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Loss-of-function mutations in MECP2 are associated to Rett syndrome (RTT), a severe neurodevelopmental disease. Mainly working as a transcriptional regulator, MeCP2 absence leads to gene expression perturbations resulting in deficits of synaptic function and neuronal activity. In addition, RTT patients and mouse models suffer from a complex metabolic syndrome, suggesting that related cellular pathways might contribute to neuropathogenesis. Along this line, autophagy is critical in sustaining developing neuron homeostasis by breaking down dysfunctional proteins, lipids, and organelles.Here, we investigated the autophagic pathway in RTT and found reduced content of autophagic vacuoles in Mecp2 knock-out neurons. This correlates with defective lipidation of LC3B, probably caused by a deficiency of the autophagic membrane lipid phosphatidylethanolamine. The administration of the autophagy inducer trehalose recovers LC3B lipidation, autophagosomes content in knock-out neurons, and ameliorates their morphology, neuronal activity and synaptic ultrastructure. Moreover, we provide evidence for attenuation of motor and exploratory impairment in Mecp2 knock-out mice upon trehalose administration. Overall, our findings open new perspectives for neurodevelopmental disorders therapies based on the concept of autophagy modulation., Competing Interests: Disclosure and competing interests statement The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Supermicrosurgical lymphaticovenular anastomosis (LVA) is increasingly being recognized as a first-line treatment of limb lymphedema because it is minimally invasive and highly effective. Lymphoscintigraphy and indocyanine green (ICG) lymphography are the two most commonly performed diagnostic imaging examinations to establish the indication and plan the procedure for patients affected by limb lymphedema. In a small group of patients, the information between these two imaging tools can be discordant, showing different anatomical drainage pathways or the absence of drainage and dermal backflow in one examination and valid drainage pathways in the other. The purpose of this study is to examine the types of possible discrepancies between lymphoscintigraphy of the superficial system and ICG lymphography and to describe the surgical outcomes after LVA for patients presenting with such discrepancies., Methods: We retrospectively reviewed the data of all patients who underwent LVA for upper or lower limb lymphedema between July 2015 and July 2023. From this series, we identified a group of patients with nonconcordant imaging results from lymphoscintigraphy and ICG lymphography before lymphatic surgery. Nonconcordant findings were described in terms of "pattern discordance" and "pathway discordance." The surgical outcome was measured by the change in the mean circumference of the limb after surgery. The changes between the preoperative and postoperative limb measures were analyzed using the Student t test. P values < .05 were considered significant., Results: A total of 28 patients with limb lymphedema exhibited inconsistencies between preoperative lymphoscintigraphy of the superficial system and ICG lymphography. Among these patients, 14 experienced pattern discordance, 13 had pathway discordance, and 1 patient had both. After LVA, we observed a significant reduction in the average circumference of the affected limb in the analyzed group., Conclusions: The discrepancy in the information between lymphoscintigraphy and ICG lymphography in the preoperative study of patients affected by limb lymphedema is rare but possible. This phenomenon is still not fully explained; however, our results suggest that it does not correlate with the outcome of supermicrosurgical LVAs., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication., Methods: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death., Results: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001)., Conclusions: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality., Trial Registration: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Lymphoscintigraphy is the criterion-standard method for diagnosing lymphedema, and there is no universally standardized imaging modality. In our center, we use a new approach: rest/stress intradermal lymphoscintigraphy., Methods: We tested 231 consecutive patients with suspected lymphedema. All patients were studied after a complex physical therapy program to reduce edema. Two doses of 99m Tc-nanocolloid were injected intradermally. Two static planar scans were taken at rest following tracer injection. Next, patients performed an isotonic muscular exercise for 2 minutes followed by postexercise scans. Subsequently, a prolonged exercise was performed for 30 to 40 minutes, after which delayed scans were taken. Abnormal patterns were distinguished into minor or major findings, according to severity., Results: We identified superficial lymphatic vessels and regional lymph nodes in approximately 80% of limbs. Deep vessels were visualized in 26% of limbs. Minor findings were reported in 22.7% of limbs examined, whereas major findings were reported in 53.2% of limbs., Conclusion: We observed major findings including lymph stagnation, extravasation, or dermal backflow in a significantly higher percentage of limbs with secondary lymphedema than in primary. We also observed the deep lymphatic pathways in a significantly higher percentage of limbs with primary lymphedema. Intradermal radiotracer injection, combined with isotonic muscular exercise, may offer a better and faster imaging of lymphatic pathways, evaluating the effects of muscular exercise on lymphatic drainage. Based on the in-depth information of the lymphatic pathways provided by rest/stress intradermal lymphoscintigraphy, microsurgeons can obtain important functional information to perform supermicrosurgical lymphatic-venous anastomosis or vascularized lymph node transfer., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Effective lymphaticovenular anastomosis (LVA) requires identification of functioning lymphatics, which are not always visible with contrast-based imaging in advanced-stage lymphedema patients. Ultrasound (US) allows to identify preoperatively functioning lymphatic vessels even in limbs severely affected by lymphedema. Moreover, in our experience, we observed an interesting clinical sentry in advanced-stage lymphedema patients, the hand/foot sign that is analyzed in this paper., Patients and Methods: From January 2016 to January 2019, 76 consecutive advanced-stage secondary lymphedema patients underwent LVA. Preoperative planning included lymphoscintigraphy, indocyanine-green lymphography (ICG-L) and US. Patients' features, the hand/foot sign (preservation of more normal skin on the dorsum of the hand or foot), lymphatic degeneration, quantitative, qualitative, and composite outcomes at 1-year follow-up were evaluated., Results: An average number of 3±0.1 LVA was performed in upper limb lymphedema (ULL) (range 2-5, 47 patients) and of 4±1.08 LVAs in lower limb lymphedema (LLL) cases (range 4-7, 29 patients). The composite outcome was positive in 45 cases (59.7%). The "negative" hand /foot sign was significantly associated with presence of functioning lymphatic channels. The incidence of adverse outcomes was significantly higher in patients with positive hand/foot sign., Conclusion: Patients with no functioning lymphatic vessels detectable by lymphoscintigraphy and ICG-L may still have functioning lymphatic channels that can be identified preoperatively by ultra-high-frequency ultrasound and salvaged by LVA. The "hand/foot sign" is a simple clinical sentry that appears to be correlated with higher probability of being able to localize functional lymphatics for potential lymphovenous bypass surgery., Competing Interests: Declaration of Competing Interest Dr Akitatsu Hayashi and Dr Giuseppe Visconti are co-Editor of the book “Supermicrosurgical Lymphaticovenular Anastomosis: a Practical Textbook”. The other authors have no any interest to disclose., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: Radical cystectomy with permanent urinary diversion is the gold standard treatment for invasive muscle bladder cancer. Hydronephrosis is common in these patients, but Ultrasound (US) or Computed Tomography Urography (CTU) scan are unable to discriminate obstructive from non-obstructive hydronephrosis. We used Diuresis Renography (DR) with F + 10 in seated position (sp) method in the identification of patients with a Uretero-ileal Anastomosis Stricture (UAS) who would benefit from surgical therapy., Methods: We studied 39 asymptomatic patients, who underwent radical cystectomy and urinary diversion. Based on radiological findings (US, CTU) 44 kidneys were hydronephrotic. All patients underwent a 99m Tc-MAG3 DR with F + 10(sp) method. We acquired a DR for 20 min with the patient in a seated position. Patient drank 400-500 mL of water at 5 min after tracer injection and received a 20 mg bolus of Furosemide at 10 min during dynamic acquisition. The indices Time to peak, diuretic half time, and 20 min/peak ratio have been evaluated. Retrograde pyelography confirmed UAS in all patients with DR obstructive findings. We repeated DR as follow-up in two subgroups of patients., Results: DR with F + 10(sp) method showed obstructive findings in 36 out of 44 hydronephrotic kidneys. 6 patients showed non-obstructive findings. 32 patients showed obstructive findings (20 out of 32 developed UAS within 12 months after surgery). Fifteen pts underwent a surgical treatment of UAS. In 1 patient with equivocal findings, we observed an ileo-ureteral reflux., Conclusions: The DR with F + 10(sp) method in the seated position has a lower uncertain diagnostic rate, compared to the radiological findings of US or CTU, in management of bladder cancer patients with urinary diversion. The semiquantitative indices diuretic half time and 20 min/peak ratio evaluated in a condition of favorable gravity reduce uncertain responses improving interobserver concordance., (© 2021. The Japanese Society of Nuclear Medicine.)

