Re: Vitamin A analogue for breast cancer prevention: a grade of F or incomplete?
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Anticarcinogenic Agents↗
Biomedical subjects
L Mariani
Publications and source records attributed to L Mariani.
Early gastric cancer: unrecognized indicator of multiple malignancies.
The aim of this study was to evaluate the postoperative outcome and occurrence of second primary malignancies in patients who underwent radical resection for early gastric cancer. Altogether 105 patients with early gastric cancer underwent radical resection and were followed up for a median period of 71 months. Overall lethality was analyzed with regard to mortality due to gastric cancer or other causes. Standardized mortality and morbidity ratios were calculated using data from the Tumor Registry of Lombardy. The 5-year survival rate was 82.8% (operative mortality excluded), which was not different from that expected from an age- and sex-matched Italian population. Ten second primary malignancies were identified, giving a standardized mortality ratio of 1.12 and a standardized morbidity ratio of 1.50. Patients undergoing surgery for early gastric cancer (especially the intestinal type) may have a circa 50% higher risk of a second tumor and should be periodically checked for other tumors, mainly in the supramesocolic area.
Female↗
Ribozyme and free alkylated base: a dual approach for sensitizing Mex+ cells to the alkylating antineoplastic drug.
N-alkyl-nitrosoureas and alkyl-triazenes are alkylating antineoplastic drugs, the efficacy of which is strongly affected by the level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). In tumors, MGMT activity reduces the chemotherapeutic potential of alkylating drugs; therefore, efforts have been made to down-regulate the protein. A partial sensitization of Mex+ cells to alkylating drugs has been obtained using either free alkylated bases or oligonucleotides targeted against MGMT mRNA. In the present work, O6-methylguanine and a chemically modified ribozyme, without a cationic liposome as a carrier, were coadministered to CHO47 cells, which express a high level of human MGMT protein. The reduction of MGMT mRNA and protein enhanced the genotoxicity of the alkylating drug mitozolomide. Furthermore, the sensitivity of CHO47 cells is the same as that of CHO5 cells, which lack MGMT protein. These data indicate that a strategy in which both mRNA and protein are degradation targets can be successfully applied to down-regulate the MGMT gene.
Animals↗
Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.
Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.
Adenocarcinoma↗
Changes in gastroduodenal 5-hydroxytryptamine-containing cells induced by dehydroleucodine.
In previous work, we demonstrated that dehydroleucodine (DhL), a lactone isolated from Artemisia douglasiana Besser, prevents gastroduodenal damage induced by absolute ethanol (EtOH). The present study examined the effects of DhL - applied alone or before EtOH - on gastroduodenal cells containing 5-hydroxytryptamine (5-HT), to clarify the mechanism of action of the drug. Mice were divided into four groups: (I) control; (II) DhL; (III) EtOH, and (IV) DhL + EtOH. Stomachs and duodena were studied by immunohistochemistry and image analysis. EtOH decreased the immunopositive cell number and the area occupied by these cells. This effect was prevented by DhL. DhL alone did not affect the gastric immunopositive cell number and area. Duodena treated only with DhL exhibited a reduction of immunopositive cell number, but no change in area was observed. We propose that the drug probably inhibits the release of the inflammatory mediator 5-HT from endocrine cells, acting as a 'cell stabilizer' in response to injury.
Animals↗
Pleomorphic xanthoastrocytoma derived from glioneuronal malformation in a child with intractable epilepsy.
Malformative lesions as well as neoplasms can cause intractable epilepsy in childhood. Even though the neoplastic nature of a lesion is evident in most cases, the distinction can be difficult in some patients. We present the case of a child with intractable epilepsy caused primarily by a glioneuronal malformation. Years after the first surgical intervention, a pleomorphic xanthoastrocytoma evolved from remnants of this lesion. This case suggests that glioneuronal malformations might be precursor lesions of pleomorphic xanthoastrocytomas.
