Cervical Lymph Node Metastases of Papillary Thyroid Carcinoma, in the Central and Lateral Compartments, in Children and Adolescents: Predictive Factors.

PROBLEM STATEMENT: The aim of our study was to identify predictive factors for lymph node metastases (LNM) in children and adolescents with papillary thyroid carcinoma (PTC) and their impact on survival. METHODS: The authors conducted an Italian multicentric retrospective analysis on 132 pediatric patients (0-18 years old) affected by PTC between 2000 and 2014. The investigated variables were demographic characteristics of the patients, clinicopathological features of PTCs, and persistence/recurrence of disease. The female/male ratio was 3.1:1. The median age was 14.3 ± 3.5 years (range 4-18 years). Total thyroidectomy was performed in all the patients, followed by lymph node dissection in 87 patients (65.9%). Metastatic lymph node involvement was confirmed in 73 patients (55.3%): lateral compartment (LC) in 25 patients (34.2%), central compartment (CC) in 17 patients (23.3%), and both compartments in 31 patients (42.5%). RESULTS: Multifocality (P < .00), vascular invasion (P = .04), infiltration of the thyroid capsule (P < .00), minimal extrathyroidal extension (P < .00), diffuse sclerosing variant of PTC (P = .02), and presence of LNM in the LC (P < .00) were significantly associated with LNM in CC. Infiltration of the thyroid capsule (P < .00), massive extrathyroidal extension (P = .03), distant metastases (P = .02), PTC, not otherwise specified (P < .00), and presence of LNM in the CC (P < .00) were significantly associated with LNM in LC. Age, sex and size of PTC were not correlated with the presence of cervical LNM. Moreover, presence of LNM in CC increases the risk of persistence (P < .01) and recurrence (P < .02) of PTC in children and adolescents. CONCLUSIONS: Most predictors, unfortunately, are only identified post-operatively by histopathologic examination: Just a small part of them can be pre-operatively detected with a low-sensitivity neck ultrasonography. In PTC patients with pre-operative predictors, we suggest an accurate pre- and intra-operative evaluation of CC and/or LC to find suspicious lymph nodes. The presence of LNM in CC has an impact on disease/progression/relapse-free survival. We suggest performing RAI therapy and an accurate follow-up for pediatric patients with only post-operative predictors.

Variation by stage in the effects of prediagnosis weight loss on mortality in a prospective cohort of esophageal cancer patients.

Cancer cachexia is increasingly recognized as a poor prognostic marker for various tumor types. Weight loss in esophageal cancer is multifactorial, as patients with bulky tumors also have reduced ability to eat. We aimed to investigate the relationship between prediagnosis weight loss and mortality in esophageal cancer and to determine whether these associations vary with tumor stage. We conducted a prospective cohort study of esophageal cancer patients at two tertiary centers. We recorded baseline patient characteristics including medications, smoking, body mass index, and weight loss in the year prior to diagnosis, and collected data on treatment and outcomes. We used Cox regression modeling to determine the associations between percent weight loss and outcomes. The main outcome of interest was all-cause mortality; secondary endpoints were esophageal cancer-specific mortality and development of metastases. We enrolled 134 subjects, the majority of whom had adenocarcinoma (82.1%); median percent weight loss was 4.7% (IQR: 0%-10.9%). Increasing percent weight loss was not associated with all-cause mortality (ptrend = 0.36). However, there was evidence of significant interaction by tumor stage (p = 0.02). There was a strong and significant association between prediagnosis weight loss and mortality in patients with T stages 1 or 2 (adjusted HR 8.26 for highest versus lowest tertile, 95%CI 1.11-61.5, ptrend = 0.03) but not for T stages 3 or 4 (ptrend = 0.32). Body mass index one year prior to diagnosis was not associated with mortality. Prediagnosis weight loss was associated with increased all-cause mortality only in patients with early stage esophageal cancer. This suggests that tumor-related cachexia can occur early in esophageal cancer and represents a poor prognostic marker.

Branchial cleft and pouch anomalies in childhood: a report of 50 surgical cases.

