ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment.

BACKGROUND: ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to an immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes. METHODS: In this open-label, randomized study, patients with unresectable MPM received intratumoral ONCOS-102 (3×1011 virus particles on days 1, 4, 8, 36, 78, and 120) and pemetrexed plus cisplatin/carboplatin (from day 22), or pemetrexed plus cisplatin/carboplatin alone. The primary endpoint was safety. Overall survival (OS), progression-free survival, objective response rate, and tumor immunologic activation (baseline and day 36 biopsies) were also assessed. RESULTS: In total, 31 patients (safety lead-in: n=6, randomized: n=25) were enrolled. Anemia (15.0% and 27.3%) and neutropenia (40.0% and 45.5%) were the most frequent grade ≥3 adverse events (AEs) in the ONCOS-102 (n=20) and chemotherapy-alone (n=11) cohorts. No patients discontinued ONCOS-102 due to AEs. No statistically significant difference in efficacy endpoints was observed. There was a numerical improvement in OS (30-month OS rate 34.1% vs 0; median OS 20.3 vs 13.5 months) with ONCOS-102 versus chemotherapy alone in chemotherapy-naïve patients (n=17). By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort. Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort. CONCLUSIONS: ONCOS-102 plus pemetrexed and cisplatin/carboplatin was well tolerated by patients with MPM. In injected tumors, ONCOS-102 promoted a proinflammatory environment, including T-cell infiltration, which showed association with survival at month 18.

A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER).

PURPOSE: Image-guided thermal ablation are established treatment options for non-surgical patients with primary and metastatic liver cancers. However, there are limitations with nonuniformity of cancer tissue destruction, heat sink effect and the risk of thermal ablative injury. The current non-thermal ablative techniques have high risk of local recurrence and are not widely adopted. Histotripsy is a treatment technology that destroys targeted tissue under ultrasound visualization via mechanical destruction through the precise application of acoustic cavitation and can offer the potential of non-invasive, non-thermal and non-ionizing radiation cancer treatment. The aim of this multi-centre non-randomized phase I/II trial is to assess the initial safety and efficacy of the prototype investigational 'System' in the treatment of primary and metastatic liver cancers. METHODS/DESIGN: All non-surgical patients with primary/metastatic liver cancers having had previous liver directed therapy, radiation therapy or image-guided ablation may be offered image-guided Histotripsy as per trial protocol. The co-primary endpoints are technical success and procedural safety. Technical success is determined, at ≤ 36 h post procedure, by evaluating the histotripsy treatment size and coverage. The procedural safety is defined by procedure related major complications, defined as Common Terminology Criteria for Adverse Events (CTCAE version 5) grade 3 or higher toxicities, up to 30 days post procedure. This phase I/II trial has intended to recruit up to 45 patients to show safety and efficacy of image-guided histotripsy in liver cancers. TRAIL REGISTRATION: Clinicaltrials.gov identifier-NCT04573881; NIHR CRN CPMS-ID 47572.

First-in-man histotripsy of hepatic tumors: the THERESA trial, a feasibility study.

Rationale Current hepatic locoregional therapies are limited in terms of effectiveness and toxicities. Given promising pre-clinical results, a first in-human trial was designed to assess the technical effectiveness and safety profile of histotripsy, a noninvasive, non-thermal, non-ionizing focused ultrasound therapy that creates precise, predictable tissue destruction, in patients with primary and secondary liver tumors.Methods A multicenter phase I trial (Theresa Study) was performed in a single country with 8 weeks of planned follow-up. Eight of fourteen recruited patients were deemed eligible and enrolled in the study. Hepatic histotripsy, was performed with a prototype system (HistoSonics, Inc., Ann Arbor, MI). Eleven tumors were targeted in the 8 patients who all had unresectable end-stage multifocal liver tumors: colorectal liver metastases (CRLM) in 5 patients (7 tumors), breast cancer metastases in 1 (1 tumor), cholangiocarcinoma metastases in 1 (2 tumors), and hepatocellular carcinoma (HCC) in 1 (1 tumor). The primary endpoint was acute technical success, defined as creating a zone of tissue destruction per planned volume assessed by MRI 1-day post-procedure. Safety (device-related adverse events) through 2 months was a secondary endpoint.Results The 8 patients had a median age of 60.4 years with an average targeted tumor diameter of 1.4 cm. The primary endpoint was achieved in all procedures. The secondary safety profile endpoint identified no device-related adverse events. Two patients experienced a continuous decline in tumor markers during the eight weeks following the procedure.Conclusions This first-in-human trial demonstrates that hepatic histotripsy effectively destroys liver tissue in a predictable manner, correlating very well with the planned histotripsy volume, and has a high safety profile without any device-related adverse events. Based on these results, the need for more definitive clinical trials is warranted. Trial Registration: Study to Evaluate VORTX Rx (Theresa). NCT03741088. https://clinicaltrials.gov/ct2/show/NCT03741088 KEY POINTSHistotripsy, a new noninvasive, non-thermal, non-ionizing focused ultrasound therapy, safely created a zone of tissue destruction in the liver that correlated very well with the pre-defined planned tissue destruction volume.In this first human trial histotripsy was well tolerated with no histotripsy device-related adverse events and its primary endpoint of acute technical success was achieved in all 8 enrolled patients with primary or secondary liver tumors.This new locoregional therapy for patients with liver tumors is safe and effective, warranting further trials.

