Vulvar metastasis from breast carcinoma: a case report and review of the literature.
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Aged↗
Biomedical subjects
L Mariani
Publications and source records attributed to L Mariani.
New method for expressing survival in cancer. Relation between survival times and patients' age at diagnosis must be taken into account.
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Age of Onset↗
Gene therapy for glioblastoma [correction of gliobestome] multiform: in vivo tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir.
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Antimetabolites↗
Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?
Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases.
Adult↗
The minimal effective exemestane dose for endocrine activity in advanced breast cancer.
Phase I studies have demonstrated that exemestane, an irreversible oral aromatase inhibitor, is able to suppress circulating oestrogen levels. In our previous experience, doses ranging from 2.5 to 25 mg induced a similar suppression of oestrogens. The aim of this study was to identify the minimum effective exemestane dose on the basis of endocrine activity. 20 evaluable postmenopausal advanced breast cancer patients were randomly given exemestane 0.5, 1, 2.5 or 5 mg, in double-blind conditions. Oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), gonadotrophins, sex-hormone binding globulin and dehydroepiandrosterone sulphate serum levels were evaluated from the first day of treatment to the 7th, 14th, 28th and 56th day. Serum E1, E2 and E1S levels were suppressed by all doses starting from day 7; the degree of inhibition versus baseline was 25 up to 72% for E1, 30 up to 62% for E2 and 16 up to 52% for E1S, with higher doses achieving greater suppression; these changes were maintained over time. A significant increase in FSH and LH levels was observed for all doses. Treatment tolerability was satisfactory. The endocrine effects of exemestane appear to be dose related and 0.5 and 1 mg are ineffective for adequately suppressing circulating oestrogens.
Aged↗
Prognostic factors for metachronous contralateral breast cancer: a comparison of the linear Cox regression model and its artificial neural network extension.
The purpose of the present study was to assess prognostic factor for metachronous contralateral recurrence of breast cancer (CBC). Two factors were of particular interest, namely estrogen (ER) and progesterone (PgR) receptors assayed with the biochemical method in primary tumor tissue. Information was obtained from a prospective clinical database for 1763 axillary node-negative women who had received curative surgery, mostly of the conservative type, and followed-up for a median of 82 months. The analysis was performed based on both a standard (linear) Cox model and an artificial neural network (ANN) extension of this model proposed by Faraggi and Simon. Furthermore, to assess the prognostic importance of the factors considered, model predictive ability was computed. In agreement with already published studies, the results of our analysis confirmed the prognostic role of age at surgery, histology, and primary tumor site, in that young patients (< or = 45 years) with tumors of lobular histology or located at inner/central mammary quadrants were at greater risk of developing CBC. ER and PgR were also shown to have a prognostic role. Their effect, however, was not simple in relation to the presence of interactions between ER and age, and between PgR and histology. In fact, ER appeared to play a protective role in young patients, whereas the opposite was true in older women. Higher levels of PgR implied a greater hazard of CBC occurrence in infiltrating duct carcinoma or tumors with an associated extensive intraductal component, and a lower hazard in infiltrating lobular carcinoma or other histotypes. In spite of the above findings, the predictive value of both the standard and ANN Cox models was relatively low, thus suggesting an intrinsic limitation of the prognostic variables considered, rather than their suboptimal modeling. Research for better prognostic variables should therefore continue.
Adult↗
Insular carcinoma: a distinct de novo entity among follicular carcinomas of the thyroid gland.
We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteria of insular carcinoma and 29 cases those of widely invasive follicular carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival showed a significant association between histotype and pT and pN categories. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories were more frequent in the insular carcinoma histotype. By contrast, no significant differences in overall, relative, or visceral metastasis-free survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction-single-strand conformation polymorphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two histotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that insular carcinoma represents a de novo entity distinct from widely invasive follicular carcinoma, that widely invasive follicular carcinoma has biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alterations.
Abdominal Neoplasms↗
Quantitation of in vitro activity of synthetic trans-acting ribozymes using HPLC.
The cleavage activity of synthetic ribozymes needs to be characterized by reliable and rapid methods. A chromatographic method to simultaneously quantitate the amounts of substrate, cleavage fragments and ribozyme is described. The method allows the rapid normalization of analytical data because the sum of the 260-nm peak areas of remaining substrate and obtained fragments is essentially equal to the initial substrate peak area. Moreover, the simultaneous determination of the ribozyme content improves the accuracy of the evaluation of kinetic parameters compared with conventional densitometric methods. Finally, the characterization of two different hammerhead motifs indicated that the method is suitable for a rapid screening of synthetic ribozyme activity.
