Long-term patency of multiple lymphatic-venous anastomoses in cancer-related lymphedema: A single center observational study.

OBJECTIVES: Lymphedema is always initially treated by combined decongestive physiotherapy (CDP). Those cases, refractory to CDP, may be managed by surgical therapy. One of the most used microsurgical procedures is represented by the technique of lymphatic-venous anastomosis (LVA). But very few papers report long term results of LVA. The aim of this study is to assess the long-term patency of multiple lymphatic-venous anastomosis (MLVA) for the treatment of secondary lymphedemas. METHODS: From January 2014 to December 2014, 101 patients (mean age: 56.94 ± 8.98 years; female/male: 86/15) affected by secondary cancer-related lymphedema (38 lower and 63 upper limbs) were treated by MLVA. All lymphedemas had previously been treated by conservative therapy without sustained results. Many patients (78%) had 1-3 episodes of acute lymphangitis/year. Lymphoscintigraphy, venous duplex-ultrasonography, and abdominal or axillary ultrasound investigation were performed preoperatively. MLVA patency was assessed by the lymphatic transport index (LyTI) and lymphoscintigraphic pattern. RESULTS: At 1 year after surgery, excess volume reduction was 75%-90% in the early stage II secondary lymphedemas, and 60%-75% in the late stage II. The decrease in volume maintained stability in the 5-years follow-up period. Two more advanced lower and one upper limb lymphedemas had 45%-60% reduction. LyTI showed a significant decrease between the preoperative mean value (31.7 ± 9.43) and after 18 months from surgery (11.2 ± 1.91) (p < .001). MLVA patency was shown in 98 (97%) patients. No patients had evidence of postoperative lymphangitis. CONCLUSIONS: This study demonstrated the long-term patency of MLVA in the treatment of cancer-related lymphedemas.

In-111 octreotide SPECT/CT in the early diagnosis of pulmonary sarcoidosis: A case report.

Sarcoidosis is a granulomatous disease of unknown etiology. At present the best diagnostic imaging procedure to assess stage and activity of sarcoidosis is controversial. We report the case of a 50-year-old male admitted with a history of dyspnea and fatigue with past medical history negative for smoking, occupational and environmental risk factors. Physical examination, routine blood tests, and pulmonary function tests were normal except for hypercalciuria. A chest radiograph showed bilateral hilar lymphadenopathy. Single photon emission computed tomography and/or computed tomography (SPECT and/or CT) In-111 Octreotide (Octreoscan) scintigraphy confirmed morphologic involvement of bilateral hilar lymph nodes and a mediastinoscopy biopsy specimen provided diagnosis of pulmonary sarcoidosis (stage 0). This clinical case shows the effectiveness of In-111 Octreotide SPECT and/or CT in the early diagnosis of pulmonary sarcoidosis.

Lymphoscintigraphy for the evaluation of limb lymphatic flow disorders: Report of technical procedural standards from an Italian Nuclear Medicine expert panel. / Linfogammagrafía para la evaluación de trastornos del flujo linfático de las extremidades: informe de estándares de procedimientos técnicos de un panel de expertos de medicina nuclear italiano.

Lymphoscintigraphy represents the "gold standard" for diagnosis of lymphedema, but an important limitation is the lack of procedural standardization. The aim of this Italian expert panel was to provide a procedural standard for lymphoscintigraphy in the evaluation of lymphatic system disorders. Topic anaesthetic gels containing lidocaine should be avoided. Patients should remove compressive dressings. Total recommended activity for 99mTc-nanocolloid administration in adults is 74MBq, or 37MBq per limb and per investigated compartment, in single or multiple aliquots. 2-3 subcutaneous injections should be performed (II-III±I interdigital space of each hand/foot), avoiding intravascular injection. Deep lymphatic system of lower limbs should be evaluated in presence of dermal back-flow or lymphatic stasis (1-2 subfascial administrations in retro-malleolar or plantar region). Planar images should be acquired from injection site to liver with whole-body or serial static acquisitions 20' and 90' after subcutaneous administration. Additional information on lymphatic pathways is obtained after a quick and/or prolonged exercise protocol. SPECT/CT is recommended to study the thoracic, abdominal and pelvic territories. When required, deep lymphatic system of lower limbs should be evaluated with static acquisition 90' after subfascial administration. The report should describe administration and imaging procedure, exercise protocol, qualitative and semi-quantitative analysis (wash-out rate, transport index), potential sources of error. Due to the essential role fulfilled by lymphoscintigraphy in clinical management of primary and secondary lymphedema, an effort for the standardization of this technique should be made to provide the clinicians with a homogeneous and reliable technical methodology.

