity or pharmacokinetics.     

Management of phyllodes breast tumors

Phyllodes tumors are a rare distinctive fibroepithelial tumors of the breast and their management continues to be questioned. The aim of our study was to examine the treatment and outcome of 165 patients with phyllodes tumors and to review the options for surgical management. This is a retrospective study of 165 patients who presented to the Institut Curie between January 1994 and November 2008 for benign, borderline or malignant phyllodes tumors. The median follow-up was 12.65 months [range 0-149.8]. The median age at diagnosis was 44 years [range 17-79]. One hundred and sixty patients (97%) had breast-conserving treatment, of whom 3 patients (1.8%) had oncoplastic breast surgery. Younger women had a significantly higher chance of having a benign phyllodes tumor (p = 0.0001) or a tumor of small size (p < 0.0001). Histologic examination showed 114 benign (69%), 37 borderline (22%) and 14 malignant tumors (9%). The median tumor size was 30 mm [range 5-150]. The tumor margins were considered incomplete (< 10 mm) in 46 out of 165 cases (28%) with 52% revision surgery. Only the tumor grade was a significant risk factor for incomplete tumor margins (p = 0.005). Fifteen patients developed local recurrence (10%) and two, metastases. In univariate analysis, the histologic grade (p = 0.008), and tumor size (p = 0.02) were significative risk factors for local recurrence with an accentuated risk for "borderline" tumors and tumors of large size.).Similar results were obtained using multivariate analysis (p = 0.07). The mainstay of treatment for phyllodes tumors remains excision with a safe surgical margin, taking advantage breast conserving surgery where amenable. For borderline or malignant phyllodes tumors or in cases of local tumor recurrence, mastectomy, and immediate breast reconstruction may become the preferred option. Genetic analysis will potentially supplement classical histologic examination in order to improve our management of these tumors. The role of adjuvant treatments is unproven and must be considered on a case-by-case basis.     

Early mechanical failure in total knee arthroplasty

Early mechanical dysfunction of a total knee arthroplasty (TKA) is a challenging problem in terms of causality and solutions. The current strategy in our department is to perform a complete TKA revision rather than the less invasive partial procedures when a clear mechanical cause of failure has been found. In this investigation, we assessed 21 patients who underwent complete TKA revision in 2003-2004 in our institution within the first two years following the index TKA. Various clinical presentations included pain, stiffness, instability, and femoro-patellar signs. These corresponded to implant size, position, and fixation issues. The IKS knee score/function significantly increased from 47/47 to 85/78 at follow-up (six months minimum). Compared to the data in the literature, this systematic full revision seems to be a reasonable approach. This attitude takes advantage of the modularity of the implants for allowing perioperative adjustments of position, fixation, and constraint. Based on the results of our study, we propose a list of six mechanical pitfalls to be evaluated in the case of early dysfunction: frontal misalignment, sagittal overstuffing or malpositioning, axial malrotation, poor bone fixation, inappropriate constraint or ligamentous balance, and inappropriate level of the joint space.     

Cryopreserved iliac artery allograft for primary arterial revascularization in adult liver transplantation

Arterial allograft represents a material of choice for primary arterial revascularization in liver transplantation (LT) when interposition of a vascular conduit is required. In case of non-availability of such graft, the use of cryopreserved vessels should be an interesting option. Three patients were grafted using a cryopreserved iliac artery allograft (CIAA) previously harvested and stored at -140°C in a tissue bank. An auxiliary partial LT was performed in one patient for acute liver failure. During follow-up, an efficient regeneration of the native hemi-liver was observed while atrophy of the auxiliary graft occurred, leading to functional portal vein and hepatic artery thrombosis at six and nine months, respectively. Two other patients presented with celiac trunk compression because of arcuate ligament without available arterial allograft in the donor. Late arterial thrombosis occurred at six months in one patient without impairment of graft function. The last patient was alive and symptom free 29 months after LT with a patent cryopreserved arterial conduit. Our preliminary results suggest that CIAA might represent an efficient solution as vessel interposition for primary arterial hepatic revascularization in LT setting when no other suitable graft is available. However, long-term patency of CIAA remains questionable.     

