Simple enucleation for the treatment of renal angiomyolipoma

OBJECTIVES: To report on the role of simple enucleation for treating renal angiomyolipoma (AML) in a series of patients treated in our department. PATIENTS AND METHODS: We retrospectively reviewed the data of all 37 patients with a histopathological diagnosis of renal AML who had either radical nephrectomy (three) or nephron-sparing surgery by simple enucleation (34) between January 1986 and December 2005. Indications for intervention included either symptomatic AML or a tumour of >4 cm, regardless to the presence of symptoms or renal masses suspicious of malignancy. The patients' status was evaluated last in October 2006. RESULTS: The mean (sd, median, range) pathological tumour size was 5.2 (3.4, 4.8, 1.5-15) cm; five patients (15%) were affected by tuberous sclerosis. Simple enucleation was successful in all patients but in three (9%) a sharp dissection a few millimetres from the tumour was used during critical steps of the procedure where it seemed difficult to define the right plane of enucleation. Warm ischaemia was used in 79% of patients, with a mean ischaemic time of 11.2 min. Two patients (6%) required renal hypothermia. A simple parenchymal compression was used in five cases (15%). The mean (range) intraoperative blood loss was 170 (70-650) mL. None of the patients had postoperative bleeding requiring re-intervention but one (3%) required two units of blood after surgery. There were no major complications, e.g. prolonged acute tubular necrosis/chronic renal insufficiency and urinary leakage/urinoma, but two patients had urosepsis not associated with perirenal fluid collection and that required targeted antibiotic therapy. At a mean (median, range) follow-up of 56 (50.5, 10-120) months none of the patients had local tumour recurrence. Two patients had a small AML elsewhere in the operated kidney, detected 18 and 36 months after surgery, with a kidney recurrence rate of 6%. CONCLUSIONS: Our data confirm the optimum results of simple enucleation for renal AMLs; this technique provides excellent long-term local control and no patient had urinary leakage/fistula afterward.     

Reconstruction of the right atrium with pulmonary artery homograft after resection of right atrial lipomatosis

We present a case of large right atrial mass due to lipomatous hypertrophy of the interatrial septum and left lower lobe adenocarcinoma. Combined resections of the right atrial mass with reconstruction of the superior atriocaval junction and right atrial free wall defects with pulmonary artery homograft and wedge excision of the lung tumor were performed through median sternotomy.     

4E-binding protein 1: a key molecular "funnel factor" in human cancer with clinical implications

In an attempt to identify molecules that clearly reflect the oncogenic role of cell signaling pathways in human tumors, we propose a concept we term "funnel factor", a factor where several oncogenic signals converge and drive the proliferative signal downstream. In studies done in various tumor types, the expression of key cell signaling factors, including Her1 and Her2 growth factor receptors, as well as the RAS-RAF-mitogen-activated protein kinase and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways was correlated with the associated clinicopathologic characteristics of these tumors. The downstream factors p70, S6, 4E-binding protein 1 (4E-BP1), and eukaryotic translation initiation factor 4E, which play a critical role in the control of protein synthesis, survival, and cell growth, were also analyzed. We found that phosphorylated 4E-BP1 (p-4E-BP1) expression in breast, ovary, and prostate tumors is associated with malignant progression and an adverse prognosis regardless of the upstream oncogenic alterations. Thus, p-4E-BP1 seems to act as a funnel factor for an essential oncogenic capability of tumor cells, self-sufficiency in growth signals, and could be a highly relevant molecular marker of malignant potential. Further investigation into this concept may identify additional funnel factors in the oncogenic pathways and provide potential therapeutic targets.     

Altered methionine metabolism and global DNA methylation in liver cancer: relationship with genomic instability and prognosis

Mounting evidence underlines the role of genomic hypomethylation in the generation of genomic instability (GI) and tumorigenesis, but whether DNA hypomethylation is required for hepatocellular carcinoma (HCC) development and progression remains unclear. We investigated the correlation between GI and DNA methylation, and influence of methionine metabolism deregulation on these parameters and hepatocarcinogenesis in c-Myc and c-Myc/Tgf-alpha transgenic mice and human HCCs. S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and liver-specific methionine adenosyltransferase (MatI/III) progressively decreased in dysplastic and neoplastic liver lesions developed in c-Myc transgenic mice and in human HCC with better (HCCB) and poorer (HCCP) prognosis (based on patient's survival length). Deregulation of these parameters resulted in a rise of global DNA hypomethylation both in c-Myc and human liver lesions, positively correlated with GI levels in mice and humans, and inversely correlated with the length of survival of HCC patients. No changes in MATI/III and DNA methylation occurred in c-Myc/Tgf-alpha lesions and in a small human HCC subgroup with intermediate prognosis, where a proliferative activity similar to that of c-Myc HCC and HCCB was associated with low apoptosis. Upregulation of genes involved in polyamine synthesis, methionine salvage and downregulation of polyamine negative regulator OAZ1, was highest in c-Myc/Tgf-alpha HCCs and HCCP. Our results indicate that alterations in the activity of MAT/I/III, and extent of DNA hypomethylation and GI are prognostic markers for human HCC. However, a small human HCC subgroup, as c-Myc/Tgf-alpha tumors, may develop in the absence of alterations in DNA methylation.     

