Circulating Total Extracellular Vesicles Cargo Are Associated with Age-Related Oxidative Stress and Susceptibility to Cardiovascular Diseases: Exploratory Results from Microarray Data.

Aging is a risk factor for many non-communicable diseases such as cardiovascular and neurodegenerative diseases. Extracellular vesicles and particles (EVP) carry microRNAs that may play a role in age-related diseases and may induce oxidative stress. We hypothesized that aging could impact EVP miRNA and impair redox homeostasis, contributing to chronic age-related diseases. Our aims were to investigate the microRNA profiles of circulating total EVPs from aged and young adult animals and to evaluate the pro- and antioxidant machinery in circulating total EVPs. Plasma from 3- and 21-month-old male Wistar rats were collected, and total EVPs were isolated. MicroRNA isolation and microarray expression analysis were performed on EVPs to determine the predicted regulation of targeted mRNAs. Thirty-one mature microRNAs in circulating EVPs were impacted by age and were predicted to target molecules in canonical pathways directly related to cardiovascular diseases and oxidative status. Circulating total EVPs from aged rats had significantly higher NADPH oxidase levels and myeloperoxidase activity, whereas catalase activity was significantly reduced in EVPs from aged animals. Our data shows that circulating total EVP cargo-specifically microRNAs and oxidative enzymes-are involved in redox imbalance in the aging process and can potentially drive cardiovascular aging and, consequently, cardiac disease.

Supramolecular assemblies from antimony(V) complexes for the treatment of leishmaniasis.

The pentavalent meglumine antimoniate (MA) is still a first-line drug in the treatment of leishmaniasis in several countries. As an attempt to elucidate its mechanism of action and develop new antimonial drugs with improved therapeutic profile, Sb(V) complexes with different ligands, including ß-cyclodextrin (ß-CD), nucleosides and non-ionic surfactants, have been studied. Interestingly, Sb(V) oxide, MA, its complex with ß-CD, Sb(V)-guanosine complex and amphiphilic Sb(V) complexes with N-alkyl-N-methylglucamide, have shown marked tendency to self-assemble in aqueous solutions, forming nanoaggregates, hydrogel or micelle-like nanoparticles. Surprisingly, the resulting assemblies presented in most cases slow dissociation kinetics upon dilution and a strong influence of pH, which impacted on their pharmacokinetic and therapeutic properties against leishmaniasis. To explain this unique property, we raised the hypothesis that multiple pnictogen bonds could contribute to the formation of these assemblies and their kinetic of dissociation. The present article reviews our current knowledge on the structural organization and physicochemical characteristics of Sb-based supramolecular assemblies, as well as their pharmacological properties and potential for treatment of leishmaniasis. This review supports the feasibility of the rational design of new Sb(V) complexes with supramolecular assemblies for the safe and effective treatment of leishmaniasis.

Nanoassemblies from Amphiphilic Sb Complexes Target Infection Sites in Models of Visceral and Cutaneous Leishmaniases.

This work aims to evaluate whether nanoassemblies (NanoSb) made from antimony(V) complexes with octanoyl-N-methylglucamide (SbL8) or decanoyl-N-methylglucamide (SbL10) would effectively target the infection sites in visceral and cutaneous leishmaniases (VL and CL). NanoSb were investigated regarding stability at different pHs, accumulation of Sb in the macrophage host cell and liver, and in vitro and in vivo activities in models of leishmaniasis. The kinetic stability assay showed that NanoSb are stable at neutral pH, but release incorporated lipophilic substance after conformational change in media that mimic the gastric fluid and the parasitophorous vacuole. NanoSb promoted greater accumulation of Sb in macrophages and in the liver of mice after parenteral administration, when compared to conventional antimonial Glucantime®. SbL10 was much more active than Glucantime® against intramacrophage Leishmania amastigotes and less cytotoxic than SbL8 against macrophages. The in vitro SbL10 activity was further enhanced with co-incorporated miltefosine. NanoSb showed high antileishmanial activity in the L. donovani murine VL after parenteral administration and moderate activity in the L. amazonensis murine CL after topical treatment. This study supports the ability of NanoSb to effectively deliver a combination of Sb and co-incorporated drug to host cell and infected tissues, in a better way than Glucantime® does.

Formulation of Amphotericin B in PEGylated Liposomes for Improved Treatment of Cutaneous Leishmaniasis by Parenteral and Oral Routes.