Muscle Precursor Cells Enhance Functional Muscle Recovery and Show Synergistic Effects With Postinjury Treadmill Exercise in a Muscle Injury Model in Rats.

BACKGROUND: Skeletal muscle injuries represent a major concern in sports medicine. Cell therapy has emerged as a promising therapeutic strategy for muscle injuries, although the preclinical data are still inconclusive and the potential clinical use of cell therapy has not yet been established. PURPOSE: To evaluate the effects of muscle precursor cells (MPCs) on muscle healing in a small animal model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 27 rats were used in the study. MPCs were isolated from rat (n = 3) medial gastrocnemius muscles and expanded in primary culture. Skeletal muscle injury was induced in 24 rats, and the animals were assigned to 3 groups. At 36 hours after injury, animals received treatment based on a single ultrasound-guided MPC (105 cells) injection (Cells group) or MPC injection in combination with 2 weeks of daily exercise training (Cells+Exercise group). Animals receiving intramuscular vehicle injection were used as controls (Vehicle group). Muscle force was determined 2 weeks after muscle injury, and muscles were collected for histological and immunofluorescence evaluation. RESULTS: Red fluorescence-labeled MPCs were successfully transplanted in the site of the injury by ultrasound-guided injection and were localized in the injured area after 2 weeks. Transplanted MPCs participated in the formation of regenerating muscle fibers as corroborated by the co-localization of red fluorescence with developmental myosin heavy chain (dMHC)-positive myofibers by immunofluorescence analysis. A strong beneficial effect on muscle force recovery was detected in the Cells and Cells+Exercise groups (102.6% ± 4.0% and 101.5% ± 8.5% of maximum tetanus force of the injured vs healthy contralateral muscle, respectively) compared with the Vehicle group (78.2% ± 5.1%). Both Cells and Cells+Exercise treatments stimulated the growth of newly formed regenerating muscles fibers, as determined by the increase in myofiber cross-sectional area (612.3 ± 21.4 µm2 and 686.0 ± 11.6 µm2, respectively) compared with the Vehicle group (247.5 ± 10.7 µm2), which was accompanied by a significant reduction of intramuscular fibrosis in Cells and Cells+Exercise treated animals (24.2% ± 1.3% and 26.0% ± 1.9% of collagen type I deposition, respectively) with respect to control animals (40.9% ± 4.1% in the Vehicle group). MPC treatment induced a robust acceleration of the muscle healing process as demonstrated by the decreased number of dMHC-positive regenerating myofibers (enhanced replacement of developmental myosin isoform by mature myosin isoforms) (4.3% ± 2.6% and 4.1% ± 1.5% in the Cells and Cells+Exercise groups, respectively) compared with the Vehicle group (14.8% ± 13.9%). CONCLUSION: Single intramuscular administration of MPCs improved histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries. Cell therapy showed a synergistic effect when combined with an early active rehabilitation protocol in rats, which suggests that a combination of treatments can generate novel therapeutic strategies for the treatment of human skeletal muscle injuries. CLINICAL RELEVANCE: Our study demonstrates the strong beneficial effect of MPC transplant and the synergistic effect when the cell therapy is combined with an early active rehabilitation protocol for muscle recovery in rats; this finding opens new avenues for the development of effective therapeutic strategies for muscle healing and clinical trials in athletes undergoing MPC transplant and rehabilitation protocols.

Association among the R.E.N.A.L. nephrometry score and clinical outcomes in patients with small renal masses treated with percutaneous contrast enhanced ultrasound radiofrequency ablation.