Introduction: In 1978, O'Reilly introduced the diuretic renogram using the F + 20 method. Initially, the patient was examined in the seated position. A dose of 40 mg furosemide was injected intravenously 20 min following tracer injection and dynamic acquisition was prolonged for 15-20 min. In 1992, the guidelines suggested to study patients in the supine position to avoid risk of diuretic-induced hypotension and reduce patient movement. Unfortunately, equivocal findings were reported in 15-30% of cases. Side effects such as bladder fullness and disruption because of voiding were reported. Several methods had been proposed in the supine position, such as the well-tempered diuretic renogram F + 20, F - 15, F0 and F + 2, with different time in minute of diuretic administration in relation to tracer injection. However, as confirmed by many studies, there was no clear evidence suggesting superiority among these methods. We suggest using the diuretic renogram with the F ± 10(sp) method for the diagnosis of obstruction in adult patients with hydronephrosis and for the follow-up in patients who underwent a surgical treatment of the urinary tract., Methods: We searched all international guidelines and articles of most influential authors published from 1978 to October 2020 on diuretic renogram., Results: We selected 60 articles., Discussion: F + 10(sp) method improves patient compliance avoiding bladder fullness-related problems, without need of catheterization. It allows for a more reliable quantification of the renal output, thanks to outflow indices that are favored by gravity effects., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Data from literature show a mean incidence of occult metastases of 33% in early OCSCC. The gold standard for most authors is a selective neck dissection and a routine pathological examination. 60-70% of unnecessary neck dissections with associated morbidity, can be avoided by using SNB. The aim of this study is to present the results of one of the major Italian centres for the SNB procedure, reserving neck dissection only for proven positive lymphatic metastases., Methods: From July 2004 to March 2015, 48 patients with transorally resectable cT1-T2N0 oral SCC were submitted to a lymphoscintigraphic examination one-three hours before surgery and a radio-guided SNB (same day protocol). Patients with a negative SNB were checked every 3 months by ultrasound examination. The minimum follow-up was 5 years., Results: Sentinel nodes were found in all cases, with 71% localized in the ipsilateral neck only in levels I-II. Metastases were found in 15 out of 48 cases (31.2%), on levels I, II and III. Further metastatic nodes were found in 6 cases in the neck dissection specimen. In the cohort of 33 patients with SNB negative at 5 years, no-one had a recurrence on the ipsilateral neck., Conclusion: This study confirms the accuracy of SNB in predicting the presence of occult metastases, sparing the need for unnecessary neck dissection in 70% of cases. The same day protocol is designed to detect sentinel nodes, which are almost always on neck level I-II, thereby limiting the number of nodes examined and the extension of the surgical approach.