Astrocytoma↗
Content and quality of currently published phase II cancer trials.
PURPOSE: A number of statistical methods have been proposed for the design and analysis of phase II studies based on dichotomous outcomes. To investigate to what extent such methods are in current use, we conducted a survey of published studies. MATERIALS AND METHODS: We identified studies by conducting a computerized literature search of MEDLINE. We considered trials on systemic antineoplastic treatments described as phase II or pilot. The search was limited to articles written in English and published in 1997. RESULTS: Three hundred eight trials were identified. The majority, ie, 295 (95.8%), had been conducted as single-arm studies, with objective tumor response as the primary efficacy end point. An identifiable statistical design was reported for only 58 (19.7%) of these trials. The quality in reporting the statistical design and compliance with the design in carrying out the study or results interpretation were frequently poor. The frequency of reporting the statistical design was not shown to increase over the years of study start and was not associated with sample size or study duration. Instead, a significant association was found with trial results (which were less frequently positive among studies with a statistical design) and with the impact factor of the publishing journal. CONCLUSION: This survey shows that the quality of the statistical component of published phase II cancer trials is generally poor and raises suspicion that low quality is likely to bias study findings. Journals might improve the methodologic standard of published articles through a more vigilant reviewing policy.
Clinical Trials, Phase II as Topic↗
Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer.
Non-palpable breast cancers are often in situ or smaller and have less nodal and distant metastases than palpable lesions. They represent a heterogeneous group of tumours, which may have different prognostic behaviour. We analysed a retrospective series of 982 non-palpable breast cancers assessed histologically at the National Cancer Institute of Milan from 1985 to 1995, following pre-operative mammography-guided localization. The association between mammographic data (parenchymal pattern and findings), patient age and tumour histology was investigated by review of clinical records and statistical modelling. We also investigated the association between the presence or absence of microcalcification as a mammographic finding and pathological tumour characteristics (tumour size, axillary nodes status and grading) or receptor status for oestrogen (ER) and progesterone (PgR). In situ disease or invasive tumour with an intraductal component, whether extensive or not, were commoner in young women and mammography more frequently showed a dense parenchymal pattern and microcalcifications in these cases. In older women (55 years or more), a fatty breast pattern, nodular opacities with or without microcalcifications, and invasive tumours of the ductal, lobular, mixed or other types were closely related. When the relationships between mammographic findings, pathological tumour characteristics and receptor status were investigated for invasive cancers, there was an association between the presence of microcalcifications and less favourable tumour characteristics.
Adult↗
Sellar reconstruction with resorbable vicryl patches, gelatin foam, and fibrin glue in transsphenoidal surgery: a 10-year experience with 376 patients.
OBJECT: Closure of the sella turcica after transsphenoidal surgery is mainly accomplished with autologous muscle fascia and fat or muscle; this requires a second surgical incision. The authors review the results of using resorbable vicryl patches, gelatin foam, and fibrin glue for sellar reconstruction. METHODS: A review was conducted of 376 consecutive patients who underwent surgery for pituitary adenomas, cysts, or subdiaphragmatic craniopharyngiomas in the sella turcica that the senior author (R.W.S.) had performed or directly supervised over the last 10 years. The sellar reconstruction was performed with a commercially available, synthetic absorbable patch composed of polyglactin 910/poly-p-dioxanone, gelatin foam, and fibrin glue. The patch is essentially resorbed in 2 to 3 months and replaced by fibrous collagen tissue. There were 117 small, 112 medium-sized, and 147 large lesions. The overall nonendocrine postoperative morbidity rate was 2.8%, and included visual deterioration, meningitis, secondary epistaxis, nasal septum complication, and cerebrospinal fluid (CSF) leakage. Two patients with macroadenomas needed reoperation for persistent CSF leakage, which comprised 0.5% of the whole series or 0.8% of the 259 patients with medium-sized or large lesions. There was no mortality and no morbidity related to the implanted material, and in particular no delayed empty sella syndrome. CONCLUSIONS: Closure of the sella turcica with a synthetic absorbable vicryl patch, gelatin foam, and fibrin glue after transsphenoidal surgery is safe and very effective in preventing postoperative CSF fistulas. The use of this technique obviates the need for a second surgical incision and shortens the operating time. Because of the progressive resorption of the substitute material, the interpretation of postoperative magnetic resonance studies was not significantly hindered.