Rationale for Study of the Deep Subfascial Lymphatic Vessels During Lymphoscintigraphy for the Diagnosis of Peripheral Lymphedema.

PURPOSE: The current study aimed to determine the utility of including the study of deep subfascial lymphatic vessels in a 2-compartment lymphoscintigraphy for the diagnosis of lymphedema in patients with limb swelling. Lymphoscintigraphy is a valuable imaging tool for the timely diagnosis of peripheral lymphedema. However, there is a lack of standardization in its application, especially regarding which type of lymphatic vessels to examine (superficial, deep, or both). METHODS: Two hundred fifty-eight patients with lymphedema underwent segmental lymphoscintigraphy. The transport index (TI) was calculated to categorize the flow of the superficial and deep vessels as normal (<10) or pathological (≥10). The scores from 248 patients (48 unilateral arm, 86 unilateral leg, 114 bilateral leg) were tested with a 3-way analysis of variance to examine the relationship between affected limb, deep or superficial pathways, and primary or secondary lymphedema. The relationship between clinical presentation and TI was also investigated. RESULTS: In general, primary and secondary lymphedema patients had similar patterns of lymphoscintigraphic lymphatic abnormalities. Patients with unilateral clinical presentation can have bilateral TI abnormalities. The vast majority of patients (88%-98%) had either the deep subfascial vessels alone, or both the superficial and deep vessels, with a pathological TI. CONCLUSIONS: A 2-compartment lymphoscintigraphy is able to accurately detect lymphatic flow abnormalities in patients with limb swelling. Given that the vast majority of patients had deep lymphatic vessels abnormalities, inclusion of these vessels in the lymphoscintigraphic diagnostic protocol is recommended.

Prevention of systemic toxicity in hyperthermic isolated lung perfusion using radioisotopic leakage monitoring.

RATIONALE: Hyperthermic isolated lung Perfusion (ILuP) is used to deliver high-dose chemotherapy to pulmonary metastases while sparing systemic toxicity. Accurate leakage monitoring is however necessary. This study aimed to verify the accuracy of radionuclide leakage monitoring in patients undergoing ILuP, by comparing this method with serial blood sampling. METHODS: A total of 15 consecutive ILuP procedures were performed on eleven patients affected by lung metastases from soft tissue sarcoma. After establishing isolated perfusion, erythrocytes of systemic blood (SB) were labelled with 0.2 MBq/kg of 99mTc. The baseline SB counting rate (CR) was assessed using a γ-probe. Subsequently, erythrocytes of the circuit blood (CB) were labelled with 2 Mbq/kg of 99mTc. Radioactivity leakage factor (RLF) was continuously measured using a formula, accounting for CR, systemic/circuit activity ratio and total/systemic volume ratio. The TNF-α concentration in SB and CB was measured by enzymelinked immunosorbent assay (ELISA) throughout the procedure. RESULTS: RLF averaged 2.3 ± 1.5%, while the systemic/circuit TNF-α ratio was 0.05 ± 0.12%. These two indices were strictly correlated in all of the procedures (average Rvalue 0.88 ± 0.07). RLF exceeded 5% during three of 15 procedures, prompting the application of compensatory manoeuvres. ELISA confirmed a marked increase in systemic TNF-α levels in these patients (2.6 ± 3.5 ng/ml). Conversely, patients whose RLF did not exceed the 5% threshold presented a mean TNF-α of 0.02 ± 0.005 ng/ml (p < 0.01). CONCLUSIONS: In patients submitted to ILuP, RLF monitoring is feasible and accurate. Moreover, it grants immediate results, permitting for the adoption of corrective manoeuvres for leakage, thus minimising toxicity.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema.

BACKGROUND: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema. METHODS: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein. RESULTS: The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer. CONCLUSIONS: The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs.

The role of sentinel lymph node biopsy in patients with local recurrence or in-transit metastasis of melanoma.