Lipedema is a chronic and progressive disease characterized by a symmetrical and bilateral swelling of the lower extremities. In general, the feet are not involved. Lipedema is believed to affect nearly 1 in 9 adult women worldwide. Despite this relatively common disease, lipedema is often confused with primary lymphedema or obesity. In clinically advanced lipedema stages, fat continues to build up and may block the lymphatic vessels causing a secondary lymphedema (Lipo-Lymphedema). We consecutively evaluated 54 women with a clinical diagnosis of lower limbs lipedema. Two doses of 99mTc-nanocolloid were injected intradermally at the first intermetatarsal space and in the lateral malleolar area. Two static planar scans were taken at rest immediately following the intradermal injection. Subsequently, all patients were asked to perform an isotonic muscular exercise (stepping) for 2 min. Then, post exercise scans were performed to monitor the tracer pathway. Subsequently, the patient was asked to take a 30-40 min walk (prolonged exercise) and delayed scans were acquired. In early clinical stages, the lymphatic flow is usually preserved and the rest/stress intradermal lymphoscintigraphy may visualize a normal lymphatic drainage with a frequent pattern (tortuous course) of the leg lymphatic pathway. In clinically advanced stages, lymph stagnation areas were observed. Unlike obesity, lipedema fat storage is resistant to dietary regimen, bariatric surgery, and physical activity. Surgical treatment (tumescent liposuction and reductive surgery) is the most effective treatment to remove adipose tissue. Complex decongestive therapies are helpful in reducing the lymph stagnation, especially in patients with advanced lipolymphedema., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 World Journal of Nuclear Medicine.)

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 99m Tc-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., (Copyright © 2019 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Stress-lymphoscintigraphy evaluates the effects of exercise on lymph drainage. Results may predict outcomes of complex physical therapy as a first-line lymphedema treatment. Microsurgical approaches are best in patients with lymphangectasia or dermal backflow. Lymphatic pathway mapping helps plan lympho-venous anastomoses. For improved lymphatic visualization, we suggest a scan at rest, after a quick exercise (stepping or weight lifting for 2 min) and delayed scanning after prolonged symptom limited exercise (walking or hand squeezing for 30-40 min). In advanced lymphedema, identification of lymph pathways and residual regional lymph nodes might be difficult. In these patients, lymph node transplant is suggested.

Obstructive nephropathy may be suspected for the incidental detection of dilated renal collecting system at ultrasonography, CT or MRI. A dilated renal collecting dilation (calyco-pelvis or ureteres) might be related 1) to an anatomical variant of the excretory tract without obstruction and, therefore, without consequence on renal function, or 2) to an obstruction/stenosis of the urinary tract that may cause a damage of kidney function. In the present review we annotated the various methods proposed for Diuresis Renography (DR) used with the purpose to make early diagnosis of obstructive nephropathy. First, the F + 20 method (i.e. furosemide 40 mg injected IV 20 min after radiotracer injection) in seated position (sp) (F + 20 (sp) ) was reported to distinguish between an anatomical dilation from an anatomical obstruction of the urinary tract. It was also suggested to perform DR with the patient in supine or prone position in order to minimize possible furosemide-induced hypotension and patient's movements during exam. Other DR methods were proposed administering furosemide EV to the patient in supine position at different times: F-15 (furosemide injected IV 15 min prior to radiotracer), F0 (furosemide injected contemporary to radiotracer), F + 20 (furosemide injected 20 min after the radiotracer), F-20 and Well Tempered (other than F + 20 this modality requires saline infusion for all duration of the test plus bladder catheterization). Unfortunately, in all the above described DR methods with patientin supine position, despite the furosemide administration, a sensitive slowing down of urinary outflow could be related to the supine position itself of the patient during the examination. Lastly, there are reports of a new DR method based on furosemide IV injection 10 min after radiotracer with the patient in seated position, F+10 (sp) . This method allows a better timing between hydration (400 mL of water) at 5 min, and the injection of relatively low dose of furosemide (20 mg), thus avoiding side effects as diuretic-induced hypotension and favouring bladder filling, therefore ameliorating patient compliance and reducing equivocal responses., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Sentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma., Methods: These practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI). These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the "2018 Sentinel Node Biopsy in Head and Neck Consensus Conference"., Conclusion: The present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients.

Background: We report our clinical experience of a supraclavicular lymph node flap (LNF) using a novel method of harvesting based on the compartimental lymphatic and vascular anatomy of the right posterior neck triangle, which allows to harvest two independent LNFs from the same donor site., Patients and Methods: We report a case series of 10 consecutive patients affected by cancer-related lower extremity lymphedema, who underwent compartimental dual LNF transfer from the right supraclavicular area to the affected lower limb, from August 2015 to March 2017. The superficial compartment flap (venous flap along the external jugular vein) was anastomosed in a flow-through fashion along the course of the great saphenous vein in the knee region, whereas the deep compartment flap (transverse cervical artery/vein flap) was anastomosed in an end-to-end fashion to the medial sural artery and comitantes vein. Flap viability was checked by color Doppler ultrasound postoperatively. Patients were assessed preoperatively and underwent follow-up at 6 and 12 months after surgery. Data were prospectively collected., Results: All the flaps resulted to be viable. No major postoperative complications were observed neither at the donor nor at the recipient sites. Patients did not report dysesthesia of the homoteral chest. An overall reduction in the lower extremity lymphedema (LEL) index (mean ± SD: 33.7 ± 22.5) and an improvement in the lymph flow and tracer appearance time at postoperative lymphoscintigraphy were observed. All the patients reported an improved quality of life after surgery., Conclusions: Compartimental supraclavicular dual LNF harvest seems promising in the treatment of peripheral lymphedema. Sparing of supraclavicular nerves might reduce the morbidity associated with the conventional surgical approach. Larger studies are needed to confirm our findings., Level of Evidence: IV, therapeutic study., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