Liposomal amphotericin B (AmB) or AmBisome® is the most effective and safe therapeutic agent for visceral leishmaniasis (VL), but its clinical efficacy is limited in cutaneous leishmaniasis (CL) and HIV/VL co-infection. The aim of this work was to develop a formulation of AmB in PEGylated liposomes and compare its efficacy to AmBisome® in a murine model of CL. Formulations of AmB in conventional and PEGylated liposomes were characterized for particle size and morphology, drug encapsulation efficiency and aggregation state. Those were compared to AmBisome® in Leishmania amazonensis-infected BALB/c mice for their effects on the lesion size growth and parasite load. The conventional and PEGylated formulations showed vesicles with 100-130 nm diameter and low polydispersity, incorporating more than 95% of AmB under the non-aggregated form. Following parenteral administration in the murine model of CL, the PEGylated formulation of AmB significantly reduced the lesion size growth and parasite load, in comparison to control groups, in contrast to conventional liposomal AmB. The PEGylated formulation of AmB was also effective when given by oral route on a 2-day regimen. This work reports for the first time that PEGylated liposomal AmB can improve the treatment of experimental cutaneous leishmaniasis by both parenteral and oral routes.

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations.

The liposomal amphotericin B (AmB) formulation, AmBisome®, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, its clinical efficacy depends on the patient's immunological status, the clinical manifestation and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. This review reports the progress achieved thus far toward the understanding of the mechanism responsible for the reduced toxicity of liposomal AmB formulations and the factors that influence their efficacy against leishmaniasis. It also presents the recent advances in the development of more effective liposomal AmB formulations, including topical and oral liposome formulations. The critical role of the AmB aggregation state and release rate in the reduction of drug toxicity and in the drug efficacy by non-invasive routes is emphasized. This paper is expected to guide future research and development of innovative liposomal formulations of AmB.

Antileishmanial activity of fullerol and its liposomal formulation in experimental models of visceral leishmaniasis.

Visceral leishmaniasis (VL) is a systemic parasitic disease that leads to high rates of morbidity and mortality in humans worldwide. There is a great need to develop new drugs and novel strategies to make chemotherapy for this disease more efficacious and well tolerated. Recent reports on the immunomodulatory effects and the low toxicity of the spherical carbon nanostructure fullerol led us to investigate in vitro and in vivo antileishmanial activity in free and encapsulated forms in liposomes. When assayed against intramacrophagic Leishmania amastigotes, fullerol showed a dose-dependent reduction of the infection index with IC50 of 0.042 mg/mL. When given daily by i.p. route for 20 days (0.05 mg/kg/d) in a murine model of acute VL, fullerol promoted significant reduction in the liver parasite load. To improve the delivery of fullerol to the infection sites, liposomal formulations were prepared by the dehydration-rehydration method. When evaluated in the acute VL model, liposomal fullerol (Lip-Ful) formulations given i.p. at 0.05 and 0.2 mg/kg with 4-days intervals were more effective than the free form, with significant parasite reductions in both liver and spleen. Lip-Ful at 0.2 mg/kg promoted complete parasite elimination in the liver. The antileishmanial activity of Lip-Ful was further confirmed in a chronic model of VL. Lip-Ful was also found to induce secretion of pro-inflammatory TNF-α, IFN-γ and IL-1ß cytokines. In conclusion, this work reports for the first time the antileishmanial activity of fullerol and introduces an innovative approach for treatment of VL based on the association of this nanostructure with liposomes.

Consenso sobre la biopsia selectiva del ganglio centinela en el cáncer de mama. Revisión 2013 de la Sociedad Española de Senología y Patología Mamaria / Consensus on sentinel lymph node biopsy in breast cancer. Review of the Spanish Society of Senology and Breast Pathology 2013

La biopsia selectiva del ganglio centinela es una técnica diagnóstica aceptada como el procedimiento de elección para la estadificación axilar del cáncer de mama. En este documento, correspondiente a la última Reunión de Consenso celebrada en Valencia y organizada por la Sociedad Española de Senología y Patología Mamaria, se actualizan los consensos previos y se reflejan las conclusiones acerca de las últimas propuestas en el manejo del ganglio centinela en el cáncer de mama (AU)

Sentinel lymph node biopsy is currently a widely accepted diagnostic technique and is the procedure of choice for axillary staging of breast cancer. In this article, following the latest Consensus Meeting held in Valencia organized by the Spanish Society of Senology and Breast Pathology, previous consensus are updated. Also discussed are conclusions related to the latest trends in the management of the sentinel node in breast cancer (AU)

Consenso sobre la biopsia selectiva del ganglio centinela en el cáncer de mama. Revisión 2013 de la Sociedad Española de Senología y Patología Mamaria / Consensus on sentinel lymph node biopsy in breast cancer. Review of the Spanish Society of Senology and Breast Pathology 2013