Base Sequence↗
Arteriovenous shunt measurement during endovascular therapy for cerebrospinal lesions.
PURPOSE: To determine (a) whether superselective angioscintigraphy with technetium-99m macroaggregated albumin (99mTc-MAA) can be used for the evaluation of arteriovenous shunting in tumors and vascular malformations of the head and spine and (b) whether the amount of microparticles shunted is related to diagnosis, lesion size, or angiographic pattern. METHODS: Particles of 99mTc-MAA with a calibrated diameter of 25 to 50 microm were delivered intraarterially in feeders of head and spine tumors and vascular malformations in 38 patients. The first estimation of the proportion of particles reaching the lungs was made on-line in the angiography suite using a hand-held lead-shielded detector. Evaluation of the intralesional shunt (pulmonary shunt index, or PSI) was derived from quantitative gamma camera recordings of tumoral and pulmonary activity after the embolization procedure was complete. RESULTS: The PSI value ranged from 48% to 100% for vascular malformations and vascular tumors (n = 11), 82% to 95% for juvenile angiofibromas (n = 4), 63% to 70% for high-grade gliomas (n = 2), 0% to 50% for renal cell carcinoma metastases (n = 4), 0% to 86% for meningiomas (n = 11), and 0% to 36% for paragangliomas (n = 6). Angiographically, the presence of visible arteriovenous channels was predictive of a high PSI. In contrast, the presence of early venous drainage was associated with a wide PSI range. CONCLUSION: Superselective 99mTc-MAA angioscintigraphy of tumors and vascular malformations of the head and spine is a valuable method for quantifying an intralesional arteriovenous shunt before embolization.
Adolescent↗
[Crisis and evolution in the field of pharmacy?].
A series of events has, recently, attracted the interest of the scientific and the business community, as well as of the general public: 1. Some of the biggest pharmaceutical companies fused to form giant conglomerates with international basis; 2. Established drug production sites have been shut down in Italy without being replaced by new enterprises and 3. Applications to register new drugs in Italy have significantly decreased in favor of the European Patent Office in the UK. These events are considered by the authors as signs of an evolutive crisis of the pharmaceutical industry, where companies try to maximize their economical gains on a world basis. In this process Italy is becoming the target of a progressive extromission from the production phase, but especially from the research/development of new drugs. Changes in the regulations and in the "modus operandi" of our country are necessary and advocated to keep Italy among the leading industrial countries with an "allure" of profitability for international investors.
Community Pharmacy Services↗
Amoebic Liver Abscess in a Sicilian Traveler Returning from Bali.
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Journal Article↗
Gene expression of DNA topoisomerases I, II alpha and II beta and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.
DNA topoisomerases, nuclear enzymes that regulate DNA topology, are recognized as the primary targets of effective anti-tumor drugs. These enzymes may also have a role in the repair of DNA damage induced by alkylating agents and platinum compounds; therefore, their expression may be a determinant of tumor response to chemotherapy. Our study was undertaken in an attempt to establish a correlation between the enzyme expression and response of ovarian cancer to cisplatin-based chemotherapy. The expression of topoisomerase I, II alpha and II beta genes was assessed by RNase protection assay in tumor specimens obtained from 37 untreated patients with advanced epithelial ovarian cancer at initial surgery and from 13 pre-treated patients at subsequent laparotomy. The expression levels were compared with those found in 5 specimens from benign ovarian tissue and 5 specimens from normal ovarian tissue. The expression levels in untreated patients were used to establish a correlation with response to high-dose cisplatin therapy. A significant intertumor variability of mRNA expression was noted for all the genes examined. However, a comparison of median values indicated a remarkable increase of expression in malignant tumors over benign or normal tissues only for topoisomerase II alpha. This change is not related to alterations or amplification of topoisomerase II alpha gene. Interestingly, a correlation was found between tumor response to chemotherapy and the expression level of the isoform alpha (but not of topoisomerase II beta and topoisomerase I). The observed correlation suggests a contribution of the enzyme in determining tumor sensitivity. Alternatively, increased expression levels of the alpha isoenzyme gene in responsive tumors might reflect higher fractions of proliferating tumor cells that may be more drug-sensitive than resting cells.
Adult↗
A dose-finding study of lanreotide (a somatostatin analog) in patients with colorectal carcinoma.
