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Biomedical subjects

R Gennari

Publications and source records attributed to R Gennari.

At least 19 recordsLinked to original sources

Early detection of cancer: ideas for a debate.

Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.

Breast Neoplasms↗

Irradiation with standard tangential breast fields in patients treated with conservative surgery and sentinel node biopsy: using a three-dimensional tool to evaluate the first level coverage of the axillary nodes.

Recent data show that axillary coverage can be obtained, but only through a selective CT-based treatment planning, as standard tangential fields are inadequate to deliver therapeutic doses. Currently, the replacement of axillary dissection with new techniques, such as sentinel node (SN) biopsy, makes it necessary to re-address the question about the real role of axillary irradiation, complicated by the differences in the anatomy of dissected and undissected axillary regions. The purpose of this paper is the dosimetric analysis of first axillary level coverage in standard irradiation of 15 breast-cancer patients treated with quadrantectomy and SN biopsy (negative finding). During surgery a clip on the site of the SN was positioned, marking the caudal margin of first axillary level. After the breast treatment plan was completed, the first axillary level was contoured on CT scans, from the site of the surgical clip up to the sternal manubrium, for coverage analysis with dose-volume histograms (DVHs) and three-dimensional isodose visualization. The maximum dose mean ranged from 5% to 80% of the prescribed dose (mean value 48.7%). The mean total dose received by the volume of interest was lower than 40 Gy in all but one patient. No patient had total irradiation of first nodal level; only one patient had 35% of the volume enclosed in the 100% isodose. Our analysis lead to the conclusion that therapeutic doses are not really delivered to first level axillary level nodes by a standard tangential field technique, and that specific treatment planning and beam arrangement are required when adequate coverage is necessary.

Axilla↗

Evaluation of skin perfusion after nipple-sparing mastectomy by indocyanine green dye. Preliminary results.

The aim of the study was to investigate the blood supply of the normal nipple areola complex (NAC) and the spared areola complex after a nipple-sparing mastectomy using the analysis of the fluorescence from the indocianine green dye (ICG) injection. Between December 2002 and July 2003 we performed the ICG analysis in 10 cases of healthy breasts and in 9 patients after a nipple-sparing mastectomy and one patient after subcutaneous mastectomy. In all cases, the resulting fluorescence was measured in three different zones: nipple, areola, surrounding mammary skin. Three parameters of the fluorescence curve (slope, maximum intensity, time to achieve a maximum level) were recorded. On the healthy breast, the nipple showed a very high perfusion as compared to the other zones. On the contrary, after the mastectomy the fluorescent pattern was completely altered, being the perfusion of the nipple very low. In conclusion, these preliminary results confirm the applicability and the importance of the ICG technique for evaluating the perfusion of the healthy and spared areola after surgery. Because of the small number of patients further studies are needed.

Female↗

The surgical management of elderly cancer patients; recommendations of the SIOG surgical task force.

Although cancer in the elderly is extremely common, few health professionals in oncology are familiar with caring for series of oncogeriatric patients. Surgery is at present the first choice, but is frequently delivered suboptimally: under-treatment is justified by concerns about unsustainable toxicity, whilst over-treatment is explained by the lack of knowledge in optimising preoperative risk assessment. This article summarises the point of view of the Surgical Task Force @ SIOG (International Society for Geriatric Oncology), pointing out differences from, and similarities to, the younger cohorts of cancer patients, and highlighting the latest updates and trends specifically related to senior cancer patients.

Advisory Committees↗

A prospective, randomized, controlled clinical trial of tissue adhesive (2-octylcyanoacrylate) versus standard wound closure in breast surgery.