La biopsia selectiva del ganglio centinela es una técnica diagnóstica aceptada como el procedimiento de elección para la estadificación axilar del cáncer de mama. En este documento, correspondiente a la última Reunión de Consenso celebrada en Valencia y organizada por la Sociedad Española de Senología y Patología Mamaria, se actualizan los consensos previos y se reflejan las conclusiones acerca de las últimas propuestas en el manejo del ganglio centinela en el cáncer de mama

Sentinel lymph node biopsy is currently a widely accepted diagnostic technique and is the procedure of choice for axillary staging of breast cancer. In this article, following the latest Consensus Meeting held in Valencia organized by the Spanish Society of Senology and Breast Pathology, previous consensus are updated. Also discussed are conclusions related to the latest trends in the management of the sentinel node in breast cancer

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

CONTEXT: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. OBJECTIVE: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). RESULTS: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon-induced thyroiditis.

OBJECTIVE: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT. DESIGN, PATIENTS AND METHODS: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT). RESULTS: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV. CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.

Estudio mediante linfogammagrafía isotópica del edema postquirúrgico tras cirugía del sector fémoro-poplíteo / Lymphoscintigraphy study of oedema after femoropopliteal segment surgery

Introducción: El edema postcirugía del sector femoropoplíteo es una complicación frecuente, no relacionada con la gravedad de los síntomas previos ni con los cambios en la PA distal posterior. El objetivo del estudio es evaluar si el edema observado en los pacientes intervenidos de bypass femoropoplíteo es de causa linfática, y la posible influencia del tipo de prótesis utilizada y del tipo de intervención. Pacientes y métodos: Estudio analítico observacional de casos control con 30 pacientes intervenidos de bypass femoropoplíteo. Se ha realizado linfogammagrafía isotópica del sistema linfático superficial y profundo de ambas extremidades en todos los pacientes seleccionados para el estudio. Resultados: Se utilizó vena safena en 19 pacientes y PTFE en 11. Quince pacientes fueron controles (sin edema) y 15 casos (con edema). Tipo de cirugía: 9 reconstrucciones a primera porción de poplítea (1.a p.p.), 18 a tercera porción de poplítea (3.a p.p.) y 3 a ramas distales. Hallazgos gammagráficos: en las 30 exploraciones se observó asimetría del drenaje linfático entre las 2 extremidades, excepto en 1 caso (que no presentó edema). En 5 no había drenaje linfático (uno desarrolló edema). Se compararon casos con controles y pacientes con injerto autólogo y sintético, así como derivaciones por encima y por debajo de la rodilla. La única significación estadística que se obtuvo fue que estos últimos desarrollaron edema con mayor frecuencia que los practicados proximalmente a la rodilla. Conclusión: Por tanto los hallazgos linfogammagráficos no apuntan al daño linfático como causa del edema postcirugía femoropoplítea. Tampoco el material utilizado parece tener influencia. Las derivaciones infrageniculares sufren más edema que las suprageniculares (AU)

Introduction: Post-surgical oedema of the femoropopliteal segment is a frequent complication, unrelated to the severity of the previous symptoms or changes in subsequent distal arterial pressure. The aim of the study is to assess whether the oedema present in femoropopliteal bypass patients is of lymphatic origin, and the possible influence of the prosthesis and the type of intervention used. Patients and methods: An analytical, observational and case-control study of 30 patients who had a femoropopliteal bypass. Isotopic lymphoscintigraphy of the superficial and deep lymphatic system was performed on both limbs in all patients selected for the study. Results: The saphenous vein was used in 19 patients and PTFE in 11. The patients were divided into controls, 15 without oedema, and cases, 15 with oedema. Surgery technique: 9 reconstructions of the popliteal portion (1st p.p.), 18 third popliteal portion (3rd p.p.), and 3 distal branches. Scintigraphy findings: Asymmetric lymphatic drainage between the 2 limbs was observed in the all 30 examinations, except 1 case (which did not have oedema). There was no lymphatic drainage in 5 cases (one developed oedema). Cases with controls and patients with an autologous or synthetic graft, as well as shunts above and below the knee, were compared. The only statistical difference obtained was that the latter developed oedema more often than those performed close to the knee. Conclusions: Therefore, the scintigraphy findings did not point to lymphatic damage as a cause of post-femoropopliteal surgery oedema. The material used did not appear to influence this. The below-knee shunts suffered more oedema than those above the knee (AU)

[Lymphoscintigraphy study of oedema after femoropopliteal segment surgery]. / Estudio mediante linfogammagrafía isotópica del edema postquirúrgico tras cirugía del sector fémoro-poplíteo.