From January 2003 to March 2010, a prospective study was undertaken at the National Cancer Research Institute of Genoa in 15 patients with melanoma who had local recurrence (LR) or a few (≤ 3) in-transit metastases and clinically-negative regional lymph nodes with the aim of defining: i) the feasibility of sentinel node re-staging (r-sN) of the regional nodal basin; ii) the prognostic value of sentinel node status, and iii) the potential benefit in terms of disease-free survival and overall survival in patients with an histologically-positive sentinel node undergoing therapeutic regional lymph node dissection. Preoperative lymphoscintigraphy was performed to identify the r-sN: the radiotracer was intra-dermally injected around the LR or in-transit metastasis. Moreover, 10 min prior to the operative procedure, 0.5 ml intradermal injection of Patent-Blue-V dye was given around each LR or in-transit metastasis site, so that r-sN identification was achieved by both visualization of the nodal blue dye staining and the information supplied by gamma-detection probe. At least one sentinel node was intra-operatively identified in each patient, and a tumor-positive r-sN was required in four out of fifteen patients. The interval between the diagnosis of primary melanoma and the onset of recurrence was longer, although not significantly, in patients with tumor-negative r-sN, a compared to tumor-positive r-sN (49 ± 47 months vs. 25 ± 19 months, p=0.342). There was a trend toward an improved 1-, 3-, and 5-year disease-free survival and overall survival in patients with tumor-negative r-sN a compared to tumor-positive r-sN. Hence, the r-sN proved to be a feasible and accurate staging procedure even in patients with a few localizations of LR or in-transit metastases (≤ 3). r-sN identified those with a more favorable prognosis, supporting an aggressive therapeutic approach in the natural history of their disease; moreover, an unnecessary regional lymph node dissection was safely avoided in 11 out of 15 73.3% patients because they had a tumor-negative r-sN.

Efficacy and safety of once-monthly continuous erythropoietin receptor activator in patients with chronic renal anemia.

BACKGROUND: In the management of anemia in patients with chronic kidney disease stage 5 undergoing dialysis (CKD-5D), maintaining hemoglobin (Hb) within the range recommended by the guidelines is challenging. METHODS: The CARISMA study aim was to evaluate the efficacy, safety and tolerability of a once-monthly continuous erythropoietin receptor activator (CERA) for the treatment of anemia in CKD-5D patients. In this single-arm, multicenter, open-label, phase IIIb study, we screened adult patients from 66 centers in Italy receiving intravenous epoetin alfa or beta or darbepoetin alfa. Eligible patients entered the CERA dose titration phase (DTP), followed by an efficacy evaluation period (EEP) and a long-term safety period (LTSP). Patients were analyzed by intention-to-treat (ITT), per protocol (PP) and safety populations. RESULTS: The rate of patients maintaining Hb within the range 10.0-12.0 g/dL throughout the EEP was 63.22% (220/348), and concentration from baseline to any postbaseline time point. CERA may thus offer a convenient and effective treatment 73.94% (122/165) in the ITT and PP population, respectively, periods in both populations. The rate of patients requiring a dose change was higher during the DTP (69.2%) and the LTSP (73.0%) than during the EEP (54.5%), as expected. CERA treatment was generally well tolerated. CONCLUSIONS: Once-monthly CERA administered to CKD-5D patients was associated with negligible changes in mean Hb option for these patients.

Benefit of doxycycline treatment on articular disability caused by dialysis related amyloidosis.

Abstract Doxycycline inhibits amyloid formation in vitro and its therapeutic efficacy is under evaluation in clinical trials for different protein conformational diseases, including prion diseases, Alzheimer's disease and transthyretin amyloidosis. In patients on chronic hemodialysis, a persistently high concentration of ß2-microglobulin causes a form of amyloidosis (dialysis-related amyloidosis, DRA) localized in bones and ligaments. Since doxycycline inhibits ß2-microglobulin fibrillogenesis in vitro and accumulates in bones, DRA represents an ideal form of amyloidosis where doxycycline may reach a therapeutic concentration at the site of amyloid deposition. Three patients on long-term dialysis with severe articular impairment and uncontrollable pain due to DRA were treated with 100 mg of doxycycline daily. Pharmacokinetics and safety of treatment were conducted. Plasmatic levels of the drug reached a plateau after one week (1.1-2.3 µg/ml). Treatment was well tolerated in two patients for a year, while one was suspended after 5 months due to mild esophagitis. Treatment was associated with a significant reduction in articular pain and with a significant and measurable improvement in passive and active movements in all cases, despite the persistence of unchanged amyloid deposits measured by magnetic resonance imaging.

Lymphatic microsurgery to treat lymphedema: techniques and indications for better results.