BACKGROUND: Recent studies suggest that the use of tissue adhesive for closure of both traumatic lacerations and incisional surgical wounds leads to cosmetic outcome comparable to conventional sutures. To date, no studies have investigated tissue adhesive in breast surgery and costs. Our aim was to compare the tissue adhesive 2-octylcyanoacrylate (OCA) with standard suture in breast surgery. METHODS: A prospective randomized study was conducted in which 151 patients were assessed for eligibility, and 133 were randomly allocated to skin closure with OCA adhesive or monofilament suture. Cosmetic outcome with blinded assessment, wound management by the patients, complication rates, and economic outcome were recorded. RESULTS: There was no difference in cosmetic score in the 2 groups, nor in complications at the early, 6-month, and 1-year follow-up. Patient satisfaction with the wound closed with OCA was rated significantly higher when compared with standard suture (P <.0001). The application of the tissue adhesive was significantly faster than that for standard suture (P <.001). In economic terms total costs were less in the tissue adhesive group, mainly due to lower postoperative costs of physician and assistant services (P <.001). CONCLUSIONS: OCA is effective and reliable in skin closure for breast surgery, yielding similar cosmetic results to standard suture. OCA is faster than standard wound closure and offers several practical advantages over suture repair for patients. Cost analysis has found that OCA adhesive can significantly decrease health care costs.

Adult↗

Complete nodal staging in male breast cancer. (Biopsy of axillary and internal mammary sentinel node).

Carcinoma of the male breast is an uncommon phenomenon, accounting for < 1% of all malignancies in men. Searching for a more conservative treatment we introduced in our clinical practice axillary sentinel node biopsy and, if present, sentinel node biopsy of the internal mammary chain. The potential clinical implications of complete nodal staging are far-reaching, and give us a major new opportunity to stratify male patients with breast cancer for appropriate surgery as well as giving valuable prognostic information.

Biopsy↗

Surgical technique of mammosite RTS implant for accelerated radiation delivery in breast conserving surgery.

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence and to shorten the duration of treatment. This article describes the surgical technique of implant of a new device developed with the goal of making breast conserving therapy more widely adopted. Our preliminary results showed that breast conserving therapy, using high dose-rate brachytherapy delivered with this new device as the sole radiation modality, is both technically feasible and well tolerated by the patients with excellent cosmetic results. This new method seems to be an important step forward in the search for a more conservative treatment for women with breast cancer, and for providing a better quality of life.

Brachytherapy↗

Recognizing features that are dissimilar in male and female breast cancer: expression of p21Waf1 and p27Kip1 using an immunohistochemical assay.

BACKGROUND: Male breast cancer (MBC) is an uncommon disease, and most of our current knowledge of its biology, natural history and treatment has been extrapolated from data on the disease in women. Information is still needed on the molecular biological properties of male breast tumors and their predictive relevance. Kinase inhibitor proteins (KIPs) p27Kip1 and p21Waf1 negatively regulate cell cycle progression by preventing the passage of cycling cells from G1 to S phase through G1 cyclin-dependent kinase activation. No studies exist on the role of these factors in male breast carcinoma. PATIENTS AND METHODS: We have retrospectively analyzed the immunohistochemical expression of p21Waf1 and p27Kip1 protein in 27 primary MBC and in 101 female breast cancers (FBC) treated at the European Institute of Oncology between 1997 and 2000. We also assessed sex hormone receptors status, p53, bcl-2 and c-erb-B2 protein expression, and Ki-67 labeling index. RESULTS: We observed a statistically significant difference in the immunostaining of KIPs p27Kip1 and p21Waf1 in male patients compared with females. Expression of p21Waf1 was observed in 19 of the 27 (70.3%) primary MBCs versus 29 of 101 FBC (29%). Fourteen of 22 negative c-erbB-2 MBCs cases expressed immunostaining for p21Waf1 (P = 0.05). p27Kip1 immunoreactivity was been detected in 26 of 27 (96.2%) male breast patients versus 39 of 101 FBC (39.3%) (P = 0.000). Highly positive staining for P27Kip1 was found in 21 of 25 androgen receptor-expressing samples. Higher levels of p27Kip1 were expressed in bcl-2-positive samples (17 of 20). Eighteen of 22 c-erbB-2-negative cases were strongly immunoreactive for p27Kip1. CONCLUSIONS: p27Kip1 and p21Waf1 immunoreactivity is higher in MBCs compared with FBCs. The findings of higher p27Kip1 and p21Waf1 immunostaining may be an additional predictive factor in MBC. These biological features could be possible indicators for different biological pathways in the tumorigenesis of MBCs.