It is widely recognized that airway inflammation and remodeling play a key role not only in the central airway but also small airway pathology during asthma. Nociceptin/Orphanin FQ (N/OFQ), an endogenous peptide, and its receptor N/OFQ peptide (NOP) are involved in airway hyperresponsiveness (AHR). We studied a murine model of AHR in order to understand the role of N/OFQ in the inflammation and remodeling of the small airways. Balb/c mice were sensitized to ovalbumin (OVA). At days 0 and 7 (pre-OVA sensitization) or from day 21 to 23 (post-OVA sensitization), the mice were treated intraperitoneally with N/OFQ or saline solution. After the last OVA challenge, all OVA-sensitized mice were aerosol-challenged with 1% OVA in PBS for 48 h, and then euthanized. Small airway compliance (sC aw ) was measured and lung samples were collected for histological and molecular evaluations such as perimeter and diameter of small airway, total wall area, airway smooth muscle (ASM) thickness and number of alveolar attachments. Both pre- and post-OVA sensitization N/OFQ treatments induced: (1) increases in sC aw ; (2) reduction of the bronchial wall thickness; (3) attenuation of the hyperplastic phase of airway smooth muscle mass; and (4) protection against loss of alveolar attachments compared with saline solution treatments. These results suggest that N/OFQ protects against inflammation, and mechanical damage and remodeling of small airways caused by OVA sensitization, suggesting a new potential therapeutic target for asthma., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Pulmonary emphysema is a respiratory condition characterized by alveolar destruction that leads to airflow limitation and reduced lung function. Although with extensive research, the pathophysiology of emphysema is poorly understood and effective treatments are still missing. Evidence suggests that mesenchymal stem cells (MSCs) possess the ability to engraft the injured tissues and induce repair via a paracrine effect. Thus, the aim of this study was to test the effects of the intratracheal administration of lung-derived mouse MSCs in a model of elastase-induced emphysema. Pulmonary function (static lung compliance) showed an increased stiffness induced by elastase, while morphometric findings (mean linear intercept and tissue/alveolar area) confirmed the severity of alveolar disruption. Contrarily, MSC administration partially restored lung elasticity and alveolar architecture. In the absence of evidence that MSCs acquired epithelial phenotype, we detected an increased proliferative activity of aquaporin 5- and surfactant protein C-positive lung cells, suggesting MSC-driven paracrine mechanisms. The data indicate the mediation of hepatocyte growth factor in amplifying MSC-driven tissue response after injury. Our study shed light on supportive properties of lung-derived MSCs, although the full identification of mechanisms orchestrated by MSCs and responsible for epithelial repair after injury is a critical aspect yet to be achieved.

Cancer treatments with axillary or pelvic lymph nodes dissection and radiation place patients at lifelong risk for the development of secondary lymphedema. Our aim was to evaluate the role of stress lymphoscintigraphy for early detection and management of secondary lymphedema., Methods: Stress lymphoscintigraphy was performed within 1 year after surgery and the completion of chemotherapy and radiation treatments. All patients were classified by the International Society of Lymphology clinical stages from 0 to 3. A dose of 50 MBq of 99mTc-HSA-nanocolloidal in 0.4mL was injected intradermally at the first and fourth intermetacarpal spaces on the hand, for the upper limb with edema, or at the first intermetatarsal space and at the lateral malleolus for lower extremities. Two planar static scans at rest were acquired immediately after tracer injection. Stress scans were acquired after weight lifting for upper extremity or stepping for 2 minutes for lower-extremity edema. After that, the patients underwent prolonged muscular exercise limited by symptoms, and later scans were acquired at 60 minutes to visualize regional lymph nodes and the effects of sustained muscular exercise. Transport Index was evaluated., Results: Five patterns of lymphoscintigraphy were observed. In our experience, patients with types I to III pattern benefit from an exercise program as a first-line treatment. Patterns IVand V seem to be predictive of lymphedema., Conclusions: The abnormal patterns found may provide the basis for earlier complex physical therapy or microsurgical treatment of lymphatic disorders in patients resulting in improved outcomes.

Introduction: Supermicrosurgical lymphatic-venous anastomosis (LVA) can improve limbs lymphedema. We describe a technique that we employ for preoperative lymphatic mapping of the upper limb (UL), when indocyanine green (ICG) lymphography shows only dermal backflow (DB) and no lymphatic vessel is detectable., Patients and Methods: Sixteen patients undergoing LVA for unilateral UL lymphedema, showing "stardust" or "diffuse" DB pattern, were included. Demographic, clinical data, and limbs measurements were recorded. LymQoL arm questionnaire was administered. Mean age of patients was 58.8 ± 13.1 years. Fifteen were females and 1 male. Lymphatic anatomy of the healthy limb was investigated by ICG lymphography and reported on the affected limb by a four steps technique: marking the main lymphatic pathway on the healthy limb, measuring of the distances at seven levels between the pathway and a line joining fixed landmarks, reporting these measurements on the affected limb with a correction proportional to the degree of swelling, marking skin incisions at the intersection of this pathway with venules, individuated by near infrared light system. Results were analyzed by postoperative questionnaire and changes of limb measurements., Results: For every limb, we could find 3 ± 0.73 incision sites each containing at least one lymphatic vessel suitable for anastomosis. In every patient, we could perform 3.38 ± 0.62 anastomoses. Mean follow-up was 12.13 ± 2.73 months. After surgery, mean preoperative QoL score increased from 5.5 to 7.9 (P < .001), and mean difference between the mean circumferences of the affected and healthy limbs decreased from 4.3 ± 1.3 to 2.5 ± 1.3 cm, showing improvement of swelling after surgery (P < .01)., Conclusion: This technique allowed to preoperatively map UL lymphatics even if diffuse DB was present., (© 2017 Wiley Periodicals, Inc.)

In this short review, the technical and clinical improvements of the sentinel lymph node biopsy in head and neck cancer are presented.

Background: The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs) can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce., Objectives: To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model., Methods: GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro., Results: Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties., Conclusion: Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue remodeling.

