Prevention of diffuse, minimal lymphatic "retention" with Robuvit®: a concept, supplement registry study.

BACKGROUND: The aim of this study was to evaluate the effects of the standardized supplement Robuvit® (oak wood extract) in defined diffuse, minimal lymphatic "retention" (DMLR). METHODS: Robuvit® has already been investigated in both primary and secondary (post-surgical, post chemo-radiotherapy) lymphatic insufficiency. This registry included subjects with diffuse, minimal lymphatic "retention" (DMLR). The registry management groups included women with mild-moderate limb swelling using standard management (SM) as controls. A second, comparable group used prevention with Robuvit® at the dosage of 3 cp/day (300 mg/day) for 4 weeks. RESULTS: No tolerability problems or side effects were observed with the preventive supplementation. The management groups (34 women in total), including 18 women in Robuvit® and 16 in SM were comparable in age and baseline evaluations. After 4 weeks, in the Robuvit® group, edema scale values derived from ultrasound observations decreased significantly (P<0.05) at all measurement's sites, from the proximal (inguinal) level to the more distal (ankle-foot) level. No significant changes in edema were observed in control subjects. Generally, in areas with higher level of edema (distal areas at the foot and ankle), the edema decrease was larger than in more proximal, ultrasound measurement sites. CONCLUSIONS: Preventive Robuvit® supplementation appears to be safe and effective in controlling DMLR in subjects without significant or apparent clinical conditions. This preventive, concept study should be extended to a larger population for more meaningful observations.

High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice.

Vitamin C (VC) is an essential nutrient for humans and certain other animals. It has antioxidant properties and has been reported to ameliorate oxidative damage to lipids, DNA and proteins. However, the effects of VC on immune function are poorly understood, especially the influence of long-term high-dose VC intake on the number and function of immune cells. In the present study, to evaluate the immune effects of VC, VC-deficient senescence marker protein-30 knockout (SMP30KO) mice were fed a diet containing the recommended level of VC (20 mg/kg per d; 0·02 % VC) or a high level of VC (200 mg/kg per d; 0·2 % VC) for 1 year. The plasma VC concentration of the 0·02 % group was the same as that of age-matched C57BL/6 mice after 1 year of feeding; however, plasma VC concentration and thymus weight were significantly higher in the 0·2 % VC group than in the 0·02 % VC group. The total counts of leucocytes, lymphocytes, granulocytes and monocytes in the peripheral blood, as well as the number of splenocytes and thymocytes, were all significantly higher in the 0·2 % VC group than in the 0·02 % VC group. In addition, the number of naive T cells in peripheral blood lymphocytes, the number of memory T-cell populations in splenocytes, and the number of cluster of differentiation (CD)4⁺CD8⁺ or CD4⁺CD8⁻ or CD4⁻CD8⁺ T cells in thymocytes were all markedly higher in the 0·2 % VC group than in the 0·02 % VC group after 1 year of dietary treatment. These results suggest that a long-term high-dose intake of VC is effective in the maintenance of immune cells, partly through the suppression of age-related thymic involution in VC-deficient SMP30KO mice.

Occult primary breast cancer at a comprehensive cancer center.

BACKGROUND: Management of occult primary breast cancer (OPBC), that is, breast cancer that first presents through regional nodal or distant disease without clinical or mammographic evidence of disease in the breast, has been controversial and inconsistent. Here, we review OPBC patients treated at our institution. METHODS: We conducted a retrospective review of women diagnosed with a first primary breast cancer between March 1999 and September 2010 to identify patients who presented with isolated axillary lymphadenopathy proven to be histologically consistent with primary breast malignancy but had no evidence of a breast mass on physical examination, mammography, or ultrasound. Descriptions of treatments received, recurrence, morbidity, and mortality as of October 2012 are reported. RESULTS: Of 5533 patients reviewed, seven (0.1%) patients were identified. The median age was 65 y old (range, 40-72), and the median length of follow-up was 86 mo (range, 42-124). Four patients underwent modified radical mastectomy, one patient had a lumpectomy and axillary lymph node dissection, and two patients had axillary lymph node dissection without breast surgery. Four patients received adjuvant radiation therapy. All seven patients received chemotherapy. Three patients received endocrine therapy, and two patients received anti-HER2 therapy. At the last follow-up, all seven patients were alive with no evidence of disease. CONCLUSIONS: Although there was some variation in the management of OPBC at our institution, our patients had excellent outcomes after multimodal treatment. Our results support a curative intent approach to the treatment of OPBC and illustrate the need for individualized treatment algorithms based on tumor biology and extent of the disease at diagnosis.