Adenoma↗
Sarcoma botryoides of the uterine cervix in a young woman: a case report.
Among the rhabdomyosarcomas, which represent an uncommon neoplasm of mesoderm origin comprising about 1% of all female genital malignancies, sarcoma botryoides (SB) is an embrional variant usually found in the vagina of infants and young children under 16 years of age. The onset of SB from the uterine cervix is very rare with a peak incidence in the second decade; only a few cases have been published in the international literature so far. The authors report a case of embryonal rhabdomyosarcoma of the uterine cervix which occurred in a young woman treated by radical surgery, followed by adjuvant chemotherapy and radiotherapy.
Adult↗
Pseudomixoma peritonei: a case report.
Pseudomixoma Peritonei (PMP) is an uncommon neoplasm characterised by mucinous ascites and multifocal amorphous mucous substances involving the peritoneal surface, omentum and bowel loops. Although the origin of the Pseudomixoma Peritonei is still unclear, it could be due to the perforation of an ovarian mucinous cystoadenoma or an appendiceal mucocele. The further pelvic dissemination of the endotumor material, which adhere itself into the peritoneal surface, may induce an intra-abdominal transformation of the peritoneal mesothelium into mucin-producing tissue. A case of Pseudomyxoma Peritonei (PMP) which occurred in a young woman is reported.
Adult↗
Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer.
BACKGROUND: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies. We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. METHODS: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence were determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. RESULTS: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P =.642) or ipsilateral breast cancer (P =.177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes =.045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0. 92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1. 89). There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. CONCLUSIONS: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.
Adult↗
A phase 1-2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group.
This study has investigated the effects of herpes simplex thymidine kinase gene (HSV-tk) transfer followed by ganciclovir treatment as adjuvant gene therapy to surgical resection in patients with recurrent glioblastoma multiforme (GBM). The study was open and single-arm, and aimed at assessing the feasibility and safety of the technique and indications of antitumor activity. In 48 patients a suspension of retroviral vector-producing cells (VPCs) was administered by intracerebral injection immediately after tumor resection. Intravenous ganciclovir was infused daily 14 to 27 days after surgery. Patients were monitored for adverse events and for life by regular biosafety assaying. Tumor changes were monitored by magnetic resonance imaging (MRI). Reflux during injection was a frequent occurrence but serious adverse events during the treatment period (days 1-27) were few and of a nature not unexpected in this population. One patient experienced transient neurological disorders associated with postganciclovir MRI enhancement. There was no evidence of replication-competent retrovirus in peripheral blood leukocytes or in tissue samples of reresection or autopsy. Vector DNA was shown in the leukocytes of some patients but not in autopsy gonadal samples. The median survival time was 8.6 months, and the 12-month survival rate was 13 of 48 (27%). On MRI studies, tumor recurrence was absent in seven patients for at least 6 months and for at least 12 months in two patients, one of whom remains recurrence free at more than 24 months. Treatment-characteristic images of injection tracks and intracavity hemoglobin were apparent. In conclusion, the gene therapy is feasible and appears to be satisfactorily safe as an adjuvant to the surgical resection of recurrent GBM, but any benefit appears to be marginal. Investigation of the precise effectiveness of this gene therapy requires prospective, controlled studies.
Adult↗
Preoperative radiation therapy for patients with T2-T3 carcinoma of the middle-to-lower rectum.
