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We reviewed our experience to assess the predictive role of preoperative lymphoscintigraphy with regard to the pathological status of sentinel lymph node (sN) in patients with cutaneous melanoma, to optimize the surgical treatment planning with regard to the use of intraoperative frozen section examination of sN. Eighty-eight patients with clinically node-negative cutaneous melanoma pT1b-T4 stage underwent preoperative lymphoscintigraphy for the lymphatic mapping of sN. A lymphoscintigraphic 'score' (from L1 to L5) was developed based on the ratio of radiotracer concentration within sN nodes as compared with the injection site. Our score allowed us to foresee that sN of patients with thick melanomas (T3 and T4) and a low preoperative score (L1-L2-L3) had a 90% expected likelihood (P

Background: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary dissection in breast cancer patients with negative SLNs. Evidence of a similar efficacy, in terms of survival and regional control, of this strategy as compared with axillary resection is based on few clinical trials. In 1998, we started a randomized study comparing the two strategies, and we present here its results. Materials and methods: Patients were randomly assigned to sentinel lymph node biopsy (SLNB) and axillary dissection [axillary lymph node dissection (ALND arm)] or to SLNB plus axillary resection if SLNs contained metastases (SLNB arm). Main end points were overall survival (OS) and axillary recurrence. Results: One hundred and fifteen patients were assigned to the ALND arm and 110 to the SLNB arm. A positive SLN was found in 27 patients in the ALND arm and in 31 in the SLNB arm. Overall accuracy of SLNB was 93.0%. Sensitivity and negative predictive values were 77.1% and 91.1%, respectively. At a median follow-up of 5.5 years, no axillary recurrence was observed in the SLNB arm. OS and event-free survival were not statistically different between the two arms. Conclusions: The SLNB procedure does not appear inferior to conventional ALND for the subset of patients here considered.

The role of elective lymph node dissection (ELND) for treatment of cutaneous melanoma is still debated. Initially, lymphatic mapping technique was performed by an intradermic injection of vital blue dye; subsequently, it was improved by the use of radioguided surgery (RGS). Preliminary experience with this technique proved effective for detection of clinical occult lymph node metastasis; it may also enable the surgeon to perform a selective lymph node dissection (SLND) to concentrate on pathologic node-positive patients for the same potential benefits that have been provided by ELND. We performed sentinel node biopsy on 48 patients with stage pT3N0M0 melanoma. Vital blue dye mapping only was carried out on 39 patients; the remaining nine patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel lymph node (SLN) was identified in 46 of 48 patients (95.8%). Ten patients (20.8%) were found to have metastatic melanoma cells in their SLN(s); all these patients underwent SLND of the affected basin. Our findings confirm that the intraoperative lymphatic mapping of the SLN using both blue dye and radiodetection is an appropriate and simple technique for selecting patients who are more likely to benefit from lymph node dissection.

The authors performed a prospective study in a series of patients undergoing combined general and epidural anaesthesia for major abdominal surgery in order to define if the epidural catheter inserted for postoperative analgesia induced in the short-term (7-8 postoperative days) any cytopathologically appreciable inflammatory response.From April to September 2001, 20 consecutive patients undergoing combined general and epidural anaesthesia for major abdominal surgery at the National Cancer Research Institute and Villa Scassi Hospital (Genoa), were recruited after obtaining Institutional Ethics Committee approval and written consent from the patients. The standard technique for epidural anaesthesia was adopted. Preoperatively, all patients received peridurally a dose test of 3 ml of 2% lidocaine (60 mg) followed by 5 ml of ropivacaine 0.75%, and a continuous infusion of ropivacaine 0.375% (5-10 ml/h; maximal dose=20 ml) intraoperatively. As regards the therapeutic management of postoperative analgesia, patients received a continuous infusion of ropivacaine 0.2% for at least 48 hours and supplemental bolus (2 mg/die) of morphine hydrochloride. The epidural catheter was always removed between the 7th and 8th postoperative day, and it was examined by the pathologist according to the Thin Prep 2000 procedure.The cytopathologic examination of the tip of the epidural catheter gave the following findings: amorphous material without cells (n=10); rare granulocytes and histiocytes (n=6); stromal cells (n=3), and rare lymphocytes (n=1).We were unable to detect any cytopathologically appreciable inflammatory response at the tip of the epidural catheter which could have suggested the occurrence of inflammation in the epidural tissues. Given the positive results of prophylactic epidural administration of small doses of corticosteroids in the reduction of postepidural anaesthesia back pain and their direct membrane action on nociceptive C-fibers, this kind of backache seems to be related to the stimulations of such nociceptors more than to a catheter-related inflammatory response of epidural tissues with possible evolution in peridural fibrosis, as reported following surgical intervention for lumbosacral disease.