INTRODUCTION: Post-surgical oedema of the femoropopliteal segment is a frequent complication, unrelated to the severity of the previous symptoms or changes in subsequent distal arterial pressure. The aim of the study is to assess whether the oedema present in femoropopliteal bypass patients is of lymphatic origin, and the possible influence of the prosthesis and the type of intervention used. PATIENTS AND METHODS: An analytical, observational and case-control study of 30 patients who had a femoropopliteal bypass. Isotopic lymphoscintigraphy of the superficial and deep lymphatic system was performed on both limbs in all patients selected for the study. RESULTS: The saphenous vein was used in 19 patients and PTFE in 11. The patients were divided into controls, 15 without oedema, and cases, 15 with oedema. Surgery technique: 9 reconstructions of the popliteal portion (1st p.p.), 18 third popliteal portion (3rd p.p.), and 3 distal branches. Scintigraphy findings: Asymmetric lymphatic drainage between the 2 limbs was observed in the all 30 examinations, except 1 case (which did not have oedema). There was no lymphatic drainage in 5 cases (one developed oedema). Cases with controls and patients with an autologous or synthetic graft, as well as shunts above and below the knee, were compared. The only statistical difference obtained was that the latter developed oedema more often than those performed close to the knee. CONCLUSIONS: Therefore, the scintigraphy findings did not point to lymphatic damage as a cause of post-femoropopliteal surgery oedema. The material used did not appear to influence this. The below-knee shunts suffered more oedema than those above the knee.

Is it possible to refine the indication for sentinel node biopsy in high-risk ductal carcinoma in situ?

BACKGROUND: The indication for sentinel node biopsy (SNB) has not been fully established yet for patients with ductal carcinoma in situ (DCIS). AIM: To relate the conversion rate to invasive carcinoma with sentinel node positivity in high risk DCIS, and to refine the clinical presentation analysis in order to better select patients for SNB. For this purpose, a risk score was devised. METHODS: From 1998 to 2005, 151 high-risk DCIS patients from six clinical centres were included in a prospective sentinel node database. The conversion rate to invasive carcinoma was 39%. Ten of 142 (7%) successful SNBs showed a positive sentinel node (eight micrometastatic). The sentinel node was positive in 1% of pure DCIS, in 5.5% of DCIS with micro-invasion, and in 19.5% of invasive carcinoma. RESULTS: Both clinical presentation and corresponding risk score were closely related to conversion to invasive carcinoma. The association of risk score and sentinel node positivity approached but did not reach statistical significance (P=0.06); therefore a subset of further selected higher risk patients could not be defined. CONCLUSION: The relevance of SNB positivity cannot be overlooked in high-risk DCIS patients, however, because SNB is not free from morbidity and cost, more studies are needed to refine its final indication.

Radiolocalización de lesiones mamarias no palpables combinada con la biopsia del ganglio centinela en mujeres con cáncer de mama / Radio-guided occult lesion localization combined with sentinel node biopsy in women with breast cancer

Introducción. La modalidad intralesional de inyección de los radiocoloides en la biopsia del ganglio centinela (BGC) permite la localización de tumores mamarios primitivos no palpables, en un mismo acto quirúrgico, mediante la técnica conocida como ROLL. Pacientes y método. Presentamos nuestra experiencia con la combinación de ambas técnicas (BGC y ROLL). Se analizó retrospectivamente a 233 pacientes: en 65 pacientes se practicó ROLL y en 168 la lesión fue localizada mediante la inserción de guías metálicas (grupo control). Ambos grupos eran comparables en cuanto a sus variables anatomorradiológicas. Resultados. La resección de la lesión se llevó a cabo en un solo tiempo en 169 pacientes. No se observaron diferencias significativas entre ambos grupos en cuanto a la afección de los márgenes quirúrgicos (márgenes correctos del 80% con ROLL frente al 69,9% sin ROLL) ni en el diámetro máximo de la pieza (6,85 frente a 6,52 cm, respectivamente). Conclusión. En pacientes sometidas a la BGC con lesiones mamarias no palpables, la técnica ROLL es una alternativa a las guías metálicas que ofrece una mayor facilidad para la exéresis y más comodidad para la paciente (AU)