Purpose: Nuclear imaging plays a crucial role in lymphatic mapping of oral cancer. This evaluation represents a subanalysis of the original multicenter SENT trial data set, involving 434 patients with T1-T2, N0, and M0 oral squamous cell carcinoma. The impact of acquisition techniques, tracer injection timing relative to surgery, and causes of false-negative rate were assessed., Methods: Three to 24 hours before surgery, all patients received a dose of Tc-nanocolloid (10-175 MBq), followed by lymphoscintigraphy. According to institutional protocols, all patients underwent preoperative dynamic/static scan and/or SPECT/CT., Results: Lymphoscintigraphy identified 723 lymphatic basins. 1398 sentinel lymph nodes (SNs) were biopsied (3.2 SN per patient; range, 1-10). Dynamic scan allowed the differentiation of sentinel nodes from second tier lymph nodes. SPECT/CT allowed more accurate anatomical localization and estimated SN depth more efficiently. After pathological examination, 9.9% of the SN excised (138 of 1398 SNs) showed metastases. The first neck level (NL) containing SN+ was NL I in 28.6%, NL IIa in 44.8%, NL IIb in 2.8%, NL III in 17.1%, and NL IV in 6.7% of positive patients. Approximately 96% of positive SNs were localized in the first and second lymphatic basin visualized using lymphoscintigraphy. After neck dissection, the SN+ was the only lymph node containing metastasis in approximately 80% of patients., Conclusions: Best results were observed using a dynamic scan in combination with SPECT/CT. A shorter interval between tracer injection, imaging, and surgery resulted in a lower false-negative rate. At least 2 NLs have to be harvested, as this may increase the detection of lymphatic metastases.

Epidemiological data suggest that obesity represent an important risk factor for asthma, but the link between excess fat and airway hyperresponsiveness (AHR) and inflammation is not fully understood. Recently, a key role in physiopathologic conditions of lungs has been given to adiponectin (Acrp30). Acrp30 is one of the most expressed adipokines produced and secreted by adipose tissue, showing an intriguing relationship with metabolism of sphingolipids. Sphingosine-1-phosphate (S1P) has been proposed as an important inflammatory mediator implicated in the pathogenesis of airway inflammation and asthma. In the present study we analyze the effects of recombinant Acrp30 administration in an experimental model of S1P-induced AHR and inflammation. The results show that S1P is able to reduce endogenous Acrp30 serum levels and that recombinant Acrp30 treatment significantly reduce S1P-induced AHR and inflammation. Moreover, we observed a reduction of Adiponectin receptors (AdipoR1, AdipoR2 and T-cadherin) expression in S1P treated mice. Treatment with recombinant Acrp30 was able to restore Acrp30 serum levels and adiponectin receptors expression. These results could indicate the ability of S1P to modulate the Acrp30 action, by modulating not only the serum levels of the protein, but also its receptors. Taken together, these data suggest that adiponectin could represent a possible biomarker in obesity-associated asthma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Structural changes contribute to airway hyperresponsiveness and airflow obstruction in asthma. Emerging evidence points to the involvement of c-kit + cells in lung homeostasis, although their potential role in asthma is unknown. Our aim was to isolate c-kit + cells from normal mouse lungs and to test whether these cells can interfere with hallmarks of asthma in an animal model. Adult mouse GFP-tagged c-kit + cells, intratracheally delivered in the ovalbumin-induced airway hyperresponsiveness, positively affected airway remodeling and improved airway function. In bronchoalveolar lavage fluid of cell-treated animals, a reduction in the number of inflammatory cells and in IL-4, IL-5, and IL-13 release, along with an increase of IL-10, was observed. In MSC-treated mice, the macrophage polarization to M2-like subset may explain, at least in part, the increment in the level of anti-inflammatory cytokine IL-10. After in vitro stimulation of c-kit + cells with proinflammatory cytokines, the indoleamine 2,3-dioxygenase and TGF β were upregulated. These data, together with the increased apoptosis of inflammatory cells in vivo, indicate that c-kit + cells downregulate immune response in asthma by influencing local environment, possibly by cell-to-cell contact combined to paracrine action. In conclusion, intratracheally administered c-kit + cells reduce inflammation, positively modulate airway remodeling, and improve function. These data document previously unrecognized properties of c-kit + cells, able to impede pathophysiological features of experimental airway hyperresponsiveness., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Purpose: Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma., Methods: An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB was undertaken with an average of 3.2 nodes removed per patient. Patients were excluded if the sentinel node (SN) could not be identified. A positive SN led to a neck dissection within 3 weeks. Analysis was performed at 3-year follow-up., Results: An SN was found in 99.5% of cases. Positive SNs were found in 23% (94 in 415). A false-negative result occurred in 14% (15 in 109) of patients, of whom eight were subsequently rescued by salvage therapy. Recurrence after a positive SNB and subsequent neck dissection occurred in 22 patients, of which 16 (73%) were in the neck and just six patients were rescued. Only minor complications (3%) were reported following SNB. Disease-specific survival was 94%. The sensitivity of SNB was 86% and the negative predictive value 95%., Conclusion: These data show that SNB is a reliable and safe oncological technique for staging the clinically N0 neck in patients with T1 and T2 oral cancer. EORTC Protocol 24021: Sentinel Node Biopsy in the Management of Oral and Oropharyngeal Squamous Cell Carcinoma., (Copyright © 2015. Published by Elsevier Ltd.)