BACKGROUND: Laboratory data suggest that insulin-like growth factor-1 (IGF-1) may stimulate the growth of different human tumors. At least in acromegalic patients, somatostatin (SMS) analogs, such as lanreotide, suppress the serum levels of growth hormone (GH) and IGF-1. METHODS: To evaluate the tolerability and biologic activity of different doses of lanreotide in patients with advanced colorectal carcinoma, consecutive groups of 3 patients each were subcutaneous treated with lanreotide at doses of 1, 2, 3, 4, 5, or 6 mg three times a day for 2 months. In the event of Grade 3 side effects, 3 additional patients were treated with the same dose before the next dose escalation. Serum samples were obtained on Days 0, 15, 30, and 60 for serum GH, IGF-1, and lanreotide assessment. RESULTS: Twenty-four patients were enrolled and all were evaluable. Except for the 3 and 6 mg doses, for which the observation of a Grade 3 side effect required that an additional three patients be treated, it was sufficient to treat 3 patients at each dose. The overall incidence of side effects was as follows: changes in bowel habits, 83%; abdominal cramps, 79%; diarrhea, 17%; vomiting, 17%; nausea, 21%; steatorrhea, 78%; hyperglycemia, 35%; laboratory hypothyroidism, 39%; gallstones, 13%; and weight loss, 17%. No evidence of an increase in the incidence, intensity, or duration of side effects was observed with dose escalation. Serum IGF-1 levels were as follows: Day 15: 63%, 60%, and 67% of the baseline values for the low (1-2 mg), intermediate (3-4 mg), and high (5-6 mg) dose groups, respectively; Day 30: 63%, 59%, and 51%, respectively; and Day 60: 73%, 69%, and 47%, respectively. Serum lanreotide levels declined during treatment in all of the dose groups (90 ng/mL on Day 15, and 35 ng/mL on Day 60 for the 5-6 mg group; 10 ng/mL on Day 15, and 1.5 ng/mL on Day 60 for the 1-2 mg group). No antitumor activity or tumor marker reduction was observed. CONCLUSIONS: No increase in toxicity was observed when subcutaneous lanreotide doses were escalated to 6 mg three times a day for 2 months. The highest doses seemed to maintain reduced serum IGF-1 levels; with the lowest doses, a "rebound" in serum IGF-1 levels was observed during treatment. Nevertheless, intermittent subcutaneous injections do not ensure constant serum drug concentrations over time.
Adult↗
Results of a breast-cancer-surgery trial compared with observational data from routine practice.
BACKGROUND: The strength of randomised controlled trials (RCTs) is that they allow investigators to draw reliable inferences about treatment differences; physicians can then make a choice between different options. Their weakness is that they are conducted on a set of patients who cannot be regarded as a random sample from the population that will be treated outside the trial. Observational data collected in a prospective clinical database may provide more realistic estimates. METHODS: At the Istituto Nazionale de Tumori of Milan an RCT was started in 1973 (MI1) in which Halsted mastectomy was compared with quadrantectomy plus axillary dissection and radiotherapy (QUART), a breast conserving treatment, for "early-stage" primary breast cancer. In addition, a prospective clinical database was established to collect, in standard format, information on all women undergoing breast conservation thereafter and followed up at the Institute. 1760 women were treated with QUART, 350 of them being accrued in the years 1973-80 in the context of the MI1 trial. The remaining 1408 received QUART after the MI1 trial, up to December, 1984. RESULTS: In the years after the trial, the criteria for use of QUART became more liberal. However, after adjustment for baseline characteristics, out-trial patients fared no worse than trial patients in terms of survival or distant metastasis. Out-trial patients did have a slightly higher rate of local recurrence, probably because of subtle and multiple changes in the surgical procedures since the time of the trial. INTERPRETATION: The results of QUART in out-trial patients resembled those reported from research settings. In this instance, the results of clinical trials did not exaggerate the benefits obtainable in routine practice.
Adult↗
Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group.
BACKGROUND: The unsatisfactory control of neuroendocrine tumor growth with chemotherapy and/or interferon (IFN-2a) stimulated us to investigate the role of the somatostatin analogue octreotide (SMS 201.995), which is reported to be highly effective in controlling carcinoid syndrome symptoms. Octreotide has been used in a wide range of doses, and it was postulated that higher doses might lead to an objective response. METHODS: The aim of the present multicenter Phase II study was to determine the safety and efficacy of SMS 201.995 in controlling carcinoids and other neuroendocrine tumors. Fifty-eight patients were treated subcutaneously with 2 sequential doses of the drug (Sandostatina, Sandoz, Inc., S.b.A. Pharmaceuticals, Basel, Switzerland). The first 23 patients received 500 micrograms 3 times a day and the remaining 35 patients received 1000 micrograms 3 times a day. The treatment was continued until the tumor progressed. RESULTS: All of the patients were adequately treated and evaluated. The predominant histotype was carcinoid, although there were instances of medullary thyroid carcinoma, pancreatic islet cell tumors, and Merkel cell carcinoma. Carcinoid syndrome was documented in 16 patients and abnormal urinary 5-hydroxyindoloacetic acid excretion in 15. The median treatment duration was 5 months (range, 2-31 months). The responses were evaluated in three categories: tumor regression for tumor growth control, symptom response, and biochemical response. There was an effect on tumor growth in two patients with carcinoids. Symptomatic control was achieved in 73% of patients and a biochemical response in 77% of patients. In twenty-seven patients, the disease stabilized for at least 6 months (range, 6-32+). The median survival time for all patients was 22 months (range, 1-32+). CONCLUSIONS: In terms of tumor regression, octreotide is disappointing (partial response: 3%); symptomatic response and biochemical control are satisfactory. These data confirm that somatostatin analogues are comparable to interferons in the treatment of carcinoid syndrome, although other efforts are necessary to control tumor regression.