BACKGROUND AND AIMS: Branchial abnormalities occur when there is disturbance in the maturation of the branchial apparatus during fetal development. Branchial anomalies are congenital lesions usually present in childhood, even if they can be diagnosed later for enlargement or infection. A correct diagnosis will lead to proper management: complete surgical excision is the treatment of choice. The purpose of this article is to present clinical features, diagnostic methods and surgical treatment of branchial anomalies in childhood, based on a series of 50 patients. METHODS: We conducted a retrospective analysis of a total of 50 pediatric patients operated from June 2005 to June 2014 for the presence of branchial cleft anomalies. RESULTS: 27 cases (54 %) presented a second branchial cleft fistula and 11 cases (22 %) a second branchial cleft cyst and one case (2 %) presented both cyst and sinus of the second branchial cleft; four cases (8 %) presented first branchial cleft cyst whereas four cases (8 %) a first branchial cleft sinus and two cases (4 %) a first branchial cleft fistula; one case (2 %) presented a piriform sinus fistula (third branchial cleft). None of our patients presented anomalies of the fourth branchial cleft. All patients underwent surgical treatment and lesions have been removed by excision or fistulectomy. No post-surgical complication occurred. The rate of recurrence was 4 %. CONCLUSIONS: Pre-operative diagnosis supplies important information to the surgeon for a proper therapy: a complete excision of the lesion without inflammatory signs is essential to avoid re-intervention and to achieve a good outcome.

Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients.

PURPOSE: The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. METHODS: A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. RESULTS: The majority of patients (58.8 %) had tumors >2 cm in size. Nodal involvement occurred in 115/250 (46 %) patients and distant metastasis in 4 % (10/250). Total thyroidectomy and lobectomy were performed in 90.4 % (226/250) and 9.6 % (24/250) of patients, respectively. The overall rate of surgical complications was 20.8 % (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4 %, respectively), and vocal fold palsy (2.8 %). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12 % (30/250) with the vast majority of recurrences (96.6 %) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size > 2 cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100 %. CONCLUSION: Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.

Incidental ganglioneuromas: a presentation of 14 surgical cases and literature review.

BACKGROUND AND AIMS: Ganglioneuromas are benign tumors which originate from the neural crest. This tumor affects mainly young patients rather than adult ones, and its most frequent localizations are mediastinum, retroperitoneum, adrenal glands and cervical region. Usually, ganglioneuromas are discovered as incidentalomas since they are often asymptomatic, even if they could present sympathetic or mass-related symptoms. To obtain a definitive diagnosis, histological exam is necessary since CT scan and MRI are not capable of distinguishing ganglioneuromas from other tumors, such as neuroblastomas or pheocromocytomas. The surgical excision is the chosen treatment and it offers an excellent prognosis. METHODS: We conducted a retrospective analysis of our cases of ganglioneuroma from 2004 to 2014; this study aims to compare our experience with literature review (2000-2014). Data about patients' features, tumor localization, symptoms, treatment and follow-up were analyzed and reported in detailed tables. RESULTS: Between 2004 and 2014 we treated 14 patients affected by ganglioneuroma. For all of them the diagnosis was incidental; 9 out of 12 (64.3 %) patients presented an adrenal mass; in 2 patients (14.3 %) the tumor was localized in cervical region; in other 2 patients (14.3 %) the tumor was in the retroperitoneum and one patient (7.1 %) presented a ganglioneuroma in the costo-vertebral space. All our patients underwent surgical removal and none of them present surgery-related complications or recurrences to date. CONCLUSIONS: Our data widen the knowledge about ganglioneuroma and confirm that the surgical approach has an excellent prognosis with very low incidence of surgery-related complications and recurrences.

Minimally-invasive surgery in paediatric oncology: proposal of recommendations.

The Authors report a proposal of recommendations concerning Minimally Invasive Surgery (MIS) in Paediatric Oncology. Since the exact role of MIS in Paediatric Oncology is still not completely defined, a restrict panel of Italian Paediatric Surgeons, some interested in Oncologic Surgery, others in MIS, prepared a schematic document, mainly founded on literature data, to provide Paediatric Surgeons with recommendations useful to approach paediatric tumours with MIS. The final draft was approved by the Italian Group of Paediatric Oncologic Surgeons. The Authors summarize the feasibility of MIS, when performed with different purposes (biopsy / resection) and timing (initial / delayed surgery) for the most common solid tumours in children. The oncologic criteria must be always followed with MIS as well as with "open" surgery.

Functional ovarian lesions in children and adolescents: when to remove them.