INTRODUCTION: An association between the R.E.N.A.L. nephrometry score (RNS) and clinical outcomes in patients with a small renal mass (SRM) has been proposed. We analyzed clinical outcomes according to the RNS in patients with a SRM treated with percutaneous contrast enhanced ultrasound (CEUS) radiofrequency ablation (RFA). MATERIAL AND METHODS: Patients with a SRM, who underwent RFA between January 2005 and March 2015, were retrospectively identified. The association between RNS and clinical outcomes was evaluated using parametric and non-parametric analysis. RESULTS: We analyzed 163 SRMs in 149 consecutive patients. The mean age was 71.7 years. Mean follow-up time was 33.3 months ±20.6 (2-102). The mean RNS was 5.6 ±1.52 (4-11). A total of 121 (74.2%) cases were of low complexity and 42 (25.8%) were medium complexity. We identified 11 cases of tumor persistence (6.7%). The mean RNS was 5.58 in the cases with no persistence and 5.73 in the cases with persistence (p = 0.788). We identified 15 (9.2%) cases of recurrence. The mean RNS was 5.57 ±0.1 (4-11) in the cases without recurrence and 5.73 ±0.4 (4-9) in recurrence cases (p = 0.804). Of the 76 biopsy proven RCC cases, 8 (10.5%) cases of recurrence were observed, 5 in the low complexity group and 3 in the medium complexity group (p = 0.690). A total of 9 (5.5%) cases of complications were observed, with 5 (4.3%) in the low complexity group and 4 cases in the medium complexity group (p = 0.23). The mean length of stay was 1.5 days with a significant difference between low and medium complexity groups (1.3 vs. 2.1 days, p = 0.02). The mean difference between preoperative eGFR and estimated eGFRat 12 months was -3.08 mL / min ±13.3 (-49.4-34.1) and was significant (p = 0.008).However, this variation did not show significant differences between the low and medium complexity groups (p = 0.936). All-cause mortality was 11.7%, 14 cases (11.6%) in the low complexity group and 5 (11.9%) in the medium complexity group (p = 1.0). No cases of renal cell carcinoma (RCC) specific mortality were identified. CONCLUSIONS: The RNS was not associated with tumor persistence, recurrence, cancer specific mortality, complications or renal function 12 months after the first treatment, showing significant difference only in length of hospital stay between low and medium complexity groups.

Retrospective Study of Cystic Echinococcosis in a Recent Cohort of a Referral Center for Liver Surgery.

BACKGROUND: Cystic echinococcosis (CE) is a zoonosis endemic in Spain caused by the larval stage of the cestode Echinococcus granulosus and is one of the 18 neglected tropical diseases recognized by the WHO. The aim of this study was to describe the epidemiological and clinical data of CE in a surgical referral hospital. METHODS: A retrospective descriptive study of all adults' patients diagnosed with CE and followed at Vall d'Hebron University Hospital in Barcelona, Spain, between 2000 and 2015. RESULTS: We found 151 cases, 78 (51.7%) women, and median age at diagnosis was 68 (range, 15-92) years. Diagnosis was a radiological finding in 97 (64.2%) and the most frequent location was the liver [135 (89.4%) patients]. Nearly 80% of the cysts were calcified and serology was positive in 48 (51.6%). The WHO-IWGE classification was only available in 70 of the 104 (67.3%) cases of liver cysts that had an ultrasound. First therapeutic plan was "watch and wait" followed by surgery. International recommendations were not always followed, particularly in CE4 and CE5 stages, and 20% needed a change of treatment because of progression or recurrence. Patients treated surgically were younger, more symptomatic, and had larger and less calcified cysts in multiple sites. Serology was not useful for CE diagnosis and neither serology nor calcification of the cyst helped to predict viability. CONCLUSIONS: The formation of multidisciplinary teams in reference hospitals could help to improve CE diagnosis, its management, and follow-up, since international recommendations are not usually followed.

Ultrasound Evolution of Pediatric Urinary Schistosomiasis after Treatment with Praziquantel in a Highly Endemic Area.