Experimental infection of a newly emerging Korean type I porcine reproductive and respiratory syndrome virus isolate in colostrum-deprived pigs.

BACKGROUND: Recently, new emergence of type I PRRSV has been reported in Korea by several research groups. Although specific subgroups of type I PRRSVs in Korea were observed in the previous phylogenetic analysis, there is a lack of information about the virulence of type I PRRSV recently isolated in Korea. METHODS: One type I PRRSV isolate (G2446, 3 times passaged in primarily cultured pulmonary macrophages) in Korea was experimentally infected in colostrum-deprived pigs. The pathological and serological evaluations were performed and compared to type II PRRSV strain (CP07-401-9, 5 times passaged in MARC-145 cell lines)-infected pigs, for 21 days post challenge (dpc). RESULTS: The pneumonia found in gross examination was more severe in type I PRRSV-infected pigs than type II PRRSV-infected pigs. Both groups showed bronchointerstitial pneumonia, mild multifocal perivascular lymphohistiocytic myocarditis and lymphadenopathy at 14 dpc. However, the unique histopathologic lesions were not found in the pigs experimentally infected with a Korean type I PRRSV isolate, when compared to previous data about classical pathology of PRRSV. The PRRS-specific antibodies were detected in the first week after challenge and viremia continued at least until 21 dpc in both groups. CONCLUSION: The gross and histopathologic lesion in this study indicated that Korean type I PRRSV strain (G2446) caused classical PRRSV-specific lesions. Although this study evaluated one representative strain of Korean type I PRRSV, the results may provide information regarding the pathogenicity of type I PRRSV recently emerged in Korea.

Cervical lymphadenopathies signaling thyroid microcarcinoma. Case study and review of the literature.

BACKGROUND: Some lateral cervical lymphadenopathies may lead to the discovery of papillary microcarcinomas (PMC) of the thyroid that are not radiologically apparent. This relatively rare clinical situation raises questions about the diagnostic approach to chronic cervical lymphadenopathy and the impact of lymph node metastasis on PMC prognosis. PURPOSE OF THE ARTICLE: To study the epidemiologic, clinical, and prognostic criteria of cases of lymphadenopathy that signaled PMC. PATIENTS AND METHODS: A retrospective study of 167 consecutive cases of PMC compared with 13 cases where a cervical mass signaled other forms of PMC. RESULTS: The mean age was 48.5 years, the ratio of men to women was 5:8, and the mean PMC size was 5.5mm. These data did not differently significantly from those of the other PMC cases. The preoperative imaging found fluid content in six cases, with microcalcifications in three cases. All cases were treated by modified radical neck dissection on the side with the lymphadenopathy and total thyroidectomy with central neck dissection. The lymphadenopathy included a ruptured capsule in five cases and was accompanied by central lymph node metastases in three cases. Thyroid capsule involvement was significantly more common in cases of PMC discovered due to lymphadenopathy than in other cases of PMC (69% versus 9.7%, respectively; p<0.001). The mean follow-up was 7.3 years. There were no deaths due to PMC signaled by lymphadenopathy. Two cases of lymph node recurrence after 8 and 10 years were controlled by another surgery and radioactive iodine treatment. CONCLUSION: Any chronic cervical mass should suggest the possibility of thyroid origin, especially in cases with cystic content or microcalcifications in subjects with no particular risk factors. An ultrasound of the thyroid should be done, as well as a fine needle aspiration biopsy of the lymphadenopathy with a thyroglobulin assay. Treatment is the same as for any thyroid carcinoma, and results in a good oncological outcome, despite the possibility of lymph node recurrences.

Association between lymph node silicosis and lung silicosis in 4,384 German uranium miners with lung cancer.

This study investigates the association between lymph node-only and lung silicosis in uranium miners with lung cancer and exposure to quartz dust. Tissue slides of 4,384 German uranium miners with lung cancer were retrieved from an autopsy archive and reviewed by 3 pathologists regarding silicosis in the lungs and lymph nodes. Cumulative exposure to quartz dust was assessed with a quantitative job-exposure matrix. The occurrence of silicosis by site was investigated with regression models for exposure to quartz dust. Miners with lung silicosis had highest cumulative quartz exposure, followed by lymph node-only silicosis and no silicosis. At a cumulative quartz exposure of 40 mg/m(3) × years, the probability of lung silicosis was above 90% and the likelihood of lymph node-only silicosis and no silicosis do not differ anymore. The results support that lymph node silicosis can precede lung silicosis, at least in a proportion of subjects developing silicosis, and that lung silicosis strongly depends on the cumulative quartz dose.

