[Surgical treatment of breast cancer in the elderly]. / Trattamento chirurgico del carcinoma della mammella in età avanzata.

AIM: The aim of this study is to evaluate the prognosis and survival of patients aged over 70 years and affected by breast cancer. METHODS: From January 1994 through December 2000, 56 patients with breast cancer aged 70 years or older were submitted to surgical treatment. Associated diseases were present in 24 patients, while no patient showed distant metastases at the time of hospital admission. All patients underwent breast preserving surgery regardless the tumour size and in 31 subjects out of 56, the surgical procedure was performed under local anesthesia. An axillary lymphectomy was associated in 46 patients. According to the TNM staging system, tumours were classified as follows: 10 T1Nx, 18 T1N0, 9 T1N1, 7 T2N0, 10 T2N1 and 2 T3N1. RESULTS: There was no postoperative mortality and in 6 cases an axillary seroma was observed. Radiotherapy and tamoxifen treatment followed surgery in all cases. The median follow-up was 44 months. Nineteen patients (34%) died during the follow-up: 6 patients of cancer progression with a specific cancer-death of 10.7% while 13 patients (23.2%) died because of concurrent diseases. A local relapse (1.8%) was observed in a single patient 2 years after the primary surgical treatment and, at 3 years, 37 patients (66%) are alive and disease-free. Long-term survival was significantly related to the stage of disease at the time of surgery, while our data do not allow any conclusions concerning the impact of axillary dissection on long-term outcome. CONCLUSIONS: In conclusion, results for breast cancer therapy are comparable in old and young patients and therefore strategies and treatment protocols should be similar, breast preserving surgery followed by radiotherapy and ormonal treatment being ''the gold standard''.

Axillary lymphectomy in breast cancer.

BACKGROUND: The aim of the study was to demonstrate the prognostic value of sentinel node biopsy compared to the sampling of clinically suspected nodes and lymphectomy of the 3 axillary levels. METHODS. From October 1996 to January 1999, 60 patients with breast cancer with a diameter of 4 cm or under using different procedures of axillary lymphadenectomy. Sentinel node biopsy was performed using Giuliano's technique, followed by lymph nodes larger than 5 cm (lymph node sampling) and lastly all axillary lymph nodes (axillary lymphectomy at 3 levels). RESULTS: Sentinel nodes were identified in all patients and a mean of 3 sentinel nodes (range 1-5) were removed during the procedure. Histological analysis showed metastatic sentinel nodes in 21 cases. Lymph node sampling was possible in 43 patients who presented enlarged nodes. The mean number of lymph nodes removed was 6 (range 3-10). Lymph node metastasis was found in 10 patients and of these 7 had a metastatic sentinel node, whereas 3 had presented negative results. Histological tests in all 60 cases of complete axillary lymphectomy showed positive results in 4 cases confirming metastasis present in sentinel nodes. CONCLUSIONS: The results show that the association of lymph node sampling can improve the efficacy of sentinel node dissection, highlighting the rare cases of false negatives. In our study, total axillary lymphectomy did not add any information to the N parameter and was resolutive in a small percentage of cases.

Glucose 6-phosphate transport in fibroblast microsomes from glycogen storage disease type 1b patients: evidence for multiple glucose 6-phosphate transport systems.

In liver endoplasmic reticulum the intralumenal glucose-6-phosphatase activity requires the operation of a glucose 6-phosphate transporter (G6PT1). Mutations in the gene encoding G6PT1 cause glycogen storage disease type 1b, which is characterized by a loss of glucose-6-phosphatase activity and impaired glucose homoeostasis. We describe a novel glucose 6-phosphate (G6P) transport activity in microsomes from human fibroblasts and HeLa cells. This transport activity is unrelated to G6PT1 since: (i) it was similar in microsomes of skin fibroblasts from glycogen storage disease type 1b patients homozygous for mutations of the G6PT1 gene, and in microsomes from human control subjects; (ii) it was insensitive to the G6PT1 inhibitor chlorogenic acid; and (iii) it was equally active towards G6P and glucose 1-phosphate, whereas G6PT1 is highly selective for G6P. Taken together, our results provide evidence for the presence of multiple transporters for G6P (and other hexose phosphoesters) in the endoplasmic reticulum.

[Ambulatory surgical treatment for breast carcinoma]. / Trattamento ambulatoriale del carcinoma della mammella.

BACKGROUND: The aim of the study is to demonstrate the feasibility and the oncologic effectiveness of quadrantectomy plus sentinel node biopsy performed under local anesthesia, and to demonstrate the economic and psychologic advantages. METHODS: From October 1996 to March 2000, 71 patients affected with clinical T1 N0 breast cancer, underwent quadrantectomy or tumor resection plus sentinel node biopsy and clinically suspicion axillary nodes biopsy, under local anesthesia at the Casa di Cura "Villa Mafalda" in Rome. RESULTS: Twenty tumors were T1a, 26 T1b e 25 T1c. A mean of 2 sentinel nodes (range 1-4) and a mean of 8 axillary nodes were removed during the procedure. In 2 cases sentinel nodes were not identified. Intraoperative histologic examination showed metastatic sentinel nodes in 11 cases. An axillary node dissection was performed in all cases (>12 nodes) and no other metastatic nodes were found. In all patients clinically suspected nodes were removed. In two cases no evidence of metastasis was found in sentinel nodes, while histologic examination revealed in a patient micrometastasis in one node, and in another patient two metastatic nodes. CONCLUSIONS: Fifty-three patients rated the overall surgical, anesthetic and recovery experience as "very satisfactory", 13 "satisfactory" and 5 "unsatisfactory". Patients typically expressed their pleasure at the possibility to return home and stressed the ease of recovery.