Urinary schistosomiasis causes damage to the urological system. Ultrasound is a method that detects the burden of secondary disease, individually and in epidemiological studies. In this study, the Schistosoma haematobium-associated urinary tract pathology is analyzed before and after treatment in a short period of time. Seventy children who had previously participated in an epidemiological study on schistosomiasis in the city of Cubal, Angola, and had also performed urinary ultrasound between August 2013 and February 2014 were cited 6-8 months later to assess the possible reinfection and repeat new urinary ultrasound, analyzing changes at the level of urinary pathology. The presence of hematuria and proteinuria was also analyzed. Of the 70 children analyzed, 29 (41.4%) were girls, with an average age of 10.4 years (standard deviation 2.3). Fifty-three (75.7%) had an improvement in their bladder and/or kidney scores, whereas 12 (17.1%) had no change and five (7.1%) had progression of the disease. None of the parameters analyzed completely disappeared. After one single course of treatment with praziquantel, all the analyzed parameters showed regression. Improvement was greater in the urinary bladder than in the upper urinary tract, though these lesions also reversed; the reversion of all parameters was greater among children older than 10 years old than the younger ones. Proteinuria was the parameter with a smaller reduction. Ultrasound should be a usual tool for diagnosis and follow-up in urinary schistosomiasis, particularly in children; more accurate recommendations about follow-up in the case of children whose lesions do not reverse should be established.

Ultrasound findings and associated factors to morbidity in Schistosoma haematobium infection in a highly endemic setting.

OBJECTIVE: To evaluate the usefulness of the WHO classification of ultrasound pathological changes and to establish risk factors for morbidity in a highly endemic setting. METHODS: One hundred and fifty-seven ultrasounds were performed on school-aged children previously diagnosed with urinary schistosomiasis in Cubal, Angola. The findings were analysed according to the WHO guidelines. Factors for morbidity were studied. RESULTS: Mean age of the children was 8.7 (SD 3.2) years. Pathological changes were found in 85.3% (84.7% in the bladder, 34.4% the ureter and 6.3% kidney lesions). The global score according to the WHO classification was 5.74. Male gender [OR 2.61 (1.04-6.58); P 0.043] and older age [OR 2.96 (1.17-7.46); P 0.023] were associated with a higher risk of developing any kind of urinary abnormality. Proteinuria was present in 61.7% of the children. Macroscopic haematuria [OR 2.48 (1.11-5.58); P = 0.02)] and a high level of proteinuria > 300 mg/dl [OR 5.70 (2.17-14.94); P 300 mg/dl)] were associated with abnormalities of the upper urinary tract and showed good positive and negative predictive values for the detection of pathology in the upper urinary tract (65.5% and 71.1%, respectively). CONCLUSIONS: Severe urinary tract pathology was found in a high percentage of the children in our setting. Microhaematuria and proteinuria were good markers of morbidity, proteinuria being more precise for severe alterations of the upper urinary tract. We suggest initial and evolutive ultrasound in children diagnosed with schistosomiasis, and close monitoring including periodic controls. As schistosomiasis control efforts are currently focused on reducing morbidity, tests that detect the presence or degree of morbidity are essential for targeting treatment and tracking the progress of control campaigns.

Biopsia selectiva del ganglio centinela en el carcinoma papilar de tiroides en pacientes sin evidencia preoperatoria de metástasis ganglionar / Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis

Introducción: La linfadenectomía en la cirugía del carcinoma papilar de tiroides se aconseja cuando hay evidencia de metástasis ganglionar cervical (terapéutica) o en pacientes de alto riesgo (profiláctica), como en los tumores T3 y T4 de la clasificación TNM. La técnica de la biopsia selectiva del ganglio centinela puede mejorar el diagnóstico prequirúrgico de las metástasis ganglionares. Objetivo: Analizar el resultado de la biopsia selectiva del ganglio centinela en un grupo de pacientes con carcinoma papilar de tiroides T sin evidencia de afectación ganglionar antes de la cirugía. Pacientes y método: Estudio retrospectivo, unicéntrico en el que se incluyeron los pacientes intervenidos entre los años 2011-2013 que fueran clínicamente N0. La identificación del ganglio centinela se realizó mediante técnica isotópica. En todos los casos, se practicó linfadenectomía del compartimento afecto si el ganglio centinela era positivo, y del compartimento central en caso de ganglio centinela negativo. Resultados: Se incluyeron 43 pacientes, 34 mujeres, con una edad media de 52,3 (±17) años. De los 170 ganglios centinela resecados, 46 (27%) fueron positivos para metástasis, que correspondían a 24 (55,8%) pacientes. En las linfadenectomías se resecaron 612 ganglios. De ellos, 96 (15,6%) fueron positivos para metástasis. Doce de los treinta (40%) pacientes cT1N0 y cT2N0 pasaron a pN1 tras la biopsia selectiva del ganglio centinela, mientras que 12 de los 13 (92%) pacientes cT3N0 y cT4N0, acabaron siendo pN1. Conclusiones: La biopsia selectiva del ganglio centinela recalifica más del 50% de pacientes de cN0 a pN1. Se confirma la necesidad de vaciamiento ganglionar en los tumores T3 y T4, pero pone al descubierto la presencia de metástasis linfáticas en el 40% de los T1-T2 (AU)

Introduction: Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. Objective: To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. Patients and method: A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. Results: Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. Conclusions: Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors (AU)

Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis. / Biopsia selectiva del ganglio centinela en el carcinoma papilar de tiroides en pacientes sin evidencia preoperatoria de metástasis ganglionar.