Survey of orbital tumors at a comprehensive cancer center in the United States.

BACKGROUND: The purpose of this study was to evaluate the frequencies of various types of orbital lesions seen at a comprehensive cancer center in the United States. METHODS: In this retrospective case series, we reviewed the medical records of 268 consecutive patients referred to our orbital oncology service for evaluation of an orbital mass between November 1998 and February 2009. Each orbital lesion was documented by CT and/or MRI, and in most cases diagnosis was established with a tissue biopsy. Patients who were seen for second opinions and had inadequate follow-up data were excluded, as were patients with thyroid eye disease or orbital hemorrhage. RESULTS: The study included 134 men and 134 women aged 1 to 89 years at diagnosis (median, 55 years). Follow-up ranged from 0.06 to 192 months (median, 15 months). Of the tumors, 171 (64%) were primary orbital, 69 (26%) were secondary orbital, and 28 (10%) were metastatic tumors. Lesion types were as follows: secondary orbital tumors, 69 (26%); lymphoproliferative lesions, 68 (25%); metastases, 28 (10%); epithelial lacrimal gland tumors, 27 (10%); inflammatory conditions, 21 (8%); vascular lesions, 20 (7%); mesenchymal tumors, 18 (7%); optic nerve and nerve sheath tumors, 7 (3%); peripheral nerve tumors, 3 (1%); histiocytic lesions, 3 (1%); cystic lesions, 3 (1%); and other lesions, 1 (<1%). The most common histopathologic diagnoses were lymphoma, 50 cases (19%); orbital extension of sinus tumor, 25 (9%); lacrimal gland adenoid cystic carcinoma, 18 (7%); cavernous hemangioma, 15 (6%); orbital extension of brain tumor, 14 (5%); idiopathic orbital inflammation, 14 (5%); plasmacytoma, 8 (3%); reactive lymphoid hyperplasia, 7 (3%); metastatic breast cancer, 7 (3%); orbital extension of ocular adnexal basal cell carcinoma, 7 (3%); orbital extension of ocular adnexal melanoma, 6 (2%), rhabdomyosarcoma, 6 (2%); metastatic gastrointestinal cancer, 5 (2%); sarcoidosis, 5 (2%); and other less common lesions. Forty-two lesions (16%) were intraconal, and 226 (84%) were extraconal. There were 169 (63%) malignant tumors and 99 (37%) were benign tumors. The rate of malignant lesions was 65% in children and 63% in adults (≥18 years). Malignant conditions encountered at a higher rate than previously reported included lymphoma (19% vs 8% to 13%), secondary orbital tumors (26% vs 13% to 20%), orbital metastases (10% vs 2% to 7%), and malignant epithelial lacrimal gland tumors (9% vs 2% to 3%). CONCLUSION: Our findings highlight the distinctive nature of the orbital oncology experience at a comprehensive cancer center. We found higher than previously reported rates of malignant tumors (63% of all tumors), particularly secondary tumors, malignant epithelial lacrimal gland tumors, and orbital metastases.

Ulinastatin alone does not reduce caspase 3-mediated apoptosis in protease-positive Aeromonas hydrophilia-induced sepsis.

BACKGROUND/PURPOSE: To evaluate the effect of ulinastatin, a protease inhibitor, on survival and apoptosis in protease-positive Aeromonas hydrophilia (PPAH)-induced sepsis. METHODS: Thirty mice were randomly allocated to receive intraperitoneal injection of either phosphate buffered saline (PBS) (control mice, n = 10) or PPAH (PPAH mice, n = 20). After 30 minutes, control mice received an additional intraperitoneal PBS injection, 10 PPAH mice received intraperitoneal PBS injection (non-treated PPAH mice), and the remaining 10 PPAH mice received an intraperitoneal injection of ulinastatin (ulinastatin-treated PPAH mice). RESULTS: Survival at 24 hours was 100% in control mice, and 35% (p < 0.05) in PPAH mice; the survival rate in non-treated and ulinastatin-treated PPAH mice were 30% and 40% (p > 0.05), respectively. The thymus weight (mg) decreased significantly in PPAH mice (51.1 +/- 14.9) compared to control mice (69.7 +/- 14.4; p < 0.001); there was no difference between ulinastatin-treated (52 +/- 13.9; p > 0.05) and non-treated PPAH mice (50.4 +/- 16). The thymus gland cell count reduced significantly in PPAH mice (8.1 +/- 4.7 x 10(7)) compared to control mice (12.8 +/- 6.6 x 10(7); p < 0.01), and immunofluorescence analysis demonstrated that the reduced cells were mostly CD4+ CD8+, in contrast to the increase in CD4+ CD8- cells. There was no difference in cell count between ulinastatin-treated (8.7 +/- 4.9 x 10(7)) and non-treated PPAH mice (7.4 +/- 4.6 x 10(7); p > 0.05). Caspase 3-mediated apoptosis was not detectable in control mice in contrast to the pronounced manifestation in PPAH mice. CONCLUSION: PPAH-induced sepsis has a high mortality that is related to lymphocyte apoptosis. Ulinastatin alone does not significantly reduce caspase 3-mediated lymphocyte apoptosis.

