Contralateral Axillary Lymph Node Metastases from Breast Carcinoma: Is it Time to Review TNM Cancer Staging?

BACKGROUND: Contralateral axillary lymph node metastasis (CAM) is an infrequent clinical condition currently considered an M1, stage IV, disease. Due to the absence of shared data on CAM significance and on its therapeutic approach, be it curative or simply palliative, its management is still uncertain and undoubtedly represents a clinical challenge. PATIENTS AND METHODS: Patients with pathologically confirmed metachronous CAM were retrospectively evaluated. All patients had been managed at the European Institute of Oncology, Milan, Italy, from 1997. Patients with distant metastases at the time of CAM were excluded. Possible treatments included surgery, systemic therapy and RT (radiotherapy). Outcomes were evaluated as rates of disease-free survival (DFS) and of overall survival (OS). RESULTS: Forty-seven patients with CAM were included in the study. Metachronous CAM occurred 73 months (range 5-500 months) after diagnosis of the primary tumor. The median follow-up time was 5.4 years (interquartile range 2.9-7.0 years). The estimated OS was 72% at 5 years (95% CI 54-83), and 61% at 8 years (95% CI 43-75). The estimated DFS was 61% at 5 years (95% CI 44-74), and 42% at 8 years (95% CI 25-59). CONCLUSION: These findings, together with those from previous studies, show that CAM outcome, particularly if measured as OS, appear better than at other sites of distant dissemination, when CAM is subjected to surgical and systemic treatments with a curative intent. Therefore, a new clinical scenario is suggested where, in the TNM system, CAM is no longer classified as a stage IV, but as an N3 disease.

Modulatory effects of TGF-ß1 and BMP6 on thecal angiogenesis and steroidogenesis in the bovine ovary.

Angiogenesis plays an integral role in follicular and luteal development and is positively regulated by several intra-ovarian factors including vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 2 (FGF2). Various transforming growth factor-ß (TGF-ß) superfamily members function as intra-ovarian regulators of follicle and luteal function, but their potential roles in modulating ovarian angiogenesis have received little attention. In this study, we used a bovine theca interna culture model (exhibiting characteristics of luteinization) to examine the effects of TGF-ß1 and bone morphogenetic protein 6 (BMP6) on angiogenesis and steroidogenesis. VEGFA/FGF2 treatment promoted endothelial cell network formation but had little or no effect on progesterone and androstenedione secretion or expression of key steroidogenesis-related genes. TGF-ß1 suppressed basal and VEGFA/FGF2-induced endothelial cell network formation and progesterone secretion, effects that were reversed by an activin receptor-like kinase 5 (ALK5) inhibitor (SB-431542). The ALK5 inhibitor alone raised androstenedione secretion and expression of several transcripts including CYP17A1. BMP6 also suppressed endothelial cell network formation under VEGFA/FGF2-stimulated conditions and inhibited progesterone secretion and expression of several steroidogenesis-related genes under basal and VEGFA/FGF2-stimulated conditions. These effects were reversed by an ALK1/2 inhibitor (K02288). Moreover, the ALK1/2 inhibitor alone augmented endothelial network formation, progesterone secretion, androstenedione secretion and expression of several steroidogenesis-related genes. The results indicate dual suppressive actions of both TGF-ß1 and BMP6 on follicular angiogenesis and steroidogenesis. Further experiments are needed to unravel the complex interactions between TGF-ß superfamily signalling and other regulatory factors controlling ovarian angiogenesis and steroidogenesis.

Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology.

PURPOSE: This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. METHODS: The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. RESULTS: Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. CONCLUSIONS: A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.

Toxicity of Hydnora johannis Becca. dried roots and ethanol extract in rats.