Adenoma, Islet Cell↗
Preoperative embolization of paragangliomas and angiofibromas. Measurement of intratumoral arteriovenous shunts.
OBJECTIVE: To determine if technetium Tc 99m-labeled macroaggregated albumin selective angioscintigraphy enables estimation of microparticle-arteriovenous shunt in branchial paragangliomas and nasopharyngeal angiofibromas. DESIGN: Technetium Tc 99m-labeled macroaggregated albumin particles with calibrated diameters between 25 and 50 microns were administered during selective catheterization of the feeding arteries in 4 branchial paragangliomas (glomus tumors) and 4 nasopharyngeal angiofibromas. Preliminary measures of the activity of the tumor region and of the lungs were obtained in the angiography suite using a hand-held detector. Without changing the position of the microcatheter, definitive embolization was performed. After endovascular treatment, scintigraphy was performed and the pulmonary shunt index was calculated with the use of a gamma camera and a dedicated computer program. RESULTS: The pulmonary shunt index varied between 0% and 36% for branchial paragangliomas (glomus tumors) and between 82% and 95% for angiofibromas. CONCLUSIONS: Our results provide new evidence that the incidence of microparticle-arteriovenous shunt in nasopharyngeal angiofibromas is much higher than in paragangliomas.
Adolescent↗
Cancer of the low and middle rectum: local and distant recurrences, and survival in 350 radically resected patients.
The purpose of this study was to compare local recurrence, distant metastases, and survival rate in 350 patients with cancer of the middle and low rectum who underwent a radical abdominoperineal resection (APER) or a sphincter-saving resection (SSR) in our Institute. There were 257 APER patients and 93 SSR patients, with a median follow-up of 77 months. At 5 years, the estimates in APER and SSR patients were respectively 11% and 30% for the incidence of pelvic recurrence, 18% and 8% for the incidence of distant metastases, and 64% and 73% for overall survival. In the multivariate analysis it was found that Dukes' stage significantly affected pelvic recurrences, distant metastases rate and overall survival; histologic type affected only the pelvic recurrence rate. However, the final outcome of patients following APER or SSR was similar, suggesting that local failure per se does not affect long-term survival.
Adult↗
Non-small-cell lung cancer: detection of mediastinal lymph node metastases by endoscopic ultrasound and CT.
In this prospective study endoscopic ultrasound (EUS) and computed tomography (CT) were evaluated to compare diagnostic accuracy of the two methods. They were performed for nodal staging in selected patients admitted to our institution for non-small-cell lung cancer (NSCLC). From February 1992 to July 1993, 45 patients were recruited for the study when N3 and N2 nodal involvement were excluded on standard chest X-ray. All the patients completed EUS and CT exams for staging before treatment. The results of sensitivity, specificity and accuracy were obtained in 30 patients who underwent surgical treatment with macroscopically radical resection of T and N, which allowed a complete surgical and histological comparison of CT and EUS findings. On a per-patient basis CT results were: sensitivity 63.6%, specificity 78.9% and accuracy of 73.3%; on a nodal station basis sensitivity, specificity and accuracy were 70.0%, 85.1% and 81.6%, respectively. The EUS evaluation showed, on a per-patient basis, values of sensitivity 45.5%, specificity 57.9% and overall diagnostic accuracy of 53.3%. On a nodal station basis the results were 50.0%, 86.6% and 78.2%, respectively. The results obtained in the 30 patients when both techniques were taken in association regarding sensitivity (90.9%), specificity (73.7%) and accuracy (80.0%) on a per-patient basis suggest that the association of EUS and CT offers the best approach for preoperative staging of NSCLC.
Adenocarcinoma↗