STUDY OBJECTIVE: Functional ovarian lesions represent 45% of all pediatric adnexal abnormalities. Their surgical management, even if frequent, is not clear, especially in pediatric age. MATERIALS AND METHODS: We retrospectively reviewed 22 pediatric patients surgically treated for functional ovarian lesions from 2000 to 2006. The following characteristics were analysed: age, size of the lesion, ultrasound (US) aspect and clinical presentation. RESULTS: The average age was 16.1 years of age (range: 6 months-18 years). Of the 22 functional lesions, 12 (55%) were follicular cysts and 10 (45%) corpus luteum ones. The average size was 6.7 cm (range: 5.1-33 cm). US scan showed simple lesions in 10 cases (45%) and complex ones in 12 cases (55%). In 16 girls (72.8%) the presenting symptom was abdominal pain while 2 patients (9%) presented abdominal distention. In the other 4 patients (16.2%) the lesion was found accidentally during US examination. CONCLUSION: In pediatric subjects, functional ovarian cysts rarely required surgical intervention, though no complications or disorder recurrence were reported. To preserve ovarian function, conservative surgery has to be performed whenever feasible.

Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell-stimulating activities.

We have previously uncovered the impact of oncogenic and differentiation processes on extracellular vesicles (EVs) in cancer. This is of interested in the context of glioma stem cells (GSC) that are responsible for recurrent nature of glioblastoma multiforme (GBM), while retaining the potential to undergo differentiation and self renewal.  GSCs reside in vascular niches where they interact with endothelial cells through a number of mediators including bioactive cargo of EVs. GSCs can be classified as proneural (PN) or mesenchymal (MES) subtypes on the basis of their gene expression profiles and distinct biological characteristics. In the present study we investigated how GSC diversity and differentiation programmes influence their EV-mediated communication potentials. Indeed, molecular subtypes of GBMs and GSCs differ with respect to their expression of EV-related genes (vesiculome) and GSCs with PN or MES phenotypes produce EVs with markedly different characteristics, marker profiles, proteomes and endothelial stimulating activities. For example, while EVs of PN GSC are largely devoid of exosomal markers their counterparts from MES GSCs express ample CD9, CD63 and CD81 tetraspanins. In both GSC subtypes serum-induced differentiation results in profound, but distinct changes of cellular phenotypes including the enhanced EV production, reconfiguration of their proteomes and the related functional pathways. Notably, the EV uptake was a function of both subtype and differentiation state of donor cells. Thus, while, EVs produced by differentiated MES GSCs were internalized less efficiently than those from undifferentiated cells they exhibited an increased stimulatory potential for human brain endothelial cells. Such stimulating activity was also observed for EVs derived from differentiated PN GSCs, despite their even weaker uptake by endothelial cells. These findings suggest that the role of EVs as biological mediators and biomarkers in GBM may depend on the molecular subtype and functional state of donor cancer cells, including cancer stem cells. Abbreviations: CryoTEM: cryo-transmission electron microscopy; DIFF: differentiated GSCs; EGF: epidermal growth factor; DUC: differential ultracentrifugation; EV: extracellular vesicle; FGF: fibroblast growth factor; GBM: glioblastoma multiforme; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSC: glioma stem cells; HBEC-5i: human brain endothelial cells; MES: mesenchymal cells; MTS - [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; PMT1: proneural-to-mesenchyman transition cell line 1; PN: proneural cells; TEM: transmission electron microscopy; WB: western blotting.

Motor phenotype is not associated with vascular dysfunction in symptomatic Huntington's disease transgenic R6/2 (160 CAG) mice.

Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease. Vascular reactivity in different arterial districts was determined by wire myography in symptomatic R6/2 mice and age-matched wild type (WT) littermates. Disease stage was assessed by using well-validated behavioural tests like rotarod and horizontal ladder task. Surprisingly, no signs of vascular dysfunction were detectable in symptomatic mice and no link with motor phenotype was found.

[Update of the Italian Society of Nephrology Project No. 1 of the 2004-2006 SIN programme]. / Update sul progetto SIN n. 1 del programma SIN 2004-2006: qualità e accreditamento delle strutture di nefrologia, dialisi e trapianto.