The authors report their experience in patients with adjuvant systemic 2-interferon with the aim of defining the effectiveness, side-effects, indications and limitations of this treatment.From January 1989 to December 1996, 123 patients with genital, anorectal and perineal HPV lesions were treated with cryosurgery; adjuvant systemic a2-interferon was administered to 38 of them. There were 76 female and 47 male patients (median age of 29 years, range; 15-56 years). Clinical examinations included: digital rectal examination, head and neck examination, urethral meatus inspection and, in female patients, gynaecological examination; they underwent colposcopylurethroscopy, proctosigmoidoscopy, cystoscopy (in advanced disease); scraping for cytology and PCR analysis, and biopsy for histology. Twenty-three percent of patients had more than one site involved; upper digestive tract involvement was observed in 6.6% and 47% had lesions larger than 6 sqcm. Twenty-five females with genital lesions had esocervical lesions only; ten of them had SIL1, while seven a SIL3.Ninety-eight out of 123 patients (79.7%) were recurrence-free after a median follow-up of 32 months. A recurrence was observed in 25 patients: in univariate analysis, recurrence of disease occurred more frequently in females (p = 0.04), in patients with longer duration of symptoms (p = 0.0002),with wider lesions (p = 0.00015), with head and neck involvement (p0.01), and in HIV-positive patients (p = 0.03). In multivariate analysis, duration of symptoms (p = 0.005), head and neck involvement (p = 0.01), and width of lesion3 sq cm (p = 0.025) were associated with increased riskOur findings confirm the value of cryosurgery in the treatment HPV lesions; it is less traumatic, and gives good aesthetic and functional results; moreover, large lesions may be treated and the depth of cryonecrosis is more suitably adapted. Patients amenable to adjuvant treatment with a2-interferon should have multiorgan involvement, HPV type 16 or 18, lesions3 sqcm, long lasting symptoms (6 months) and presence of SIL.

Recent studies have demonstrated that the sentinel lymph node (sN) can be considered a reliable predictor of axillary lymph node status in breast cancer patients. However, some important issues, such as optimization of the technique for the intraoperative identification of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla still require further elucidation. The objectives of this study was to assess (1) the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, and (2) the correlation between the size of sN metastasis (micrometastasisor = 2 mm; macrometastasis2), primary tumour size, and the status of nonsentinel nodes (nsN) in the axilla.Between October of 1997 and December of 1999, 212 patients with breast cancer (average age: 61 years; range, 40-79 years) underwent sN biopsy before performing standard axillary dissection. In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed.Overall, the sN was identified in 206 of 212 patients (97.1%); at histologic examination of all dissected nodes, 77 of 206 patients had positive nodes (37.3%). The false-negative rate was 6.5% (5/77), the negative predictive value was 96.3% (129/134), and accuracy was 97.6% (201/206). Among 72 patients with positive sN, micrometastases were detected in 21 cases and macrometastases in 51. When micrometastases only were observed, the sN was the exclusive site of nodal metastasis in 17 of 21 cases (80.9%); in the remaining 4 cases (19.1%), nsN metastases were detected in 3 of 14 pT1c patients (21.5%), and 1 of 5 pT2 patients (20%). Macrometastases were detected in patients with tumors classified as pT1b or larger: the sN was the exclusive site of metastasis in 3 of 4 pT1b patients (75%), in 14 of 29 pT1c patients (48.2%), and in 3 of 18 pT2 patients (16.6%). The specific contribution of the two different techniques used in the identification of the sN was evaluated; the detection rate was 73.8% (113 of 153) with Patent Blue-V alone, 94.1% (144 of 153) with RGS alone, and 98.7% (151 of 153) with Patent Blue-V combined with RGS (P0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) with each of the three procedures (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS).Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, due to the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar with each one of the methods assessed. That patients with small tumours (1 cm) and sN micrometastasis are very unlikely to harbour metastasis in nsN should be considered when planning randomised clinical trials aimed at defining the effectiveness of sN guided-axillary dissection.