Adult↗

Use of technetium-99m-labeled colloid albumin for preoperative and intraoperative localization of nonpalpable breast lesions.

BACKGROUND: Management of clinically occult breast lesions is still a major point of debate. Several techniques (eg, skin projection, guidewire localization) have been proposed, but all of them have technical limitations. STUDY DESIGN: The aim of this study was to assess the efficacy of a new method to locate occult breast lesions using technetium-99m (99mTc)-labeled colloid particles of human serum albumin (radioguided occult lesion localization). We studied 647 consecutive patients (mean age 51.3 years; range 25 to 77 years) with nonpalpable breast lesions detected mammographically or by ultrasonography. Within 24 hours before operation, 3.7 MBq (0.1 mCi) of 99mTc-labeled colloid was injected directly into the center of the lesion using stereotactic mammographic guidance (when only microcalcifications were present) or ultrasonographic guidance (for opacities). Excision biopsy was performed with a gamma-detecting probe. After excision, the area was checked for residual radioactivity and the specimen was radiographed to verify complete removal of the lesion. The material was then sent for pathologic examination. The absorbed dose to the inoculated area and the external irradiation to staff were also determined. RESULTS: In all 647 patients, the "hot spot" was located easily and quickly. X-ray and scintigraphy of the specimen verified the presence and centricity of the lesion in all patients but three (99.5%). Pathologic examination revealed 340 cancer lesions (52.6%). Of these patients, 339 (99.7%) were treated by breast-conserving operations and one (0.3%) received a modified radical mastectomy. No major surgical or postoperative complications were encountered. No recurrences were documented during follow-up. The absorbed dose to the breast and other tissue was negligible (0.03 +/- 0.02 mGy/MBq), as was the dose to the surgeon's hands (7.5 +/- 5.0 microSv/h). The latter dose represents 0.015% and 0.002% of the recommended limits of the European Community for the general population and for exposed workers, respectively. CONCLUSIONS: Radioguided occult lesion localization seems to offer a simple and reliable method to locate occult breast lesions with a gamma-detecting probe, allowing complete removal of the lesion in 99.5% of patients. Because of the small quantity of radioactivity, the procedure is safe for both patients and medical staff.

Adult↗

Sentinel node localization in primary melanoma: preoperative dynamic lymphoscintigraphy, intraoperative gamma probe, and vital dye guidance.

BACKGROUND: Sentinel node (SN) biopsy can be used to select patients with primary melanoma for therapeutic lymphadenectomy. The aim of the study was to assess the efficacy of 3 methods to locate the SN: preoperative dynamic lymphoscintigraphy, intraoperative patent blue dye (PBD), and gamma-detecting probe (GDP). METHODS: We studied 133 patients with cutaneous melanoma and clinically negative lymph nodes. Within 24 hours before surgery, colloid labeled with technetium 99m was injected intradermally around the site of the primary melanoma. The patients were studied before their operations by using dynamic lymphoscintigraphy. A total of 208 SNs were found in 164 lymph node basins. In addition, all the patients had PBD injected immediately before the surgical procedure. When the blue-stained node was identified intraoperatively, its radioactivity level was measured with the GDP. In the absence of blue coloration, the GDP was used to trace the SN. RESULTS: Of 208 SNs, 168 (80.8%) were identified in the regional draining basin during intraoperative lymphatic mapping by using PBD. By using the GDP method, 202 (97.1%) of 208 were identified (GDP vs PBD; P < .01). By combining the 2 methods, 206 (99%) of 208 SNs were detected. Of the 133 patients, 29 (21.8%) had pathologically positive SNs, and were subsequently subjected to regional lymphadenectomy. In 26 (89.7%) of 29 patients, the SN was the only node with metastasis. Three cases (10.3%) of recurrence in patients with microscopic SN metastasis and 7 cases (6.7%) of recurrence in patients without SN metastasis were found during a median follow-up of 566 days. CONCLUSIONS: Preoperative dynamic lymphoscintigraphy and intraoperative mapping with PBD and GDP offer simple and reliable methods of staging regional lymph nodes without subjecting every patient to a regional lymphadenectomy.