INTRODUCTION: Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. OBJECTIVE: To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. PATIENTS AND METHOD: A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. RESULTS: Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. CONCLUSIONS: Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors.

Postinjury Exercise and Platelet-Rich Plasma Therapies Improve Skeletal Muscle Healing in Rats But Are Not Synergistic When Combined.

BACKGROUND: Skeletal muscle injuries are the most common sports-related injury and a major concern in sports medicine. The effect of platelet-rich plasma (PRP) injections on muscle healing is still poorly understood, and current data are inconclusive. PURPOSE: To evaluate the effects of an ultrasound-guided intramuscular PRP injection, administered 24 hours after injury, and/or posttraumatic daily exercise training for 2 weeks on skeletal muscle healing in a recently established rat model of skeletal muscle injury that highly mimics the muscle trauma seen in human athletes. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 40 rats were assigned to 5 groups. Injured rats (medial gastrocnemius injury) received a single PRP injection (PRP group), daily exercise training (Exer group), or a combination of a single PRP injection and daily exercise training (PRP-Exer group). Untreated and intramuscular saline-injected animals were used as controls. Muscle force was determined 2 weeks after muscle injury, and muscles were harvested and evaluated by means of histological assessment and immunofluorescence microscopy. RESULTS: Both PRP (exhibiting 4.8-fold higher platelet concentration than whole blood) and exercise training improved muscle strength (maximum tetanus force, TetF) in approximately 18%, 20%, and 30% of rats in the PRP, PRP-Exer, and Exer groups, respectively. Specific markers of muscle regeneration (developmental myosin heavy chain, dMHC) and scar formation (collagen I) demonstrated the beneficial effect of the tested therapies in accelerating the muscle healing process in rats. PRP and exercise treatments stimulated the growth of newly formed regenerating muscle fibers (1.5-, 2-, and 2.5-fold increase in myofiber cross-sectional area in PRP, PRP-Exer, and Exer groups, respectively) and reduced scar formation in injured skeletal muscle (20%, 34%, and 41% of reduction in PRP, PRP-Exer, and Exer groups, respectively). Exercise-treated muscles (PRP-Exer and Exer groups) had significantly reduced percentage of dMHC-positive regenerating fibers (35% and 47% decrease in dMHC expression, respectively), indicating that exercise therapies accelerated the muscle healing process witnessed by the more rapid replacement of the embryonic-developmental myosin isoform by mature muscle myosin isoforms. CONCLUSION: Intramuscular PRP injection and, especially, treadmill exercise improve histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries in athletes. However, there was not a synergistic effect when both treatments were combined, suggesting that PRP does not add any beneficial effect to exercise-based therapy in the treatment of injured skeletal muscle. CLINICAL RELEVANCE: This study demonstrates the efficacy of an early active rehabilitation protocol or single intramuscular PRP injection on muscle recovery. The data also reveal that the outcome of the early active rehabilitation is adversely affected by the PRP injection when the two therapies are combined, and this could explain why PRP therapies have failed in randomized clinical trials where the athletes have adhered to postinjection rehabilitation protocols based on the principle of early, active mobilization.

Múltiples quistes parapiélicos en la enfermedad de Fabry / Multiple parapelvic cysts in Fabry disease

La enfermedad de Fabry es una enfermedad de depósito lisosomal de carácter hereditario, ligada al cromosoma X, causado por el déficit de la enzima alfa-galactosidasa A (alfa-GLA A), lo que conduce a la acumulación de glicoesfingolípidos, principalmente globotriaosilceramida, en los tejidos. Es una enfermedad poco prevalente, y con muy bajo índice de sospecha, por lo que, generalmente, existe un retraso en el diagnóstico y en el tratamiento. Presentamos un caso de un paciente varón afecto de la enfermedad de Fabry, que presentaba múltiples quistes parapiélicos e insuficiencia renal, sin presentar angioqueratomas. El estudio genético mostró una mutación en el gen de alfa-GLA A que no ha sido descrita previamente en el registro de mutaciones, y de novo, ya que no se encontró en otros familiares, además que no fue trasmitida a la descendencia. La presencia de múltiples quistes parapiélicos y su peculiar aspecto fue lo que hizo sospechar el diagnóstico de la enfermedad (AU)

Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis (AU)

Multiple parapelvic cysts in Fabry disease. / Múltiples quistes parapiélicos en la enfermedad de Fabry.

Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis.

Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study.

BACKGROUND & AIMS: Detecting portal hypertension (PH) before the development of varices is important for prognosis and for designing interventional studies. None of the available strategies is used in practice. We evaluated a sequential screening-diagnostic strategy based on clinical data and transient elastography (TE) to detect PH in asymptomatic outpatients with liver disease. METHODS: Consecutive patients with chronic liver disease and no previous diagnosis of PH were screened by TE. Patients with liver stiffness (LS) ⩾ 13.6 kPa were further evaluated by endoscopy and hepatic venous pressure gradient (HVPG). For analysis, patients were classified in 3 groups: group A, platelets ⩾ 150,000/mm(3), normal abdominal ultrasound; group B, platelets <150,000/mm(3), normal ultrasound; group C, platelets <150,000/mm(3), abnormal ultrasound (splenomegaly, nodular liver surface). RESULTS: 250 patients were evaluated (69% group A, 20% group B, 11% group C). In 9% elastography was non-valid. LS ⩾ 13.6 was found in 54 patients (8% A, 43% B, and 81% C, p<0.001). Endoscopy was performed in 49 of these: 20% had small varices, 0% high-risk varices. No patients from group A had varices, and 90% with varices belonged to group C. HVPG was obtained in 40 patients: 93% had PH (HVPG >5 mmHg) and 65% clinically significant PH (CSPH, HVPG ⩾ 10). Only 3 patients, all from group A, had HVPG <5. All patients from groups B and C with LS ⩾ 13.6 had PH. The LS 25 cut-off was excellent at ruling-in CSPH. CONCLUSIONS: A simple strategy based on routine clinical data and TE could be useful to detect early PH among asymptomatic patients with chronic liver disease.

SPECT/CT sentinel lymph node identification in papillary thyroid cancer: lymphatic staging and surgical management improvement.

PURPOSE: Lymphadenectomy in papillary thyroid carcinoma (PTC) continues to be controversial. A better staging method is needed to provide adequate individual surgical treatment. SPECT/CT lymphoscintigraphy and sentinel lymph node (SLN) biopsy may improve lymphatic staging and surgical treatment. Our main objectives were to describe the lymphatic drainage of PTC using lymphoscintigraphy, to evaluate the lymphatic spread (comparing SLN and lymphadenectomy results) and to analyse the impact of SLN identification in surgery. METHODS: We prospectively studied 24 consecutive patients with PTC (19 women; mean age 52.7 years, range 22-81 years). The day before surgery, lymphoscintigraphy with ultrasound-guided intratumoral injection ((99m)Tc-nanocolloid, 148 MBq) was performed, obtaining planar and SPECT/CT images. All patients underwent total thyroidectomy, SLN biopsy (hand-held gamma probe) with perioperative analysis, central compartment node dissection, or laterocervical lymphadenectomy if perioperative stage N1b or positive SLNs in this lymphatic basin. RESULTS: Lymphoscintigraphy revealed at least one SLN in 19 of 24 patients (79 %) on planar and SPECT/CT images, and in 23 of 24 patients (96 %) during surgery using a hand-held gamma probe. Lymph node metastases were detected with classical perioperative techniques (ultrasound guidance and surgical inspection) in 3 of 24 patients, by perioperative SLN analysis in 10 of 23, and by definitive histology in 13 of 24. The false-negative (FN) ratio for SLN was 7.7 % (one patient with bulky lymph nodes). The FN ratio for perioperative frozen sections was 15.4 % (two patients, one with micrometastases, the other with bilateral SLN). Lymphatic drainage was only to the central compartment in 6 of 24 patients (3 of the 6 with positive SLNs for metastases), only to the laterocervical basin in 5 of 24 patients (all unilateral, 2 of 5 positive SLNs) and to the central and laterocervical compartments in 12 of 24 patients (6 of 12 and 3 of 12 positive SLNs, respectively). CONCLUSION: Lymphoscintigraphy reveals the lymph node drainage in a high proportion of patients. It detects laterocervical drainage in a significant percentage of patients, allowing the detection of occult lymph node metastases and improving the surgical management in PTC.