Disseminated pagetoid reticulosis (Ketron-Goodman disease): six-year follow-up.

Pagetoid reticulosis consists of 2 types: Woringer-Kolopp and Ketron-Goodman disease (K-G). Compared with the former, K-G may have disseminated lesions and a guarded prognosis. We encountered a case of K-G in a 67-year-old man with disseminated plaques on the neck, the trunk, and both extremities. Histologic specimens demonstrated medium- to large-sized, atypical cells infiltrating in the lower epidermis. The phenotype (CD3(+), CD4(-), CD8(-), CD45RO(-), CD45RA(+)) and ultrastructural findings suggest that these cells were immature T cells. Although PUVA was initially effective, new plaques in which atypical cells are still present histologically, have appeared through a 6-year follow-up. Literature review revealed the high rate of recurrence. These findings suggest that K-G is an epidermotropic or immature T-cell variant of mycosis fungoides. In patients with K-G, therefore, long-term observation is necessary: Disappearance of cutaneous lesions may not mean cure.

Adenopatías cervicales en Oncología. Clínica, diagnóstico y tratamiento / Cervical adenopathies in Oncology. Clinical presentation, diagnosis and treatment

Las adenopatías cervicales representan el síntoma de aparición del 12 por ciento de los tumores de cabeza y cuello. Ante una tumoración cervical se ha de establecer el diagnóstico diferencial entre tres etiologías: congénita, infecciosa y neoplásica. El diagnóstico de sospecha se debe confirmar mediante la realización de una punción aspiración con aguja fina (PAAF), que nos proporcionará el diagnóstico histológico en más del noventa por ciento de los casos. La correspondencia entre la localización de la adenopatía y sus territorios de drenaje linfático indica la localización probable del tumor primario. La localización del tumor primario, la estadificación, la histología, el grado de aneuploidía y el estado inmunológico del enfermo se han citado como factores que predisponen al tumor primario a metastatizar. La metástasis de origen desconocido constituyen el 5 por ciento de las adenopatías metastásicas, y su diagnóstico precisará la realización de biopsias aleatorias en las regiones donde las neoplasias de localización submucosa metastatizan de forma temprana. La localización, la histología, la estadificación y la aparición del tumor primario se han citado como factores pronósticos en esta entidad (AU)

Massive macrophage lipid accumulation presenting as hepatosplenomegaly and lymphadenopathy associated with long-term total parenteral nutrition therapy for short bowel syndrome.

We present a unique case of massive splenomegaly, hepatomegaly, and lymphadenopathy caused by lipid-laden macrophages in a 50 year old white female with short-bowel syndrome treated with long-term total parenteral nutrition. Using transmission electron microscopy and special stains we were able to show that the total parenteral nutrition lipid component was composed of lipid droplets and micelles morphologically identical to those found in lipid-laden macrophages which had accumulated in the patient's reticuloendothelial system leading to massive splenomegaly, hepatomegaly (without evidence of steatosis) and lymphadenopathy. While this phenomenon has been reported in animal models, no human cases have been previously reported.

[The biochemical and morphological changes in the body in experimental thymomegaly and their correction with sodium selenite]. / Nekotorye biokhimicheskie i morfologicheskie izmeneniia v organizme pri éksperimental'noi timomegalii i ikh korrektsiia selenitom natriia.

A model of thymomegaly in puppies was used for a study of changes in the content of nucleic acids, protein, glycogen, ATP, cuprum, manganese, iron, zinc, succinate dehydrogenase and cytochromoxidase activity in tissues of the thymus, spleen, adrenal glands, liver and associated morphological changes in tissues of these organs, lymph nodes and the thyroid. In animals receiving sodium selenite normalization of the above indices was more marked than in untreated animals.

Silicone lymphadenopathy associated with augmentation mammaplasty. Morphologic features of nine cases.