Adolescent↗

An elderly patient with advanced locoregional melanoma.

There is no consensus on the management of cancer in elderly patients and age per se should not be the sole factor in the decision-making process. We present a case of regional metastatic melanoma in an 83-year-old patient who received either untested or inadequate treatments. The general condition and stage of the disease, rather than chronological age alone, should be the determinant factor.

Age Factors↗

Sentinel node localisation: A new prospective in the treatment of nodal melanoma metastases.

Sentinel node (SN) mapping and biopsy is a procedure that accurately stages the regional lymph node (LN) basin. Defined patterns of lymphatic drainage allow intraoperative determination of the first (sentinel) lymph node in the regional basin, and the absence of metastatic disease in the SN accurately reflects the absence of melanoma in the remaining regional nodes. The use of radiocolloid and a hand-held gamma detecting probe (GDP) together with a vital blue dye provides optimal results, and allows for the successful identification of the SN in over 99% of the procedures. Close collaboration between surgeons, nuclear radiologists and pathologists is required to ensure optimal results. Examination of serially sectioned SNs by hematoxylin-eosin staining (H&E), immunohistochemical staining and perhaps in the near future RT-PCR should reduce the number of patients with missed microscopic melanoma in the regional lymph nodes. Furthermore, the survival benefit recently reported in patients with melanoma metastatic to regional nodes using high dose of interferon alpha-2b signals that the surgeons should aggressively examine patients for the presence of occult regional melanoma metastases. Intraoperative SN mapping and SN biopsy are cost-effective procedures that allows accurate identification of regional lymph nodes that contain metastatic melanoma.

Adolescent↗

Sentinel node localization in cutaneous melanoma: lymphoscintigraphy with colloids and antibody fragments versus blue dye mapping.

In stage I cutaneous melanoma, biopsy of the first tumour-draining lymph node (sentinel node, SN) may replace routine elective lymph node dissection (ELND). The patent blue dye (PBD) technique has been shown to be an original method for the localization of the SN, but its sensitivity is sometimes unsatisfactory, depending on the basin where the SN is located. We compared three methods to locate the SN: intraoperative PBD mapping, lymphoscintigraphy (LS) with an aspecific tracer (colloid) and LS with a specific tracer (monoclonal antibody, MoAb). Fifty patients with cutaneous melanoma were enrolled in this study. The day before surgery LS was performed following an intradermal injection of 55 MBq technetium-99m-labelled HSA colloidal particles (25 patients: group A) or 220 MBq of 99mTc-F(ab')2 MoAb 225.28 S (25 patients: group B) around the site of the primary lesion. In group B an equal amount of tracer was injected, as a control, in the contralateral site. Early and delayed images were acquired with a gamma camera and SN(s) marked on the skin. In all 50 patients the PBD technique was also performed immediately before surgery. When a blue node was identified intraoperatively, its radioactivity level was measured with a gamma probe. In the absence of blue coloration, the probe alone was used to detect the SN. Lymphoscintigraphic visualization of SNs was possible in 50/50 patients (100%), a total of 73 SNs (38 in group A and 35 in group B) were found, distributed in 55 basins. Gamma probe detection (GPD) allowed the identification of SNs in 49/50 patients (98%), and 72 SNs in 54 basins were localized. By contrast, using PBD, SNs were stained only in 40/50 patients (50 SNs in 40 basins). A tumour-positive SN was histologically proven in 13 patients (26%). In group B, no increase uptake was observed in the seven positive SNs (6/25 patients) compared with the contralateral uninvolved nodes. In conclusion this study demonstrates that LS combined with GPD is a safe method for detecting SNs and is more sensitive than the PBD technique. The use of MoAb fragments did not show any advantage over the non-specific tracer.

Adolescent↗

Effect of dietary ribonucleic acid on bacterial translocationand survival following blood transfusion and thermal injury.