Identification and chromosome mapping of loci predisposing to colorectal cancer that control Wnt/beta-catenin pathway and progression of early lesions in the rat

Sporadic colorectal cancer (CRC) is a major health concern worldwide. Epidemiologic evidence suggests a polygenic predisposition to CRC, but the genes responsible remain unknown. Here, we performed genome-wide scanning of male (ACI/SegHsd x Wistar-Furth)F2 (AWF2) rats to map susceptibility genes influencing the evolution of early colorectal lesions to adenocarcinoma following 1,2-dimethylhydrazine administration. Phenotypic analysis revealed higher incidence/multiplicity and lower size of adenomas in ACI/SegHsd (ACI) and (ACI/SegHsd x Wistar-Furth)F1 (AWF1) than Wistar-Furth (WF) rats and higher incidence/multiplicity of poorly differentiated adenocarcinomas in WF than ACI rats, with intermediate values in AWF1 rats. Linkage analysis of 138 AWF2 rats identified three loci on chromosomes 4, 15 and 18 in significant linkage with lesion multiplicity that were identified as rat Colon cancer resistance (rCcr) 1, rCcr2 and rCcr3, respectively. Seven other loci on chromosomes 5, 6, 15, 17, 18 and 20 were in suggestive linkage with adenoma/adenocarcinoma multiplicity/surface area. Six of them were identified as rCcr4-9 and a locus on chromosome 5 was identified as a susceptibility locus, rCcs1. Significant interactions between rCcr3 and rCcr6, rCcr6 and rCcr8 and rCcr5 and rCcr9, and four novel epistatic loci controlling multiplicity/size of colorectal lesions were discovered. Apc, located at rCcr3, did not show functional promoter polymorphisms. However, influence of susceptibility/resistance genes on Wnt/beta-catenin pathway was shown by defective beta-catenin inactivation in WF but not in ACI and AWF1 rat adenocarcinomas. These data indicate that inheritance of predisposition to CRC depends on interplays of several genetic factors, and suggest a possible mechanism of polygenic control of CRC progression.     

The elderly with synchronous non-small cell lung cancer and solitary brain metastasis: does palliative thoracic radiotherapy have a useful role?

We evaluated the prognosis associated with advanced age by comparing the clinical features of individuals 65 years of age and older to those of younger patients with single metastasis to the brain alone (SMBA) and simultaneous non-small cell lung cancer (NSCLC), and the potential role of palliative thoracic radiotherapy in this cohort of patients. Our 23-year experience included 72 consecutive (22 elderly and 50 non-elderly) people. Older patients predominantly presented with N0-N1 stage disease and coexisting illness. Univariate analysis showed that younger age (p=0.04) and operative removal of SMBA (p=0.01) were predictive of better survival. However, with multivariate analysis, resection of SMBA remained the sole predictor of prognosis. The application of NSCLC radiotherapy for palliation did not favorably alter outcome. In conclusion, elderly patients with simultaneous NSCLC and SMBA seem to fare less well than their younger counterparts. Moreover, the concurrent application of radiotherapy for palliation of the lung neoplasm was not prognostically advantageous.     

Role of allogeneic bone marrow transplantation from an HLA-identical sibling or a matched unrelated donor in the treatment of children with juvenile chronic myeloid leukaemia