In the last few years the Italian Society of Nephrology has addressed many technical-scientific and management aspects to better patient satisfaction. Project No. 1 of the 2004-2006 programme on 'Quality and Accreditation of National Renal Units' focuses on four essential points. The first is the questionnaire mailed to all the Presidents and Regional Delegates on the relationship between Nephrology units, Local Government Health-System and the Regional Healthcare Agency. The results evidence that the 'political' decision-making power of nephrologists decreases in the absence of a national strategy. The second point, in collaboration with the National Census Group, includes the quality analysis and the standardization of resources (human and structural) and management of the Renal Units. The third point is based on 'Educational Courses for Quality and Accreditation' held in Rome (3-5 October 2005: L'Accreditamento all'Eccellenza dell'Unita' Operativa di Nefrologia, Dialisi e Trapianto; 17-19 October 2005: Il Manuale di Accreditamento della Specialità di Nefrologia). The courses aim at training members responsible for each region to hold courses in their specific region to create a network including each single Renal Unit to create an acceptable homogenous language on the models of analysis and on the correct use of 'The Guide for Excellence Accreditation'. The fourth point concerns both the on-line Guide for Excellence Accreditation and 'Peer Review Accreditation' and the NEQUASY (Nephrology Quality System) project. The manual must be 'user friendly' allowing each Centre to self-evaluate using national and regional standards.

Completion total thyroidectomy in children with thyroid cancer secondary to the Chernobyl accident.

OBJECTIVE: To evaluate the usefulness of submitting children with thyroid cancer secondary to nuclear accidents to a completion total thyroidectomy. DESIGN: A case series consisting of patients living and operated on in Belarus whose parents had asked for a clinical evaluation in a western European center. SETTING: A tertiary care referral center. PATIENTS: The conditions of 47 children from Gomel, Belarus, with differentiated thyroid carcinoma following the nuclear accident at Chernobyl, Ukraine, were evaluated at the University of Pisa, Pisa, Italy. In approximately half of the cases, the treatment in Belarus consisted of a hemithyroidectomy. After a complete evaluation, the decision was made to reoperate on 19 of them by performing a completion total thyroidectomy. The preoperative evaluation revealed that 5 (26%) of the 19 patients who had undergone a hemithyroidectomy had unilateral recurrent nerve palsy and that 2 (10.5%) had hypoparathyroidism. INTERVENTIONS: Neck ultrasonography was used for the preoperative localization of thyroid residuals, thyroid nodules, suspicious lymph nodes, and a guided fine-needle aspiration biopsy specimen. The circulating thyroglobulin measurement was obtained before reoperation. An iodine 131 whole-body scan (WBS) was performed and circulating thyroglobulin levels were obtained after completion of the thyroidectomy during withdrawal of levothyroxine sodium therapy. MAIN OUTCOME MEASURE: The number of patients with a recurrence of thyroid cancer and lung or lymph node metastases after the completion total thyroidectomy. RESULTS: The results of the histologic examination were positive for papillary thyroid cancer in 6 (28.6%) of 21 patients, 3 with residual cancer in the remaining thyroid lobe and 3 with metastatic lymph node disease. A posttherapy WBS demonstrated lung metastases in 5 (28%) of 18 patients and lymph node metastases in 6 (33%) of 18 patients; the results of a posttherapy WBS were negative for metastases in 7 (39%) of 18 patients. Hypoparathyroidism developed in 4 (21%) of 19 patients who underwent a completion total thyroidectomy; unilateral laryngeal nerve palsy developed in 1 (5.2%) of these 19 patients. Among 22 children who previously underwent total thyroidectomy in Belarus, a diagnostic WBS showed lung metastases in 10 (45%) of the children and lymph node metastases alone in 3 (14%) of the children; the results of a diagnostic WBS were negative for metastases in 9 (41%) of the children. Statistical analysis showed a nonsignificant (P>.05) difference in the prevalence of lung and lymph node metastases in patients who previously underwent total thyroidectomy compared with patients who underwent completion total thyroidectomy. CONCLUSION: Completion total thyroidectomy allowed for the diagnosis and treatment of recurrent thyroid cancer and lung or lymph node metastases in 61% (11/18) of the patients in whom residual differentiated thyroid carcinoma was not previously recognized.

Combined renal and pyelic fusion with crossed ectopia of single ureter.

A case of a forty-five-year-old woman with fused kidneys and intercommunicating pelves drained by a single ureter crossing the midline is reported. A review of the literature is presented.