This study aimed to report new clinical approaches to the treatment of lymphatic disorders by microsurgical techniques based on histological and immunohistochemical findings. The authors' wide clinical experience in the treatment of patients with peripheral lymphedema by microsurgical techniques is reported. Microsurgical methods included derivative lymphatic-venous anastomoses and lymphatic reconstruction by interpositioned vein grafted shunts. In all patients, lymphatic and lymph nodal tissues were sent for histological assessment, together with specimen of the interstitial matrix. Diagnostic investigations consisted in venous duplex scan and lymphoscintigraphy. Results were assessed clinically by volumetry performed preoperatively and postoperatively at 3 to 6 months and at 1, 3, and 5 years. The outcome obtained in treating lymphedemas at different stages was analyzed for volume reduction, stability of results with time, reduction of dermatolymphangioadenitis attacks, necessity of wearing elastic supports, and use of conservative measures postoperatively. Microsurgical lymphatic derivative and reconstructive techniques allow bringing about positive results in the treatment of peripheral lymphedema, above all in early stages when tissular changes are slight and allow almost a complete restore of lymphatic drainage.

Lymphedema microsurgical preventive healing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer.

OBJECTIVE: Lower limb lymphedema (LLL) is the most disabling adverse effect of surgical treatment of vulvar cancer. This study describes the use of microsurgical lymphatic venous anastomosis (LVA) to prevent LLL in patients with vulvar cancer undergoing inguinofemoral lymph node dissection (ILND). METHODS: The study included 8 patients with invasive carcinoma of the vulva who underwent unilateral or bilateral ILND. Before incision of the skin in the inguinal region, blue dye was injected in the thigh muscles to identify the lymphatic vessels draining the leg. Lymphatic venous anastomosis was performed by inserting the blue lymphatics coming from the lower limb into one of the collateral branches of the femoral vein (telescopic end-to-end anastomosis). An historical control group of 7 patients, which underwent ILND without LVA, was used as comparison. After 1 month from the surgery, all patients underwent a lymphoscintigraphy. RESULTS: In the study group, 4 patients underwent bilateral ILND, and 4 patients underwent unilateral ILND. Blue-dyed lymphatics and nodes were identified in all patients. It was possible to perform LVA in all the patients. The mean (SD) time required to perform a monolateral LVA was 23.1 (3.6) minutes (range, 17-32 minutes). The mean (SD) follow-up was 16.7 (6.2) months; there was only 1 case of grade 1 lymphedema of the right leg. Lymphoscintigraphic results showed a total mean transport index were 9.08 and 14.54 in the study and the control groups, respectively (P = 0.092). CONCLUSIONS: This study shows for the first time the feasibility of LVA in patients with vulvar cancer undergoing ILND. Future studies including larger series of patients should clarify whether this microsurgical technique reduces the incidence of LLL after ILND.

Time savings associated with C.E.R.A. once monthly: a time-and-motion study in hemodialysis centers in five European countries.

OBJECTIVE: This time-and-motion study aimed to quantify healthcare personnel time associated with routine anemia-management tasks for maintenance therapy with C.E.R.A. (continuous erythropoietin receptor activator) that treats anemia with once-monthly injections versus other erythropoiesis-stimulating agents ('Other ESAs'), including shorter-acting ESAs (epoetin alfa, epeotin beta) and darbepoetin alfa. METHODS AND DESIGN: This was a non-interventional, observational study where patients were treated for anemia according to individual center practices. Time taken to complete frequent anemia-management tasks for both groups (C.E.R.A. vs. 'Other ESAs') was recorded and potential annual time savings per patient and per center following assumed 100% uptake of C.E.R.A. once monthly were estimated. RESULTS: For 'Other ESAs', the average total time spent per patient per year on frequent anemia management-related tasks ranged from 48 minutes in Spain to 265 minutes in Poland. For C.E.R.A. once monthly, the average total time spent per patient per year ranged from 12 minutes in Spain to 39 minutes in Poland, a reduction in actual time spent of 76-89% versus 'Other ESAs'. 100% adoption of C.E.R.A. once monthly may result in average annual time savings of 26-553 hours, a reduction of 67-95% depending on center size and frequency distribution of 'Other ESAs'. LIMITATIONS: Due to variability in treatment practices between centers (differences in task, description and frequency distribution of 'Other ESAs') and the small numbers of centers participating in each country, it is difficult to generalize annual per patient time results to reflect each country. Per center results should be interpreted with caution as they were derived based on specific center sizes that may not reflect typical center sizes in the country. CONCLUSIONS: Adoption of C.E.R.A. once monthly could offer substantial time savings on frequent anemia management-related tasks versus 'Other ESAs'; allowing re-allocation of scarce resources to other aspects of patient care.

Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial.

BACKGROUND: Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes. METHODS: Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients). RESULTS: CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta(2) 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta(2) 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170). CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

[Erythropoiesis-stimulating agents: from the origins to new challenges]. / Gli agenti stimolanti l'eritropoiesi: dalle origini alle nuove sfide - le indicazioni degli studi clinici.

The structure, pharmacodynamics and pharmacokinetics of erythropoiesis-stimulating agents (ESAs) have changed from the first (rHuEPO) to the second (darbepoetin) and third generations (CERA), with an increase in glycosylated groups accompanied by a reduction of the affinity for the receptor and an increased half-life. After the initial success resulting from the correction of anemia, large observational trials have shown an increase in mortality related to higher hemoglobin values in kidney patients. Subsequent analysis of the trial results revealed that the cause of the worse outcomes was not the hemoglobin level but the high ESA dose. Resistance to ESAs resulting in their increased consumption is hepcidin mediated, as the hormone is upregulated by inflammatory factors and by a drop in the ESA level below the physiological erythropoietic threshold. This is where the ESA kinetics comes into play. Analysis of different databases has shown that the variability of hemoglobin levels over time caused outcomes to worsen and was correlated with frequent changes in the ESA dose. Many studies have demonstrated that third-generation ESAs ensure greater stability and physiological action, allowing to reduce dose changes and overshooting to a minimum.

Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial.

BACKGROUND: Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly. METHODS: Haemodialysis patients (n = 490) on stable once-weekly intravenous darbepoetin alfa were randomized to methoxy polyethylene glycol-epoetin beta once monthly or darbepoetin alfa every 2 weeks for 26 weeks, with dose adjustment for individual haemoglobin target (11-13 g/dL; maximum decrease from baseline 1 g/dL). Subsequently, patients entered a second 26-week period of once-monthly methoxy polyethylene glycol-epoetin beta and darbepoetin alfa. The primary endpoint was the proportion of patients who maintained average haemoglobin ≥10.5 g/dL, with a decrease from baseline ≤1 g/dL, in Weeks 50-53; the secondary endpoint was dose change over time. The trial is registered at www.ClinicalTrials.gov, number NCT00394953. RESULTS: Baseline characteristics were similar between groups. One hundred and fifty-seven of 245 patients treated with methoxy polyethylene glycol-epoetin beta and 99 of 245 patients with darbepoetin alfa met the response definition (64.1% and 40.4%; P < 0.0001). Doses increased by 6.8% with methoxy polyethylene glycol-epoetin beta and 58.8% with darbepoetin alfa during once-monthly treatment. Death rates were equal between treatments (5.7%). Most common adverse events included hypertension, procedural hypotension, nasopharyngitis and muscle spasms, with no differences between groups. CONCLUSIONS: Methoxy polyethylene glycol-epoetin beta maintained target haemoglobin more successfully than darbepoetin alfa at once-monthly dosing intervals despite dose increases with darbepoetin alfa.

C.E.R.A. once every 4 weeks in patients with chronic kidney disease not on dialysis: The ARCTOS extension study.

C.E.R.A., a continuous erythropoietin receptor activator is approved for the treatment of anemia in patients with chronic kidney disease (CKD). The ARCTOS (administration of C.E.R.A. in CKD patients to treat anemia with a twice-monthly schedule) phase 3 study demonstrated the efficacy and safety of C.E.R.A. in correcting anemia when administered once every 2 weeks (Q2W) subcutaneously in patients with CKD not on dialysis. We assessed the feasibility and long-term safety of converting patients who responded to treatment with C.E.R.A. Q2W to C.E.R.A. once every 4 weeks (Q4W) during a 24-week extension period. After the core ARCTOS study period (28 weeks), 296 patients entered the 24-week extension period. At week 29, patients who responded to C.E.R.A. Q2W during the core period were rerandomized to receive subcutaneous C.E.R.A. Q2W or Q4W. Patients in the comparator arm could receive darbepoetin alfa once weekly or Q2W. Dosage was adjusted to maintain hemoglobin (Hb) between 11 and 13 g/dL. Mean Hb levels remained stable in all groups, and were comparable at the end of the extension period (mean [standard deviation], C.E.R.A. Q2W, 11.92 [0.90] g/dL; C.E.R.A. Q4W, 11.70 [0.86] g/dL; darbepoetin alfa, 11.89 [0.98] g/dL). Mean within-patient standard deviation values for Hb were also comparable in all groups (0.66, 0.62, and 0.65 g/dL for C.E.R.A. Q2W, C.E.R.A. Q4W and darbepoetin alfa, respectively). All treatments were well tolerated. Subcutaneous C.E.R.A. Q4W is safe and effective in maintaining stable Hb levels in patients with CKD not on dialysis following correction with subcutaneous C.E.R.A. Q2W.