Seven children (age range 1.8–11 years) with juvenile chronic myelomonocytic leukaemia (JCML) received an allogeneic bone marrow transplantation (BMT), four from an HLA-identical sibling and three from a matched unrelated donor. In the four children transplanted using an HLA-identical sibling, conditioning regimen included busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM), whereas graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine-A (Cs-A). The preparative regimen was well tolerated and all patients engrafted promptly. None of the patients have relapsed and all four children remain in haematological remission after an observation time of 7, 24, 25 and 48 months, respectively. Of the three children given BMT from an unrelated volunteer, one was <2 years of age and she received the BU/CY/L-PAM regimen. In view of the increased risk of graft rejection described in patients transplanted from unrelated donors, we chose to prepare the other two patients with fractionated total body irradiation (TBI), thiotepa and CY. Cs-A, short-term methotrexate and Campath-1G in vivo were employed to prevent GVHD in this group of patients. Graft failure with autologous reconstitution of haemopoiesis occurred in the child given the chemotherapy-based regimen. One of the two girls given TBI relapsed after BMT; therefore only one of the three patients who received a marrow transplant from a matched unrelated donor survives in complete haematological remission 10 months after BMT. Our study suggests that the conditioning regimen we employed for allogeneic BMT from a compatible sibling is an effective means of eradicating the leukaemic clone. In our experience, results obtained using unrelated donors are less satisfactory and, at present, the use of such donors seems to be riskier and associated with a lower success rate as compared with BMT from an HLA-identical sibling.     

Immunohistochemistry differentiates papillary thyroid carcinoma arising in ectopic thyroid tissue from secondary lymph node metastases.

OBJECTIVE: To verify whether immunohistochemistry might be useful in the distinction between a true laterocervical metastasis of an undetected thyroid carcinoma and a primary tumor outside the gland. DESIGN: Galectin-3, cytokeratin 19, and HBME-1 were assessed in six cases (group A) of laterocervical masses harboring papillary thyroid carcinoma (PTC) but without a thyroid tumor, and in eight cases (group B) showing PTC both in the thyroid and in the laterocervical masses. In both groups, normal-looking follicles adjacent to the laterocervical neoplasia were present. MAIN OUTCOME: We found that the apparently normal follicles in group A were negative for all the antibodies, while group B showed strong and diffuse positive immunostaining. The neoplastic areas were always positive for all the antibodies in both groups. CONCLUSION: Even if immunohistochemical patterns of residual follicles of group B are very well differentiated that they resemble normal thyroid parenchyma, they may well be metastatic carcinomas. On the contrary, the presence of morphologically and immunohistochemically normal-looking follicles in group A, with no intrathyroid tumor, suggests that the primary PTC might possibly develop in the ectopic thyroid tissue. In cases showing morphologically and immunohistochemically normal-looking follicles in laterocervical masses, these findings might lead to a reduction of the overdiagnosis of metastatic disease of an undetected carcinoma.     

Exploring personality clusters among parents of ED subjects. Relationship with parents' psychopathology,attachment, and family dynamics

Background

Eating disorders are some of the most difficult mental disorders to treat and manage. Family interacts with genetic dispositions and other pathogenic factors, and may influence the outburst, development and outcome of EDs. The present study explores with a cluster analysis the personality traits of parents of ED subjects.

Methods

One-hundred-eight mothers and 104 fathers were tested with Temperament Character Inventory (TCI), Eating Disorder Inventory-2 (EDI-2), State–Trait Anger Expression Inventory (STAX), Family Assessment Device (FAD), Attachment Style Questionnaire (ASQ), Symptom Questionnaire (SQ), Psychological Well-Being scales (PWB). The cluster distribution of parents based on personality traits was explored. Parents' clusters TCI scores were compared as regards personality, psychopathology, attachment and family features. Cross distribution of temperament and character clusters in mothers and fathers, among couples and ED diagnoses of the daughters was explored.

Results

Two clusters of mothers and fathers were identified with temperament clustering. Character traits led to two mothers and three fathers clusters. Mothers temperament cluster 1 (MTC1) correspond to a explosive/adventurous profile, MTC2 to a cautious/passive-dependent profile. Fathers temperament cluster 1 (FTC1) was explosive/methodic, FTC2 was independent/methodic. Character clustering distinguished very immature mothers (MCC1) and majority (65%) of character mature mothers with low self-transcendence (MCC2). A third of fathers was severely immature (FCC1), a third impaired as regards relationships (poor cooperativeness and self-transcendence; FCC2), and one third character mature fathers with low self-transcendence (FCC3). Each cluster evidences specific psychopathology and attachment characteristics. FTC1 was more frequently associated with character immaturity. No significant clusters' cross correlation was found in parental couples.

Conclusion

Parents' clusters analyze in depth the univocal picture of prototypical mothers and fathers of EDs. Parents not disturbed as regards personality traits are not exceptions. Since EDs are multifactor disorders family dynamics related to parents' personality may be very relevant or even marginal in their pathogenesis. Conversely, parenting may be negatively influenced by relatively marginal personality malfunctions of parents. The clustering approach to the complexity of personality-related dynamics of ED families improves the picture of ED parents. Psychoeducational, counseling and psychotherapeutic family interventions should consider the specific underlying personality of parents.