Screw impingement on the extensor tendons in distal radius fractures treated by volar plating: sonographic appearance

OBJECTIVE: The objective of our study was to analyze the sonography examinations of nine consecutive patients with a history of distal radius fracture treated by open reduction and internal fixation of the volar plate who were referred by hand surgeons for sonography of the dorsal aspect of the wrist. CONCLUSION: We postulate that impingement of the extensor tendons in patients with distal radius fracture treated by volar plating starts with local hyperemia and is followed by tenosynovitis and, finally, by partial and complete tendon tears. Sonography is an effective, dynamic, and noninvasive technique with which to diagnose and evaluate damage to the extensor tendons and their synovial sheaths.     

Strontium ranelate: New data on fracture prevention and mechanisms of action

Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile that optimizes therapeutic adherence. Strontium ranelate is the first compound to simultaneously decrease bone resorption and stimulate bone formation. Its anti-fracture efficacy at various skeletal sites has been established for as long as 5 years through studies of the highest methodological standards. Increases in bone mineral density observed after 1 year of treatment are predictive of the long-term fracture efficacy, suggesting for the first time in osteoporosis that bone densitometry can be used as a monitoring tool. Due to a positive risk/benefit ratio, strontium ranelate is now considered as a first-line treatment in the management of osteoporosis.     

Patient-based decision for resuming activity after ACL reconstruction: a single-centre experience

Purpose

The purpose of the study was to report the functional outcome following anterior cruciate ligament (ACL) reconstruction in patients who decide when to resume work and normal sporting activity post-operatively. The hypothesis tested was that patient-based decision to return to work and sport was possible without compromising functional outcome and increased the rate of repeat rupture in comparison with the existing literature.

Methods

This was a monocentric, retrospective study. Seventy-two patients requiring primary ACL reconstruction were included. All patients were followed up for a mean period of 4.3 years. Return to work and to sporting activity was allowed based on patient’s decision. No restriction was suggested by the physician. Delays to return to work and sports and occurrence of graft failure were documented.

Results

Sixty-six patients (92 %) returned to any sporting activity. The mean delay was 4.1 months for running, 6.1 months for pivoting sports, and 6.6 months for contact sports. Return to competitive sport was possible in 82 % of patients after a mean delay of 7.1 months. Return to work was possible for 96 % of patients after a mean delay of 2.3 months. Index Tegner score normalized in 71 % of patients. Four repeat ruptures (6 %) were observed, all of them following a significant knee injury.

Conclusions

Patient-based decision to return to work and sport was possible without compromising functional outcome. The post-operative restrictions implemented by orthopaedic surgeons following ACL reconstructions may be relaxed and more patient based.

     

Synergistic inhibitory effect of high-intensity focused ultrasound combined with chemotherapy on Dunning adenocarcinoma

OBJECTIVE: To evaluate the therapeutic effect of high-intensity focused ultrasound (HIFU) combined with chemotherapy (paclitaxel + estramustine) on AT2 Dunning adenocarcinoma, as no satisfactory treatment for localized prostate cancer is available for patients with a poor prognosis, e.g. stage T3, a high Gleason score, or a prostate-specific antigen level of >15 ng/mL. MATERIALS AND METHODS: Forty-one Dunning AT2 tumour-bearing Copenhagen rats were divided into four groups, i.e. control, chemotherapy, HIFU, and chemotherapy + HIFU (the last three treated for 1 week). The growth in tumour volume was recorded for 3 weeks, the point at which tumour volume was considered to have doubled (doubling time). The growth curves of each group were plotted and evaluated statistically. RESULTS: At 30 days of follow-up the distributions of tumour volume with treatment group were significantly different (P < 0.001); volumes were significantly greater in the control than in the chemotherapy-only or in the HIFU-only group (both P = 0.006). The greatest difference was between the chemotherapy + HIFU and the control group. The tumour doubling times were 13.2 days for HIFU-only, 31.2 days for chemotherapy + HIFU and 7.7 days for the controls. CONCLUSION: These results suggest that this combined therapy could be useful for treating patients with high-risk prostate cancer.