BACKGROUND: The aim of this study was to determine the effects of preoperative radiation therapy (RT) on the objective responses of patients with rectal carcinoma to their treatment. These effects were assessed with endorectal ultrasound (EUS) evaluation, histopathologic grading of postirradiation tumor mass reduction in the surgical specimen, and analysis of local and distant recurrences. METHODS: Fifty-nine consecutive patients with palpable adenocarcinoma of the rectum, classified by EUS examination as uT2-uT3 (which meant involvement of the muscular layer and the perirectal adipose tissue, respectively), received 45 grays (Gy) over 3 weeks (2 fractions per day of 1.5 Gy each) given as photons supplied through a high-energy linear accelerator (18 MeV) through 3 fields: 1 posterior and 2 opposed lateral. Surgery was scheduled 2-3 weeks after the end of RT and included a sphincter-saving resection (39 patients) and an abdominoperineal resection (20 patients). RESULTS: Greatest tumor dimension, which was evaluated with rectal endoscopy before RT and measurement of the lesion in the fresh specimen, showed a decrease among two-thirds of the patients; the decrease amounted to approximately one-third of the initial measurement. An echoendoscopic downstaging of the T component was observed among 24.5% of the patients. Complete tumor regression occurred in 8.5% of patients, whereas in 69% only the presence of rare residual cancer cells and prominent fibrosis were found at the pathologic examination of the specimen. Finally, the tumor regressed to pT0 and pT1 in 13.6% of the patients. The overall and disease free 2-year survival rates were 94.0% and 73.7%, respectively, for pT2 and pT3 patients, and 100% for those whose tumors regressed to pT0-pT1 after a median follow-up of 2 years. CONCLUSIONS: Hyperfractionated preoperative RT appears to be efficient in achieving tumor shrinkage and destroying the tumor. In this study, the subset of patients with a good response to RT therapy had an excellent clinical outcome at the time of a 2-year follow-up.
Adult↗
A new classification for malignant tumors involving the anterior skull base.
OBJECTIVES: To propose our clinical classification of malignant ethmoid tumors and to compare it with the last American Joint Committee on Cancer (AJCC)-Union Internationale Contre le Cancer (UICC) classification, published in 1997. DESIGN: Retrospective review. SETTING: Tertiary cancer facility. PATIENTS: We evaluated 123 consecutive patients undergoing craniofacial resection for malignant ethmoid tumors involving the anterior skull base. The mean follow-up was 60 months. Fifty-nine patients (48%) presented with recurrent disease after prior therapy. We classified them with a new classification system (Istituto Nazionale per lo Studio e la Cura dei Tumori) based on the most commonly accepted unfavorable prognostic factors (involvement of dura mater; intradural extension; involvement of the orbit and, in particular, of its apex; invasion of maxillary, frontal, and/or sphenoid sinuses; and invasion of the infratemporal fossa and skin. We also classified patients with the AJCC classification published in 1997. MAIN OUTCOME MEASURES: Disease-free status and overall survival rate. To study a possible association with tumor stage, the Cox regression model was adopted. RESULTS: According to our classification, patient distribution by tumor type was T2, n = 46; T3, n = 29; and T4, n = 48 (no T1 tumors were present in the series). For previously untreated patients, 5-year disease-free survival estimates were T2, 57%; T3, 50%; and T4, 13%. For relapses, corresponding figures were T2, 31%; T3, 23%; and T4, 1%. The prognostic difference among stages was statistically significant (P<.001). Similar results were obtained for overall survival. In contrast, patient distribution among different AJCC stages was less balanced, and we failed to detect a significant association with the clinical outcome using this classification. CONCLUSION: We propose the use of our staging system by all those specialists in the field willing to validate the classification and possibly apply it for clinical and investigational purposes.
Adult↗
Anterior craniofacial resection for malignant ethmoid tumors--a series of 91 patients.