Multicentric breast tumour: an anatomical-clinical study of 100 cases.

Multicentric tumours (MT) represent a potential limit to the treatment by conservative surgery of cancer of the breast. In order to determine which anatomical-clinical features of breast cancer would indicate the highest risk of MT, we studied 100 patients with MT and 452 patients with unicentric tumours (UT), all of whom had been subjected to radical mastectomy during the period 1980 to 1988. Statistical analysis showed a significant difference between the two groups of parameters for bilateral breast cancer (with regard both to metachronous and synchronous lesions), for primary tumours of over 2 cm in size, for both lobular and invasive ductal histotypes and for involvement of the nipple-areola complex. Therefore, if the indications in favour of conservative surgery are applied accurately in combination with radiation therapy, the clinical and biological significance of multicentricity is minimized.

Carotid body tumours. A review of eight cases.

Between 1968 and 1988, eight patients with carotid body tumour have been operated on at Istituto di Clinica Chirurgica at the University of Pisa. We undertook the follow-up of all these patients. Two of them presented with bilateral and familial lesions. There was no mortality or morbidity, except in one patient, who had the vagus resected because it was invaded by tumour. For investigation of familial occurrence we have found ultrasound very useful for screening.

Symptomatic adrenal myelolipoma: therapeutic considerations.

Four cases of symptomatic myelolipoma of the adrenal gland are presented. Three were treated at laparotomy and one with a laparoscopic approach. On the basis of these four cases we discuss the aetiology, pathogenesis, clinical manifestations, diagnosis and treatment of this rare disease. We also report the follow-up of a patient with bilateral myelolipoma, who underwent monolateral excision. We conclude that myelolipoma, if correctly diagnosed, can be treated conservatively with careful follow-up, limiting surgery to symptomatic cases.

Correlation between 5-year survival of T1-T2N0 breast cancer and some pathological parameters.

In order to more clearly define the factors influencing prognosis, 113 cases of T1-T2N0 breast cancers, all operated on by means of radical mastectomy, were reviewed. The following pathologic parameters were analyzed in relation to 5 years survival: histological type, nuclear grading, vascular embolization, size and border of the tumour, and sinus histiocytosis, diffuse cortical hyperplasia and germinal center hyperplasia of axillary nodes. We observed a close correlation between the presence of sinus histiocytosis and prognosis, as many authors have reported. Diffuse cortical hyperplasia stands out from our data as the most unfavourable prognostic factor.

Vascular endothelial growth factor (VEGF) and other common tissue prognostic indicators in breast cancer: a case-control study.

VEGF is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathological conditions. Nevertheless, VEGF tissue evaluation in cancer patients as a prognostic factor compared to the conventional histological and biological parameters is still controversial. In this case-control study, tissue VEGF was retrospectively determined by immunohistochemistry and related to T, N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 in 129 breast cancer patients. Seventy-four of these patients had developed distant metastases postoperatively. The remaining 55 patients had remained disease-free >10 years after surgery. In 17 (13%) of the 129 patients (six with distant metastases and eleven disease-free) tissue and plasma VEGF were concomitantly evaluated. In univariate analysis no significant differences in VEGF and tumor size were found between metastatic and disease-free patients, whereas there were significant differences in N, ER, PgR, c-erbB-2, p53, MIB-1 and cyclin D1 (p ranging from 0.001 to 0.0001). In multivariate analysis VEGF showed less significance than N, ER, c-erbB-2, MIB-1 and cyclin D1 (p = 0.012, p = 0.007, p = 0.005, p = 0.005, p = 0.002 and p = 0.001, respectively). VEGF was a significant unfavorable prognostic indicator only in the N+ subset (p = 0.015), while ER (p = 0.05 and p = 0.021) and MIB-1 (p = 0.031 and p = 0.022) were significant in both the N+ and N- subgroups. In multivariate analysis in the 74 metastatic cases VEGF did not show any significance in relation to disease-free interval and overall survival from the time of mastectomy and from the time of relapse, whereas N and PgR did (p ranging from 0.018 to 0.001). In conclusion, tissue VEGF does not seem a suitable candidate to replace conventional histological and other common biological prognostic factors in breast cancer.

Long-term monitoring of cell-mediated immunity in disease-free breast cancer patients: a preliminary retrospective study.