Bilateral vertebral artery dissection causing a cerebrovascular accident in pregnancy. A case report.

BACKGROUND: Vertebral artery dissection, occurring spontaneously or following a traumatic event, is a cause of posterior circulation stroke in young individuals, including pregnant women. CASE: A 20-year-old, primagravid woman acutely developed headache, right-sided hemiparesis and parasthesias, and blurred vision. Within days she complained of cervical neck pain. Magnetic resonance imaging findings were consistent with a posterior circulation cerebrovascular accident (CVA). An arteriogram, performed to exclude vasculitis, revealed bilateral vertebral artery dissection. No inciting event could be recalled. CONCLUSION: Vascular dissections occur rarely during pregnancy. Spontaneous extracranial vertebral artery dissection itself is very rare in general. Cerebral ischemia can follow vertebral artery dissection. In young patients with CVA, consideration of the diagnosis of vertebral artery dissection followed-by angiography and anticoagulation is an important component of the workup and care.

Rapamycin inhibits activation of ryanodine receptors from skeletal muscle by the fatty acyl CoA-acyl CoA binding protein complex.

We previously showed (Fulceri et al., Biochem. J. 325, 423, 1997) that the fatty acyl CoA ester palmitoyl CoA (PCoA) complexed with a molar excess of its cytosolic binding protein (ACBP) causes a discrete Ca(2+) efflux or allows Ca(2+) release by suboptimal caffeine concentrations, in the Ca(2+)-preloaded terminal cisternae fraction (TC) from rabbit skeletal muscle, by activating ryanodine receptor Ca(2+) release channels (RyRC). We show here that both effects were abolished by pretreating TC with the FKBP12 ligand rapamycin (20 microM). Moreover, rapamycin reversed the Ca(2+) release induced by combined treatment with 3 mM caffeine and the PCoA-ACBP complex. Rapamycin also reduced the Ca(2+)-releasing activity by PCoA alone. Under the above experimental conditions, rapamycin removed FKBP12 from the TC membranes, as revealed by Western blot analysis. We conclude that FKBP12 associated with RyRC in the TC membrane participates in the activation of the Ca(2+) channel by fatty acyl CoA esters.

Absence of mutations in the highest mutability region of the p53 gene in tumour-derived CHEF18 Chinese hamster cells.

A series of independent tumour-derived Chinese hamster CHEF18 cell lines was analyzed for the presence of mutations in the cDNA region (exons 5-9) of the p53 gene, where the great majority of p53 mutations of human tumours accumulate. Since the gene is highly conserved among species, we used two primers designed on the basis of the human cDNA sequence to isolate the cDNA region from total RNA of Chinese hamster cells. The amplified fragments of 614 bp were digested with cleavase I endonuclease and fragment length polymorphism analysis showed that the restriction pattern of the p53 exons 5-9 region of tumour-derived cell lines was identical to that of diploid Chinese hamster CHL fibroblasts. Sequencing of the amplified fragments showed 100% homology between sequences, which demonstrated the absence of p53 mutations in the exons 5-9 cDNA region expected to have the highest mutability. Nevertheless, the antibody DO-7 recognized the presence of a stabilized p53 protein only in tumour-derived cell lines, which indicated that p53 expression correlated with transformed status.

The sensitization of cells treated with O6-methylguanine to alkylation damage is affected by the number of O6-methylguanine-DNA methyltransferase molecules escaped from inactivation.

O6-Methylguanine (MeG) can bind to the active site of O6-methylguanine-DNA methyltransferase (MGMT) as a free base. The subsequent methyl transfer reaction inactivates the repair protein. Hence, MeG is used to deplete the active MGMT pools in Chinese hamster cell lines (CHO) transfected to express varying amounts of human MGMT. After treatment with the free base, a residual population of active protein molecules remains localized mostly in the cytoplasm. Depleted cells are then challenged with the alkylating drug mitozolomide. Genotoxicity of this agent varied among the cell lines, and the compound sensitivity seemed to be regulated by a steady state equilibrium of residual MGMT molecules between nucleus and cytoplasm.

Management of immune thrombocytopenic purpura associated with the antiphospholipid antibody syndrome.