Introduction. The practice of intratumoral radiocolloid injection for sentinel node biopsy (SNB) allows localization of nonpalpable breast tumors in the same surgical intervention, using the technique known as radio-guided occult lesion localization (ROLL). Patients and method. We present our experience with the combined use of both techniques (SNB and ROLL). A total of 233 patients were retrospectively analyzed: 65 patients underwent ROLL and 168 patients underwent wire-guided localization (control group) as the excision modality. Both groups had comparable pathologic and radiologic features. Results. Complete excision of the lesion was achieved at the first attempt in only 169 patients. There were no significant differences among groups in surgical margin status (margins were adequate in 80% of ROLL patients vs 69.9% of non-ROLL patients) or in maximum specimen diameter (6.85 cm vs 6.52 cm, respectively). Conclusion. We conclude that ROLL is an acceptable alternative to wire-guided localization in patients with nonpalpable breast tumors undergoing SNB, leading to easier lesion excision and greater patient comfort (AU)

[Radio-guided occult lesion localization combined with sentinel node biopsy in women with breast cancer]. / Radiolocalización de lesiones mamarias no palpables combinada con la biopsia del ganglio centinela en mujeres con cáncer de mama.

INTRODUCTION: The practice of intratumoral radiocolloid injection for sentinel node biopsy (SNB) allows localization of nonpalpable breast tumors in the same surgical intervention, using the technique known as radio-guided occult lesion localization (ROLL). PATIENTS AND METHOD: We present our experience with the combined use of both techniques (SNB and ROLL). A total of 233 patients were retrospectively analyzed: 65 patients underwent ROLL and 168 patients underwent wire-guided localization (control group) as the excision modality. Both groups had comparable pathologic and radiologic features. RESULTS: Complete excision of the lesion was achieved at the first attempt in only 169 patients. There were no significant differences among groups in surgical margin status (margins were adequate in 80% of ROLL patients vs 69.9% of non-ROLL patients) or in maximum specimen diameter (6.85 cm vs 6.52 cm, respectively). CONCLUSION: We conclude that ROLL is an acceptable alternative to wire-guided localization in patients with nonpalpable breast tumors undergoing SNB, leading to easier lesion excision and greater patient comfort.

[Sentinel node biopsy in patients with oral cancer: a pilot study]. / Biopsia selectiva del ganglio centinela en pacientes con carcinoma oral: estudio piloto.

BACKGROUND AND OBJECTIVE: Sentinel node (SN) biopsy represents an alternative to full lymph node dissection in the surgical treatment of several malignant tumors. PATIENTS AND METHOD: Prospective study of 32 consecutive patients with clinically node-negative oral cancer comparing SN biopsy results with standard neck dissection. RESULTS: An effective SN localization was achieved in 31 patients (97%) and a complete agreement with neck dissection was observed: 16 were true negative and 15 were true positive. In 11 out of the 15 positive cases, the SN was the only node containing metastasis (73%). CONCLUSION: SN biopsy predicts the subclinical lymph node status in oral cancer patients.

Biopsia selectiva del ganglio centinela en pacientes con carcinoma oral: estudio piloto / Sentinel node biopsy in patients with oral cancer: a pilot study

FUNDAMENTO Y OBJETIVO: La técnica del ganglio centinela (GC) aparece como una alternativa a la linfadenectomía completa en el tratamiento quirúrgico de diversos tumores. PACIENTES Y MÉTODO: Estudio piloto sobre 32 pacientes consecutivos con cáncer oral clínicamente N0, en los que la biopsia del GC fue comparada con los resultados del vaciamiento cervical. RESULTADOS: La localización del GC fue posible en 31 de los 32 casos (97 por ciento) y mostró una concordancia total con el vaciamiento cervical: 16 verdaderos negativos y 15 verdaderos positivos. Entre los 15 casos positivos, el GC fue el único ganglio afectado en 11 (73 por ciento). CONCLUSIÓN: La biopsia del GC es una técnica capaz de predecir el estado de diseminación linfática subclínica en el cáncer oral (AU)

Internal mammary sentinel node metastases in an otherwise lymph-node negative breast cancer patient.

A 35 year old woman with biopsy proved breast cancer was submitted for sentinel node (SN) biopsy. Preoperative lymphoscintigraphy displayed both axillary and internal mammary (IM) uptake foci consistent with SNs. Full axillary dissection was completed because of a greater-than 2 cm primary lesion. Two axillary SNs were excised. An IM SN was also excised through the second intercostal space, with the aid of the gamma probe. Fourteen axillary nodes, including SNs, were negative, whereas the IM SN harbored several metastatic implants. Implications for staging, prognosis and further therapy of such IM-only positive sentinel nodes are discussed.