Objective: The objective of this study was to compare 2 diuretic renography procedures: F-15 versus F+10(sp) for diagnosis of obstructive uropathy in adults., Methods: Thirty-six patients with unilateral or bilateral hydronephrosis had 2 consecutive Tc-MAG3 diuretic renograms within 7 days, using the widely used procedure F-15 in supine position, and a new seated-position procedure whereby the patient drinks 400 to 500 mL of water at 5 minutes and receives an injection of 20 mg of furosemide at 10 minutes [F+10 (sp)]., Results: F-15 showed nonobstructive results in 63.9% of kidneys, obstruction in 26.4%, and equivocal findings in 6.9% and was not applicable in 2.8%. F+10(sp) showed nonobstructive results in 70.9%, obstruction in 27.8%, and equivocal result in 1.4% of kidneys. Nephroptosis was observed by F+10(sp) in 22.2% of kidneys. Adverse effects reported for the F-15 were hypotension in 2 patients, renal colic in 3 patients, and interruption due to voiding in 5 patients. No adverse effects were reported for F+10(sp)., Conclusions: This study shows that the F+10(sp) procedure reduces the equivocal findings of F-15 procedure in 36 patients. It can improve the accuracy and compliance, avoiding adverse effects and reducing bladder filling-related problems.

Background: Dilation of the renal pelvis is a problem Urologists have often to deal with. One of the key aspects is to clear if the dilation is the consequence of an obstruction to the outflow or a simple anatomic variant. Aim of this study was to compare two diuretic renographic procedures, F-15 vs the new procedure F+10SP (Seated Position) in a group of hydronephrotic patients, in order to increase the accuracy in the differential diagnosis between non-obstructive and obstructive dilation., Materials and Methods: 34 Patients (14 male, 20 female, 18-71 yrs range), 27 pts having an unilateral hydronephrosis and 7 pts a bilateral hydronephrosis diagnosed by ultrasound, were enclosed in the study. They were subjected to two 99mTc-MAG3 diuretic renography with furosemide consecutively, with different modalities: 1) 40 mg of furosemide were administered IV to patient in supine position 15 minutes before tracer injection (Test F-15, by English); 2) the new procedure: 20 mg of furosemide were administered IV to patient in Seated Position (SP), 10 minutes after tracer injection during dynamic acquisition (Test F+10 SP). The average interval between the two tests was 7 days. Two different physicians analyzed all the tests. The results were classified as: non-obstruction (only F+10SP can distinguish between normal and dilated without obstruction), obstruction, equivocal and not applicable., Results: Among the 68 renal units (RU) included in the analysis, the F+10SP test showed normal findings in 21 RU (30,8%), dilation without obstruction in 21 RU (30,8%), obstruction in 25 RU (36.8%) and equivocal result in 1 RU. The F-15 renography showed non-obstructive results in 35 RU (51.5%), obstruction in 20 RU (29.4%) and equivocal findings in 11 RU (16.1%); the test was not applicable in 2 RU (2.9%) due to insufficient renal function. Side effects reported for the F-15 renogram were hypotension in 1 patient, renal colic in 3 patients, bladder filling in 13 patients, disruption because of voiding in 4 patients. No complications were observed during or after the F+10SP renography. The 20 RU diagnosed with obstruction at the F-15 test were considered obstructed also at the F+10SP test., Conclusions: The "equivocal" test rate lowered from 16% for the F-15 test to less than 1.5% for the new F+10 SP test. The F+10SP procedure is easy, well tolerated, time saving and seems to be a more reliable tool in assessment of obstructive uropathy in adults.

In this technical report, prepared following the kind invitation of Professor D'Amore, we describe the evolution in the methodology of performing the limb lymphoscintigraphy. In details we described and compared the rest protocol with subcutaneous injection of the radio-colloids vs. the exercise intradermal injection protocol. The latter appears to be faster and easier to interpret, moreover allowing an adequate measurements of quantitative parameters of lymph drainage and distribution., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to evaluate the effect of implementing a new technique, intradermal injection lymphoscintigraphy, at rest and after muscular exercise on the functional assessment of the lymphatic system in a group of patients with delayed or absent lymph drainage., Methods: We selected 44 patients (32 women and 12 men; 15 of 44 with upper limb and 29 of 44 with lower limb lymphoedema). Thirty of 44 patients had bilateral limb lymphoedema and 14 of 44 had unilateral disease; 14 contralateral normal limbs were used as controls. Twenty-three patients had secondary lymphoedema after lymphadenectomy and the remaining 21 had idiopathic lymphoedema. Each of the 44 patients was injected with 50 MBq (0.3-0.4 ml) of (99m)Tc-albumin-nanocolloid, which was administered intradermally at the first interdigital space of the affected limb. Two planar static scans were performed using a low-energy general-purpose collimator (acquisition matrix 128 x 128, anterior and posterior views for 5 min), and in which drainage was slow or absent, patients were asked to walk or exercise for 2 min. A postexercise scan was then performed to monitor and record the tracer pathway and the tracer appearance time (TAT) in the inguinal or axillary lymph nodes., Results: The postexercise scans showed that (i) 21 limbs (15 lower and six upper limbs) had accelerated tracer drainage and tracer uptake in the inguinal and/or axillary lymph nodes. Two-thirds of these showed lymph stagnation points; (ii) 27 limbs had collateral lymph drainage pathways; (iii) in 11 limbs, there was lymph drainage into the deeper lymphatic channels, with unusual uptake in the popliteal or antecubital lymph nodes; (iv) six limbs had dermal backflow; (v) three limbs did not show lymph drainage (TAT=not applicable). TAT=15 + or - 3 min, ranging from 12 to 32 min in limbs with lymphoedema versus 5 + or - 2 min, ranging from 1 to 12 min in the contralateral normal limbs (P<0.001)., Conclusion: Intradermal injection lymphoscintigraphy gives a better imaging of the lymph drainage pathways in a shorter time, including cases with advanced lymphoedema. In some patients with lymphoedema, a 2-min exercise can accelerate tracer drainage, showing several compensatory mechanisms of lymph drainage. The effect of the exercise technique on TAT and lymphoscintigraphy findings could result in a more accurate functional assessment of lymphoedema patients.