Ribonucleic acid (RNA) has been shown to have a key role in the maintenance of normal cellular function and host resistance to infection. The effect of experimental diets containing RNA on microbial translocation, killing of translocated bacteria and the survival rate of the host was studied in a burn animal model which included immunosuppression. Balb/c mice were fed for 10 days with an RNA supplemented diet (AIN/76A). Control groups were fed with two commercial diets: AIN-76A or Purina chow 5001 (chow). After 10 days of feeding, all animals received an allogenic transfusion. On day 15 the animals were gavaged with 10(10)(14)C radiolabeled or unlabeled Escherichia coli, and given a 20% total body surface area (TBSA) burn injury. Animals gavaged with unlabeled bacteria were observed for survival (n = 60) and animals gavaged with labeled bacteria were sacrificed 4 h post-burn (n = 30) and the mesenteric lymph nodes, liver and spleen were harvested. Slightly less translocation was observed in the liver and spleen of animals fed on RNA diet. Bacterial counts were measured and the percentages of translocated organisms that survived in the tissues were calculated and showed no statistical differences between the three groups. Survival was 45% in RNA group versus 55% in the non-supplemented AIN-76A and 50% in the chow group. It is concluded that a diet enriched in RNA slightly affects bacterial translocation but does not affect survival after severe injury.

Journal Article↗

Arginine, glutamine, and dehydroepiandrosterone reverse the immunosuppressive effect of prednisone during gut-derived sepsis.

OBJECTIVE: Corticosteroids are used broadly in clinical practice but may profoundly impair resistance to infections. In contrast, arginine and glutamine are safe and effective immunonutrients that can improve resistance to infection in both animals and humans. This study assessed whether arginine and/or glutamine, with or without dehydroepiandrosterone, a natural endogenous steroid, could reverse the susceptibility to infection caused by prednisone in a burned animal model. DESIGN: Prospective, randomized study. SETTING: A laboratory approved by the American Association for the Accreditation of Laboratory Animal Care at the Shriners Burns Institute, Cincinnati Unit. SUBJECTS: Adult female Balb/c mice, weighing 18 to 22 g. INTERVENTIONS: Animals were prefed an arginine- and/or glutamine- or a glycine-supplemented diet for 14 days. Dehydroepiandrosterone (25 mg/kg/day) and/or prednisone (10 mg/kg/day) were given on days -4 to 0 before animals were given a gavage of 10(9) 111indium-oxine-radiolabeled or -unlabeled Escherichia coli and 20% total body surface area burn injury. Survival rate and the extent of translocation of E. coli were determined. MEASUREMENTS AND MAIN RESULTS: Feeding with diets supplemented with arginine, glutamine, and arginine plus glutamine and treatment with dehydroepiandrosterone reversed the susceptibility to infections caused by prednisone and burn injury. The beneficial effects were mediated by enhanced killing of translocated bacteria and/or by an improved gut barrier function. CONCLUSIONS: Dietary supplementation can reverse the susceptibility to infections caused by prednisone. Both arginine and glutamine as well as dehydroepiandrosterone may be useful therapeutic agents for preventing infections in steroid-treated patients.

Animals↗

Effects of hyperoxia on bacterial translocation and mortality during gut-derived sepsis.

BACKGROUND: While hyperoxia is commonly used for treating carbon monoxide poisoning, chronic nonhealing ulcers, acute traumatic and chronically ischemic wounds, and refractory osteomyelitis, its efficacy is unproven in numerous clinical situations, including treatment during severe sepsis. OBJECTIVE: To test the effects of hyperoxia on bacterial translocation and mortality during gut-derived sepsis in a clinically relevant model of infection. METHODS: Balb/c mice were gavaged with 10(9) Escherichia coli and subjected to a 20% burn injury. Then, the animals were randomized to receive hyperoxia for different periods of time. Survival and the extent of translocation were determined, as well as intestinal histologic features. RESULTS: Hyperoxia treatment preserved gut morphology and improved gut barrier function, decreasing the amount of bacterial translocation. Short-term (4- or 8-hour) hyperoxia (100% oxygen) treatment improved survival only on day 1 after injury but did not affect the final outcome. Short-term (8-hour) hyperoxia (100% oxygen) plus 5-day 40% oxygen environment significantly improved long-term survival. CONCLUSION: Tissue pO2 may be an important regulator of gut barrier function. Hyperoxia treatment appears to play a major role in preserving gut barrier function.

Animals↗