BACKGROUND: Anterior craniofacial resection is now recognized as the best treatment for ethmoid tumors involving the cribriform plate with or without invasion of anterior cranial fossa. METHODS: Ninety-one patients underwent an anterior craniofacial resection for ethmoid malignant tumors at the Milan Cancer Institute between 1987 and 1994. The patient population was divided into two sections (30 and 61 patients) based upon some important variants (type of craniotomy, antibiotic treatment, postoperative care). RESULTS: The mean age was 53.4 years (range, 24 to 78 years). There were 62 men and 29 women. Forty-nine patients had a recurrence after previous treatments (surgery and/or radiotherapy). The subdivision by histology was as follows: 50 cases of adenocarcinoma, 16 cases of epidermoid and undifferentiated carcinoma, 8 cases of esthesioneuroblastoma, 5 cases of adenoid cystic carcinoma, 5 cases of melanoma, and 6 rare tumors. The stages (according to our new staging) were as follows: 37 cases with T2, 27 cases with T3, and 27 cases with T4. The mean follow-up was 47 months. Seven patients died after surgery (6 in the first series). The survival at 3 and 5 years was, respectively, 52% and 47%, and the disease-free survival (DFS) was 30% and 24%, with a statistically significant difference at multivariate analysis in favor of patients without prior treatment (p = .033) or T2 versus T3 and T4 (p<.007). CONCLUSIONS: An anterior craniofacial resection should be performed in cases of ethmoid tumors reaching or eroding the cribriform plate. A scrupulous intra- and postoperative approach is necessary to avoid severe complications. The patients often survive for a long time with recurrence ongoing. Our new staging identifies the critical extensions of ethmoid tumors.
Adenocarcinoma↗
Artificial nutrition in cancer patients: which route, what composition?
The state of art of artificial nutrition in depleted cancer patients is reviewed in brief. Because cancer cachexia cannot be equated to simple nutrient deficiency but is due instead to complex metabolic abnormalities, the nutritional effects of total parenteral (TPN) and enteral (EN) nutrition are more limited than in starving subjects. TPN and EN usually prevent further deterioration of the nutritional status, although they are not able to fully reverse a state of depletion. There is evidence that quantitative and qualitative modulation of certain nutrients may obtain better results because of a favorable impact on host metabolism. Research in this field is fully warranted. Moreover, the effects of some substrates on tumor metabolism and tumor growth require further investigation to define a nutritional regimen able to maintain the host metabolism with minimum stimulation of tumor growth.
Cachexia↗
Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features.
Experimental evidence has shown, both in vitro and in animal models, that neoplastic growth and subsequent metastasis formation depend on the tumor's ability to induce an angiogenic switch. This requires a change in the balance of angiogenic stimulators and inhibitors. To assess the potential role of angiogenesis factors in human thyroid tumor growth and spread, we analyzed their expression by semiquantitative RT-PCR and immunohistochemistry in normal thyroid tissues, benign lesions, and different thyroid carcinomas. Compared to normal tissues, in thyroid neoplasias we observed a consistent increase in vascular endothelial growth factor (VEGF), VEGF-C, and angiopoietin-2 and in their tyrosine kinase receptors KDR, Flt-4, and Tek. In particular, we report the overexpression of angiopoietin-2 and VEGF in thyroid tumor progression from a prevascular to a vascular phase. In fact, we found a strong association between tumor size and high levels of VEGF and angiopoietin-2. Furthermore, our results show an increased expression of VEGF-C in lymph node invasive thyroid tumors and, on the other hand, a decrease of thrombospondin-1, an angioinhibitory factor, in thyroid malignancies capable of hematic spread. These results suggest that, in human thyroid tumors, angiogenesis factors seem involved in neoplastic growth and aggressiveness. Moreover, our findings are in keeping with a recent hypothesis that in the presence of VEGF, angiopoietin-2 may collaborate at the front of invading vascular sprouts, serving as an initial angiogenic signal that accompanies tumor growth.
Angiogenesis Inducing Agents↗