In 102 N- and 44 N+ disease-free breast cancer patients, lymphocytic populations and skin reaction of delayed hypersensitivity (SRDH) were monitored up to 266 months after mastectomy to find out whether they were similar or different from control values. In two selected groups of 34 N- and 11 N+ breast cancer patients, the whole 10 year follow-up was divided into three subintervals, each of them lasting 40 months and the time course of lymphocytic populations was evaluated. In the 102 N- patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.01, P < 0.001, P < 0.01, respectively) while CD4+/CD8+ ratio was higher (P < 0.05) than in controls. Fifteen N- breast cancer patients (16%) were anergic compared to 30(32%) of controls (P < 0.05). In the 34 selected N- breast cancer patients soon after mastectomy the mean value of CD4+, CD8+, CD3+ T subpopulations was lower (P < 0.01, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value increased so that in the last subinterval they were not or were only slightly lower (P n.s., P < 0.05, P < 0.05, respectively) than in controls. In the 44 N+ patients, mean CD4+, CD8+, CD3+ values were lower (P < 0.001, v < 0.05, P < 0.01, respectively) and CD19+ lymphocytes higher (P < 0.001) than in controls. Five N+ breast cancer patients (13%) were anergic compared to 32% of controls (P < 0.05). In the 11 selected N+ breast cancer patients soon after mastectomy, the mean value of CD4+, CD8+ T subpopulations and CD16+56+ cells was significantly lower (P < 0.001, P < 0.001, P < 0.01, respectively) than in controls. Successively their mean value constantly increased so that in the last subinterval, no or slight (P n.s., P < 0.05, P n.s., respectively) significant difference compared to controls occurred. The mean CD4+/CD8+ ratio value of N- patients was significantly higher than in controls. However in the last subinterval, the significance was lower than in the first one (P < 0.05 and P < 0.01, respectively). In the N+ patients, the mean value of CD4+/CD8+ ratio was constant, although not significantly, lower than in controls; however it progressively increased from the first to the last subinterval. Therefore the significance of the difference of the mean CD4+/CD8+ ratio between N- and N+ patients strongly decreased from the first to the last subinterval (P < 0.001 and P < 0.05, respectively). These data indicate that in breast cancer patients, following mastectomy, a significant activation of memory and CD4+ T cells and long-term decrease of the circulating immunocompetent CD4+, CD8+ and CD16+56+ cells occurs. The prolonged disease-free interval observed in the 34 N- and 11 N+ breast cancer patients can be correlated with the restoration of the normal state of cell-mediated immunity.

Filgrastim and lack of support of intensive adjuvant chemotherapy for high-risk breast cancer patients.

The capacity of filgrastim to reduce the myelotoxicity of a 16-week intensive chemotherapy regimen has been investigated in 24 operable breast cancer patients with > or = 10 metastatic axillary nodes. Five patients were treated with chemotherapy alone (control group); 19 patients were treated with chemotherapy and filgrastim, 5 microg/kg/day s.c. Six patients in the latter group were treated from day 4 to day 7 (level 1), seven from day 10 to day 13 (level 2), and six from day 4 to day 7 and day 10 to day 13 (level 3). A total of 135 courses were administered: neutropenia was the most severe toxicity, and the prophylactic use of filgrastim does not reduce its severity. Moreover, the dose intensities of antiblastic drugs actually received by the patients were not significantly different in the four study groups. Among the patients treated at level 3, there were three toxic deaths: one patient died because of febrile neutropenia and sepsis, two patients because of ischemic colitis. At a median follow-up of 15 months, 17 patients were alive, and 15 patients were disease free. The use of filgrastim does not ameliorate myelotoxicity and does not allow the administration of the planned doses of antiblastic drugs of a 16-week intensive chemotherapy regimen.

Central precocious puberty in 48,XXYY Klinefelter syndrome variant.

We report the first case of central precocious puberty in a patient with 48,XXYY Klinefelter syndrome variant. We also report clinical characteristics, growth pattern, endocrine data and pathological testicular findings. The patient did not receive medical care for his precocious pubertal development, because of adequate height prognosis, and reached normal height for both his target height and Klinefelter patients. Since precocious puberty seems to occur in Klinefelter syndrome and its variants, we advise karyotype analysis in boys with mental retardation, gynecomastia, small testes and precocious onset of puberty.