Clinical, radiological, and biochemical features of a bilateral buttock amyloidoma emerging after 27 years of hemodialysis.

Deposition of amyloid in the buttock is a rare complication of dialysis related amyloidosis (DRA), but this localization is even rarer in other types of amyloidoses. We report here the clinical, radiological, and biochemical features of a patient who incurred into this complication after 27 years of hemodialysis. Imaging of the amyloid deposition by magnetic resonance imaging (MRI) documents the amyloid infiltration in the muscles of the buttock region and highlights a peculiar feature of amyloid fibrils deposition in the subcutaneous fat. The amyloid deposition is confirmed by biochemical and microscopic analysis of fibrils extracted from a biopsy specimen. Review of literature and the features of this case lead to speculation that the peculiar involvement of the buttock region including muscles and subcutaneous fat in DRA might derive from the propagation of amyloid initially deposited in the hip joint.

Predictive role of preoperative lymphoscintigraphy on the status of the sentinel lymph node in clinically node-negative patients with cutaneous melanoma.

We reviewed our experience to assess the predictive role of preoperative lymphoscintigraphy with regard to the pathological status of sentinel lymph node (sN) in patients with cutaneous melanoma, to optimize the surgical treatment planning with regard to the use of intraoperative frozen section examination of sN. Eighty-eight patients with clinically node-negative cutaneous melanoma pT1b-T4 stage underwent preoperative lymphoscintigraphy for the lymphatic mapping of sN. A lymphoscintigraphic 'score' (from L1 to L5) was developed based on the ratio of radiotracer concentration within sN nodes as compared with the injection site. Our score allowed us to foresee that sN of patients with thick melanomas (T3 and T4) and a low preoperative score (L1-L2-L3) had a 90% expected likelihood (P<0.001) of harboring metastasis, whereas sN in patients with thin melanomas (T1b-T2) and high preoperative score (from L4 to L5) showed a 100% likelihood of being metastasis free. In conclusion, the sN is a reliable predictor of regional lymph node status in patients with cutaneous malignant melanoma. Moreover, we suggest that a low score (L1-L2-L3) associated with a thick melanoma is a good predictive factor of the positive sN involvement. This information could be useful in scheduling the intraoperative frozen-section examination with an expected benefit of a positive test in almost 90% of patients. Such patients might be selected for a 'one-stage' procedure with a more effective cost/benefit ratio and decreased hospitalization costs.

Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients.

BACKGROUND: This pilot study evaluates the feasibility of axillary reverse mapping (ARM) during sentinel lymph node biopsy (SLNB) in breast cancer patients. METHODS: This study included 72 women with new breast cancer diagnosis, tumor size <2 cm, and clinically negative axilla. At the time of surgery, 2 mL of dermal blue patent were injected intradermally, subcutaneously, and intramuscularly in the ipsilateral upper inner arm in order to map and preserve the lymphatics of the arm. Blue arm lymphatics were preserved when in SLNB field. Microsurgical lymphatic-venous anastomosis (LYMPHA) was performed in women who underwent ALND. RESULTS: In 27 of 72 patients (37.5%), the blue lymphatics draining the arm were observed in the SLNB field. In all these patients, the blue lymphatics were preserved. During ALND, the blue lymphatics draining the arm were visible in 8 out of 9 patients (88.9%); in all these women, the LYMPHA procedure was performed. All ARM blue nodes removed during ALND were negative for malignancy. At 9-month follow-up, no patient had lymphedema. CONCLUSIONS: Arm lymphatic drainage can be observed in the SLNB field in 37.5% of the cases. Using the ARM during SLNB may facilitate the preservation of lymphatics draining the arm.