AIM OF THE STUDY: Hydnora johannis Becca. (Hydnoraceae) commonly is used for the treatment of dysentery, diarrhoea, cholera and swelling tonsillitis in the folk medicine of Sudan and other African countries. This study evaluates the toxicological effects of Hydnora johannis roots on Wistar rats. MATERIALS AND METHODS: Rats were randomized into control, groups fed with 2, 10, 20% of dried roots for 8 weeks and other groups given ethanol extract (50, 100, 200 and 400mg/kg/day) through oral and intramuscularly administration for 2 weeks. Toxicity was evaluated using biochemical and histopathological assays. RESULTS: Alterations in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, cholesterol and urea were observed. Histopathological analysis revealed that the toxic effect were mainly on the liver, kidney and spleen on all treated groups. However, the impact of the dried roots was mild compared to the ethanol extract. Remarkably, there was a drop in cholesterol level in all treatment groups suggesting the antiartherogenic effect of Hydnora johannis roots. CONCLUSION: The results from this study suggest that the powder preparation as well as ethanolic extract of Hydnora johannis roots induced toxic effect on Wistar rats. The observed toxic effect might be due to the dose and/or frequency of administration. Although in traditional medicine the extract is administrated in low dose, the results suggest the necessity of standardization of the drug.

Hairy root induction of Papaver somniferum var. album, a difficult-to-transform plant, by A rhizogenes LBA 9402.

Two strains of Agrobacterium rhizogenes (15834, LBA 9402) and one Agrobacterium tumefaciens strain [GV 3101 (PMP90RK, p35SGUS-2)] and four culture media were tested and compared for their ability to induce hairy root formation on wounded Papaver somniferum L. hypocotyls. Five weeks after the infection with A. rhizogenes LBA 9402, hairy roots appeared on 80% of the hypocotyls maintained in the hormone-free liquid medium. Six hairy-root cultures were established. Transformation was confirmed by polymerase chain reaction analysis. One clone was analysed for its alkaloid production. The total alkaloid content was higher in the transformed roots (0.46+/-0.06% DW) than in the untransformed roots (0.32+/-0.05% DW). The transformed roots accumulated three times more codeine (0.18+/-0.02% DW) than intact roots (0.05+/-0% DW). Moreover, morphine (0.255+/-0.03% DW) and sanguinarine (0.014+/-0% DW) were found in the liquid culture medium.

Tropane alkaloid production by hairy roots of Atropa belladonna obtained after transformation with Agrobacterium rhizogenes 15834 and Agrobacterium tumefaciens containing rol A, B, C genes only.

Atropa belladonna leaf disks were infected by a wild strain Agrobacterium rhizogenes 15834 harboring the Ri-TL-DNA and by a disarmed Agrobacterium tumefaciens strain harboring a construction with only rol ABC and npt II genes. Thirteen root lines were established and examined for their growth rate and alkaloid productivity to evaluate the possible role of rol genes in morphological differentiation and in tropane alkaloid formation. A great diversity has been observed in the growth rate of these 13 root lines. The root biomass increased up to 75 times. The total alkaloid contents were similar in the root lines obtained by infection with A. rhizogenes 15834 and A. tumefaciens rol ABC. The last ones accumulated between 4 (1.1 mg g(-1) DW) and 27 (8 mg g(-1) DW) times more alkaloids than the intact roots (0.3 mg g(-1) DW). This work has shown that the rol ABC genes were sufficient to increase tropane alkaloid production in A. belladonna hairy root cultures.

Effects of the rol C gene on hairy root: induction development and tropane alkaloid production by Atropa belladonna.

Two series of Atropa belladonna hairy root lines were obtained, the first one transformed via Agrobacterium tumefaciens harboring rol C and npt II genes, and the other transformed with rol ABC and npt II genes. Thirteen hairy root lines were obtained and selected on hormone-free medium. The transformation was confirmed by PCR analysis, and these root lines were first examinated for their growth rate. Then hyoscyamine and scopolamine production was measured after 3 and 4 weeks of culture to evaluate the possible role of rol C gene in tropane alkaloid formation. The rol C gene alone played a significant role in the hairy root growth rate (17-fold increase). However this effect was much lower than that induced by the rol ABC genes together (75-fold increase). In contrast, the rol C gene alone was as efficient as the rol ABC genes together (mean value of total alkaloids: 0.36% dry weight, i.e., 12-fold times more than in untransformed roots) to stimulate the biosynthesis of tropane alkaloids in A. belladonna hairy root cultures.

Somatic embryogenesis and rhizogenesis of tissue cultures of two genotypes of Papaver somniferum: relationships to alkaloids production.