Aim: To evaluate the role of dynamic lymphoscintigraphy with a same-day protocol for sentinel node biopsy in oral cavity cancer., Methods: Twenty-two consecutive patients affected by cT1-2N0 squamous cell carcinoma of the oral cavity were enrolled between September 2001 and November 2005. After a local anaesthetic (10% lidocaine spray), a dose of 30-50 MBq of Tc human serum albumin nanocolloid, in ml saline, was injected superficially (1-2 mm subendothelial injection) into four points around the lesion. Dynamic lymphoscintigraphy was acquired immediately (256x256 matrix, 5 min pre-set time, LEGP collimator) in lateral and anterior projections. The imaging was prolonged until the lymph nodes of at least two neck levels were visualized (time required min). About 3 h later (same-day protocol) the patients had a radioguided sentinel node biopsy. Elective neck dissection was performed in the first 13 patients; whereas the last nine patients had elective neck dissection only if the sentinel node was positive. Sentinel nodes were dissected into 1 mm thick block sections and studied by haematoxylin & eosin staining and immunohistochemistry (anticytokeratin antibody)., Results: The sentinel nodes were found on the 1st neck level in 13 cases, on the 2nd neck level in eight cases, and on the 3rd neck level in one case (100% sensitivity). The average number of sentinel nodes was 2.2 for each patient. The sentinel node was positive in eight patients (36%); with six of them having the sentinel node as the exclusive site of metastasis. No skip metastases were found in the 14 patients with negative sentinel node (100% specificity)., Conclusion: Our preliminary data indicate that superficial injections of radiocolloid and dynamic lymphoscintigraphy provide a high success rate in sentinel node identification in oral cavity cancers. Dynamic lymphoscintigraphy helps in distinguishing sentinel node from second-tier lymph nodes. The same-day protocol is advisable in order to correctly identify the first sentinel node, avoiding multiple and unnecessary node biopsies, without reducing sensitivity.

The routine use of a sentinel node biopsy (SNB) protocol in oral cavity squamous cell carcinomas (SCC) has been challenged on the basis of the elevated number of sentinel nodes (SNs) detected (>2.5) and on the multiply neck level involvement reported in several studies. These data limit the practical application of the protocol, because in such cases, it seems easier and safer to perform a selective neck dissection. The aim of our study is to perform radioguided surgery 1-3 h after lymphoscintigraphy (same day protocol) to detect the lymph nodes closest to the tumour site. In our study, 12 patients affected by cT1-2 N0 SCC of the oral cavity were submitted to a same day protocol of a lymphoscintigraphic examination (1-3 h before surgery) and a radioguided SNB. We used a hand-held gamma probe and performed an elective neck dissection on all patients. The SNs were found in all cases with 83% localised in the ipsilateral neck in only levels I-II. The mean number of SN detected was 2.1, with a mean pathological size of 13.8 mm measured on pathological specimen. Metastases were found in 5/12 cases (41.6%), on levels I, II and III and all were identified by step serial sectioning and routine H&E staining. This study confirms the accuracy of SNB in predicting the presence of occult metastases. This protocol is designed to detect SNs, which are almost always on neck level I and II, thereby limiting the number of nodes examined and the extension of the surgical approach.

A hierarchically structured composite material with interconnecting meso- and micropores has been developed with the aim to optimize zeolite performance. A general synthetic method has been developed that, in a controlled manner, allows for various types of nanosized zeolite to be incorporated into a three-dimensional mesoporous matrix. Nanosized zeolite Beta was used to exemplify this new approach, resulting in a system in which zeolite Beta shows a higher cracking activity per gram of zeolite than pure nanosized zeolite Beta for the model feed n-hexane. Additionally, FTIR studies of CO and NH3 adsorption revealed that the nature of the acid sites in the nanozeolite has been partially modified due to the interactions with the mesoporous matrix, TUD-1.

Purpose: Is to evaluate the role of the sentinel node (SN) radiolocalisation and its prognostic value in state T2N0M0 squamous cell carcinomas (SCC) of the lip., Materials and Methods: Between November 1999 and June 2002 we enrolled 11 consecutive patients (8m,3f) affected with lower lip SCC (7 pts.), labio-commissure (3 pts.) and upper lip (1 pt). Lymphoscintigraphy was performed three hours before surgery. After topical anaesthesia (Lidocaine spray 10%), 30-50MBq of Nanocoll-Tc99m diluted in a 0.3 ml physiological solution was injected intradermally, divided into two peri-lesional points. Planar static acquisition began immediately after the injection in order to visual lymph drainage pathways (lateral and/or anterior view, 512x512 matrix, 5 min. pre set time, LEGP collimator). All patients underwent only selective lymph adenectomy of the SN., Results: SN were visible in all patients within 5 minutes after the injection. In all patients the SNs were observed in the submandibular area (I neck level) in three patients a second SN was localized in latero cervical area (II neck level). All patients were staged SN negative. The average disease free interval for patients who underwent a selective lymph adenectomy of the SN was 20 months with continuing follow-up., Conclusions: We must stress the importance of performing an immediate exploratory dynamic or static scintigraphy within the first minutes of the radio tracer injection, in order to acquire a precise SN localisation and an accurate mapping of the tumour lymphatic pathways. SN radio localisation is especially beneficial in T2N0 stage patients where immediate lymphadenectomy is not necessary. It also saves time and cuts costs, which are specific goals in the current climate of health service management. Although our results are encouraging, a larger data base from multi centre trials with a five year follow-up would confirm the validity of our approach.