Silicone lymphadenopathy (SL)--defined as the presence of silicone in a lymph node--is a rare side effect of mammary augmentation either by injection of liquid silicone or by placement of a bag-gel prosthesis. Nine new cases in eight patients are herein reported and compared with six previously well-documented cases. The available data showed that SL was frequently detected as an incidental finding of no clinical significance during mastectomy and nodal dissection for associated breast carcinoma (nine cases), but may present as a painful or nontender enlarged lymph node (six cases). The latter presentation was almost always associated with a history of injection of liquid silicone or rupture of the prosthesis. All or some of the following findings were present in an affected lymph node: coarse vacuoles, fine vacuoles, and multinucleated giant cells. All lymph nodes contained a variable amount of an unstained, nonbirefringent, refractile material that, in seven of our cases, was shown to contain elemental silicon by energy-dispersive x-ray elemental analysis. In 312 lymph nodes collected from 18 routine cases of breast carcinoma, coarse vacuoles probably representing fat were found in 107 lymph nodes (34%); focal fine vacuoles were found in one (0.3%), and a single multinucleated giant cell was found in one (0.3%). In conclusion, SL probably will be encountered more frequently when cancer-prone age is reached by the susceptible population. In most cases, it is an incidental finding of no clinical significance. However, the histologic diagnosis can be made by observing characteristic light-microscopic changes, which may be supplemented in doubtful cases by energy-dispersive x-ray analysis.

Successful treatment of autoimmunity in MRL/1 mice with LS-2616, a new immunomodulator.

Autoimmune MRL/1 mice were treated with a recently developed substance with immunomodulating properties, LS-2616. Treatment was initiated at the age of 8 weeks, before the onset of clinically apparent disease, and at 16 weeks of age, after development of established lupus disease. Beneficial therapeutic effects were obtained, even when LS-2616 was administered at the lowest dose tested (1 mg/mouse/week) to 16-week-old mice. The effects of LS-2616 on longevity, as well as on development of lymphadenopathy, splenomegaly, glomerulonephritis, and vasculitis, were pronounced and were comparable with those of cyclophosphamide. The results obtained suggest a potential role for LS-2616 in the treatment of autoimmune disease in humans.

[Paraneoplastic multicentric reticulohistiocytosis: induced and inductable by iodine containing x-ray contrast media]. / Paraneoplastische multizentrische Retikulohistiozytose: Durch jodhaltige Röntgen-Kontrastmittel ausgelöst und provozierbar.

Following lymphography, a 41-year-old woman developed arthritis and papules of multicentric reticulohistiocytosis three years after the beginning of a carcinoma of the cervix, now inoperable and with vulvar metastases. Two further inevitable x-ray investigations with different contrast media led to exacerbation of the disease within 24 hours. 12 month after onset, all symptoms of multicentric reticulohistiocytosis receded spontaneously, and further investigations with contrast media were well tolerated. We assume that iodine compounds may be the cause--directly or indirectly--for provocation and enhancement of histiocytic proliferation.

Malignant histiocytosis resistant to anthracycline. Response to intensive treatment with etoposide and amsacrine.

A 36-year-old woman, presenting with fever, pancytopenia, hepatosplenomegaly, and striking effacement of the bone marrow by true malignant histiocytes, was found to have no benefit from the systemic administration of cyclophosphamide, vincristine sulfate, doxorubicin, prednisone, and high-dose methotrexate with calcium leucovorin rescue. Striking histologic and clinical improvement was noted after the administration of two cycles of etoposide and amsacrine, each cycle consisting of 100 mg/sq m/day of each agent for five days. We believe that this therapy should be considered for future patients demonstrating aggressive presentations of malignant histiocytosis.

The spectrum of mastocytosis.

Mastocytosis represents a spectrum of clinical disorders that results from an aberrant proliferation of tissue mast cells. This disease process may be confined to the skin (cutaneous mastocytosis) or may involve multiple organs (systemic mastocytosis). Parameters that are useful in differentiating cutaneous from systemic disorders include patient age, symptom complex, and clinical signs. A wide range of clinical symptoms may be encountered in patients with mastocytosis which result from the release of pharmacologically potent mast cell mediators. Distinct cutaneous patterns resulting from skin mast cell infiltrates can be helpful in identifying patients with systemic involvement. The diagnosis of mastocytosis is confirmed by demonstrating increased tissue mast cells in involved organs. The overall prognosis for patients with proliferative mast cell disease is relatively good, although a small percentage are at risk for developing a fatal neoplastic disorder (malignant mastocytosis). Treatment of mastocytosis is directed at both inhibiting mast cell degranulation and blocking the potential systemic effects of released secretory products. Future therapeutic advances depend upon an improved understanding of the basic mechanisms involved in mast cell mediator release and the forces that govern mast cell growth and development.