PAPAVER SOMNIFERUM L. tissue cultures, issued from various explants (cotyledons, hypocotyls, roots) derived from plantlets belonging to two genotypes, were established on LS solid medium containing growth regulators (NAA, Kin) in various combinations. Hypocotyls and roots were found to be interesting explants to obtain cellular development. Many roots developed on calli growing on a medium containing NAA (1 mg/l) + Kin (0.1 mg/l) for the PS genotype while somatic proembryos redifferentiated on calli issued from PS 1639 genotype. The same growth substance combination was the most favourable for the production of morphinan alkaloids and papaverine: up to 10 x 10 (-3)% DW in roots redifferentiated from PS calluses.

Porfiria cutánea tarda en dos pacientes con trasplante renal / Cutanea tarda porphyria in 2 patients with kidney transplantation

Two patients who developed porphyria cutanea tarda, six and eight years after a successful renal transplantation are reported. There was no history, in either of them, of alcohol abuse, blood transfusion, iron or estrogen therapy and any hemodialysis in the last years. There is no evidence to support that a renal allograft is capable to develop porphyria cutanea tarda. Nevertheless, it would be interesting to consider its possible influence, due to the longer survival of these patients.

Porfiria cutánea tarda en dos pacientes con trasplante renal / Cutanea tarda porphyria in 2 patients with kidney transplantation

Two patients who developed porphyria cutanea tarda, six and eight years after a successful renal transplantation are reported. There was no history, in either of them, of alcohol abuse, blood transfusion, iron or estrogen therapy and any hemodialysis in the last years. There is no evidence to support that a renal allograft is capable to develop porphyria cutanea tarda. Nevertheless, it would be interesting to consider its possible influence, due to the longer survival of these patients.(Au)

[Cutanea tarda porphyria in 2 patients with kidney transplantation]. / Porfiria cutánea tarda en dos pacientes con trasplante renal.

Two patients who developed porphyria cutanea tarda, six and eight years after a successful renal transplantation are reported. There was no history, in either of them, of alcohol abuse, blood transfusion, iron or estrogen therapy and any hemodialysis in the last years. There is no evidence to support that a renal allograft is capable to develop porphyria cutanea tarda. Nevertheless, it would be interesting to consider its possible influence, due to the longer survival of these patients.

Porfiria cutánea tarda en dos pacientes con trasplante renal. / [Cutanea tarda porphyria in 2 patients with kidney transplantation]

Two patients who developed porphyria cutanea tarda, six and eight years after a successful renal transplantation are reported. There was no history, in either of them, of alcohol abuse, blood transfusion, iron or estrogen therapy and any hemodialysis in the last years. There is no evidence to support that a renal allograft is capable to develop porphyria cutanea tarda. Nevertheless, it would be interesting to consider its possible influence, due to the longer survival of these patients.

Bacterial cavernous sinus aneurysm treated by detachable balloon technique.

We describe a patient who developed bilateral cavernous sinus septic thrombosis secondary to a suppurative lesion on the left cheek. Despite clinical improvement, left oculomotor symptoms recurred suddenly. A carotid artery aneurysm within the cavernous sinus was diagnosed by means of magnetic resonance imaging and confirmed by digital angiography. Follow-up angiograms showed an initial decrease in the aneurysm size, with subsequent enlargement. A latex contrast-filled balloon was successfully placed within the aneurysm, preserving the carotid parent artery blood flow. Our case illustrates the usefulness of the detachable balloon technique in the treatment of bacterial aneurysms of the cavernous sinus as an alternative treatment to carotid artery ligation.

Ferimentos perfurantes oculares com lesao cristaliniana: consideracoes sobre a conduta cirurgica inicial. / Perforating ocular injuries with crystallins injuries: considerations on the initial surgical procedure

Os autores realizaram um estudo retrospectivo envolvendo 52 pacientes com lesao cristalina entre 411 pacientes com FPO nos quais no ato cirurgico inicial nao se realizou remocao completa das massas. Destacam que apenas 3 deles (5,8%) apresentaram reabsorcao expontanea com acuidade visual final de 20/60 e 20/25. Concluem pela necessidade de remocao das massas quando houver seguranca no diagnostico de presenca delas em camara anterior bem como de vitrectomia anterior quando do envolvimento do segmento posterior