Our two patients had "primary" antiphospholipid antibody syndrome without underlying systemic lupus erythematosus or other systemic autoimmune process, as well as symptomatic immune thrombocytopenic purpura (ITP). The thrombocytopenia did not respond to prolonged courses of corticosteroids and/or immune globulin infusions, but was controlled following splenectomy. The presence of serum antibodies to platelet surface glycoproteins, typical of ITP, could be helpful in the confirmation of both of these disorders in the same patient, rather than secondary thrombocytopenia. Management of such cases is confounded by an increased risk for both bleeding and thrombosis, including fetal death. To reduce the risk of fetal loss and thrombosis, both patients were advised to take aspirin 80 mg daily. The frequency and clinical significance of this association would suggest that patients with ITP should be tested for antiphospholipid antibodies, particularly before pregnancy or surgical procedures. Patients with coexistent antiphospholipid antibody syndrome would be at increased risk for thrombosis in the post-operative period following splenectomy and should be given prophylactic anticoagulation.

Preconception counseling for the primary care physician.

All health care providers that interact with women of childbearing age should understand the potential benefits of preconception counseling and to approach the evaluation in a thorough manner during routine health maintenance visits. With the increased number of patients enrolled in managed care programs, health maintenance visits provide the unique opportunity to educate women contemplating pregnancy regarding the potential influences of their lifestyle and health status on the future pregnancy. It is becoming increasingly apparent that interventions made during the preconception period are just as crucial as the subsequent 9 months of prenatal care to achieve an optimal maternal-fetal outcome. Some guidelines for the preconception evaluation have been provided, and the implications of chronic medical illness on pregnancy have been discussed.

[Results of conservative surgery in T1 breast carcinoma. Our experience in 66 treated cases]. / Risultati della chirurgia conservativa nel carcinoma mammario T1. Nostra esperienza su 66 casi trattati.

Between 1989 and 1991, 66 women affected by breast cancer smaller than 2 cm in diameter, were treated with conservative procedure plus radiotherapy. Conservative procedure consisted in quadrantectomy and axillary dissection of the 3 axillary nodes levels. Neoplasms were grouped according to TNM classification. Eleven were classified as Tis, 9 as T1aN0M0, 12 as T1bN0M0, one case T1bN1M0, 24 as T1cN0M0 and finally 9 as T1cN1M0. Actuarial 5-year survival rate was related to TNM. It has been reported to be 100% in Tis and T1aN0M0 neoplasms; 91.7% in pT1bN0M0 tumors, 95.8% in pT1cN0M0 neoplasms, 55.6% in patients affected with pT1cN1M0 tumors. According to the relationship between receptor status of the neoplasm and survival, this was 88.9% in ER+ and 77.8% in ER- tumors, and 97.1% against 71.4% (p < 0.05) in PR+ and PR- neoplasms respectively. Two patients presented (3%) local recurrence which were treated by means of a tumorectomy and radiotherapy. Both patients are still living and disease free after 6 and 9 months from re-operation.

Growth hormone release during insulin tolerance, clonidine, arginine and growth hormone releasing hormone tests in short normal children and adolescents.

This study was retrospectively performed in 574 short normal children and adolescents [328 underwent insulin tolerance test (ITT), 34 clonidine test (CLON), 64 arginine test (ARG), 19 GHRH test, 52 ITT+CLON, 30 GHRH+CLON, and 47 ITT+CLON+GHRH) in order to evaluate the effect of pubertal stage on GH response to different tests and to identify the most likely mechanism of action of different stimuli. GH peak was higher during GHRH than in all other tests. Sex or start of pubertal development did not cause any GH peak difference. Low-responder (GH peak less than 10 ng/ml) percentages were similar (ITT = 13.5%, CLON = 13.4%, ARG = 13.2%, GHRH = 10.6%) also when the subjects were divided according to sex and pubertal development. ITT+CLON showed discordant results in 42/99 subjects (30/42 = 71.4% were low-responders to ITT and 12/42 = 28.6% to CLON). GH peak appeared earlier during GHRH (85% less than 45 min) and later during CLON (78%: 60-120 min) than during all other tests; GH peak during ITT showed a wide variability of time. Negative correlations were found between GH peak during GHRH and chronological age, height and bone age and during CLON and chronological age. In conclusion our data show that these tests have similar GH secretagogue reliability.

Wakefulness and sleep autonomic dysfunction in diabetics.

Parasympathetic and sympathetic controls on cardiovascular systems were studied during wakefulness and sleep in 8 diabetic patients (3 IDDM and 5 NIDDM), in order to detect the presence of autonomic dysfunction. In particular, cardiovascular assessment during sleep allowed to detect minimal autonomic abnormalities in the absence of a documented pathology during wakefulness.

Tissue CEA as prognostic indicator in a series of 44 cases of colorectal cancer.

The role of tissue CEA determination as a complementary test in the staging of colorectal cancer and monitoring of the marker in the follow-up of patients, is stressed. In a group of 44 colorectal cancer patients, tissue CEA was determined by the immunoperoxidase assay in the apical and cytoplasmic portion of tumor cells, stroma, glandular lumen, and cytoplasm of superficial and deep cells. A correlation has been observed between spread and stage of tumor and CEA localization at the level of the stroma and cytoplasm of deep cells. It has been also evidenced that in all cases where CEA was present in the stroma and cytoplasm of deep cells, high serum levels of the marker were detected.