Background: The purpose of this paper is to present personal experience with sentinel node biopsy for the treatment of malignant melanoma. Technical details influencing the efficacy of the procedure are presented and the clinical, therapeutic and prognostic advantages of this technique discussed., Methods: A total of 390 consecutive patients with primary skin melanoma (T2-3,N0,M0) underwent sentinel node biopsy between March 1996 and May 2001. All patients underwent previous excisional biopsy of the primary lesion and clinical and radiographic examination to exclude lymphatic or systemic macroscopic spreading of the disease. Preoperative lymphoscintigraphy (99mTc nanocoll) was routinely performed in the last 315 patients. Intraoperative detection of the sentinel nodes was performed by perilesional, intradermical, injection of blue dye associated with a g probe (Neoprobe(R) 2000) in the last 315 patients. Sentinel nodes, serially sectioned, were all Haematoxylin-Eosin and immunohistochemically stained. All patients positive for micro-metastasis underwent radical lymphadenectomy. Comparative analysis between the incidence of metastasis in sentinel and non-sentinel nodes, according to the clinical stage of the disease, was done., Results: The overall detection rate of sentinel nodes was 97.4%. Relevant differences were found according to the site of dissection and the use of a g probe. The g-probe makes the procedure more effective, less invasive and less expensive. Timing and accuracy of the preoperative lymphoscintigraphy is a basic step of the procedure. The overall incidence of positive sentinel nodes was 14.7% with differences correlated with thickness of primary lesion (0.75-1.5 mm: 5,8%; 1.5-3 mm:18%; 3-4 mm: 24.6%). Metastasis in other non-sentinel nodes was found only with primary tumour thickness exceeding 2 mm., Conclusions: Sentinel node biopsy is a procedure requiring a multidisciplinary approach (surgery, nuclear medicine and pathology). A specific learning phase (>30 patients) is recommended to obtain reliable results.

Purpose: To optimize the lymphoscintigraphic procedure in the staging of malignant cutaneous melanoma., Material and Methods: Fifty-five patients (21 men and 34 women) were enrolled. Breslow thickness of the lesions ranged 0.75-1 mm (Clark III-IV) to 1-4 mm. Lymphoscintigraphy was performed with a large-view gamma camera equipped with a low-energy general purpose collimator, two weeks after melanoma excision. A single perilesional dose of 30-50 MBq nanocoll-Tc99m (volume 0.2-0.3 mL) was injected 18 hours before surgery (6 hours in head localizations). After injection a gentle local massage was applied. A planar static scintigraphy (matrix 512 x 512, pre-set time 5 min) in anterior and/or oblique view(s) was obtained 5-10 min after radiotracer injection. The skin projection of the first node was stained with an external radioactive marker. Fifteen minutes before surgery a blue-vital dye was injected around the lesion. A radioguided biopsy of the sentinel node was performed., Results: The site of the sentinel node was typical in 80% of patients. Two or three nodes were identified in 20% of patients. An unexpected node site was detected in 9% of patients. The total rate of micrometastasis to the sentinel node was 14.7% but significant differences were observed relative to the melanoma thickness., Conclusions: Preoperative scintigraphy increases the accuracy of sentinel node identification in unusual lymphatic drainage pathways, in unexpected sites and in fast lymphatic drainage. Radioguided biopsy reduces surgical time, requires only local anesthesia and permits shorter hospitalization.

Aims and Background: Sentinel node (SN) biopsy has been introduced to solve the controversy concerning the effectiveness of prophylactic lymphadenectomy in intermediate thickness melanoma. The aim of this study was to evaluate the rate of metastases, the technical details of the procedure, and the main reasons of failure., Methods: 235 patients affected by intermediate thickness melanoma (tumor thickness >0.75 mm and <4 mm) without clinical signs of systemic spread (N0M0) were submitted to sentinel node biopsy between 1996 and 2000. Preoperative lymphoscintigraphy was routinely performed in the last 184 patients. Intraoperative mapping with gamma probe was combined with the use of vital dye for identification of sentinel nodes in the last 113 patients., Results: The SN detection rate was 95.6%, with significant differences depending on the site of dissection and the use of a gamma probe. The overall rate of micrometastases was 14.7%, but relevant differences were recorded between different subgroups of patients (T2, 5.1%; T3a, 19.6%; T3b, 29%)., Conclusions: Sentinel node biopsy requires a multidisciplinary approach (surgery, pathology and nuclear medicine) for reliable results. The association of vital dye and intraoperative gamma probe for sentinel node harvesting has made the procedure more effective, less time-consuming and less invasive. Failures may be due not only to surgical mistakes, but also to improper nuclear medicine procedures or inaccurate histological evaluation of SNs. Methods for histological examination of the SN are still debated and not standardized but promising results have recently been obtained with molecular oncology techniques (RT-PCR).

The article refers to a volume recently issued by the Criminology Department of the National Centre for Prevention and Social Protection, which illustrates the results of some research carried out in order to verify the effects, if any, of the application of the benefits of amnesty and free pardon (not infrequent in the history of Italy) and of the application of the benefits of mercy, on recidivism. Although the research is focused on the formal figures of sentences of punishment, an attempt has been made to reach indicative conclusions based on the behaviour of those to whom these benefits were granted, in order to discover whether their application has reinforced or weakened the crimino-resistance of the subjects. The indications found in the examination lead to the conclusion that those who are predisposed to a certain type of delinquency, greater or lesser, (for example, towards crimes against the patrimony, especially if recidivous) continued to commit crimes at the same rhythm, or even in some cases at a greater rhythm, while those who may have fallen only rarely into crime (particularly women) tended to relapse less into crime. This is the case also with pardon, although in this case the benefit is individualized and conceded generally as a consequence of favourable prognostic evaluations. It is interesting to note that each time a general measure of amnesty or pardon is issued, the percentages of criminality are increased. The article brings these results to the attention of the reader, as material for reflection on the efficacy of reinforcement of the measures of pardon, with respect to the penal system.