Several studies have been published describing the techniques of identification of the “sentinel lymph node'’ (SN). There are marked differences in the techniques used by different investigators. Although agreement exists about the tracer particle size and the volume of injection, it is unknown what is the best site where to inject the tracer or the vital dye. The aim of the present study was to define the influence of different sites of injection on imaging of the lymphatic ducts and their SNs. We performed a pilot study in 30 consecutive patients with breast cancer who underwent SN biopsy by means of radioguided surgery and vital blue dye mapping. The patients were divided into six groups of five patients each; each patient was given a subdermal (ID) or peritumoral (IP) injection of radiotracer (300 μCi in 150 mL of 99mTc-HSA microcolloids; Albures, Amersham Sorin) above the tumor site in order to localize the SN. After the identification of the SN, a second injection of radiotracer was performed, which was different in each patient subset. In some cases more than one lymph node appeared on the lymphoscintigraphic scans after the second injection of radiotracer. When the peritumoral route was used it took longer to visualize the lymphatic pathways. For the ID route, injection at the exact skin projection over the tumor is optimal. Internal mammary lymph nodes were identified by both IP (2) and ID (1) injection, irrespective of the quadrant in which the tracer was injected. Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific SN. The subdermal route is more accurate than the intraparenchymal route, as it allows faster identification of the lymphatic vessels and SN. We believe these observations should be taken into account for the proper selection of the injection site of either vital dye or radiopharmaceuticals.

Axillary lymph node status represents the most important prognostic factor in patients with operable breast cancer. A severe limitation of this technique is the relatively high rate of false negative sentinel lymph nodes (>5%). We studied 284 patients suffering from breast cancer; 264 had T1 tumors (16 T1a, 37 T1b and 211 T1c), while 20 had T2 tumors. All patients underwent lymphoscintigraphy 18-h before surgery. At surgery, 0.5 mL of patent blue violet was injected subdermally, and the sentinel lymph node (SN) was searched by gamma probe and by the dye method. The surgically isolated SN was processed for intraoperative and delayed examinations. The SN was successfully identified by the combined radioisotopic procedure and patent blue dye technique in 278/284 cases (97.9%). Analysis of the predictive value of the SN in relation to the status of the axillary lymph nodes was limited to 191 patients undergoing standard axillary dissection irrespective of the SN status. Overall, 63/191 (33%) identified SNs were metastatic, the SN alone being involved in 37/63 (58.7%) patients; a positive axillary status with negative SN was found in 10/73 (13.7%) patients with metastatic involvement. In T1a-T1b patients the SN turned out to be metastatic in 9/53 patients (17.0%). In 7/9 patients the SN was the only site of metastasis, while in 2/9 patients other axillary lymph nodes were found to be metastatic in addition to the SN. None of the 44 patients in whom the SN proved to be non-metastatic showed any metastatic involvement of other axillary lymph nodes. Our results demonstrate a good predictive value of SN biopsy in patients with breast cancer; the predictive value was excellent in those subjects with nodules smaller than 1 cm.

The role of elective lymph node dissection (ELND) for the treatment of cutaneous melanoma has been debated for many years. Actually, the value of ELND is seriously questioned because an increasing of overall survival rates has not been demonstrated. The lymphatic mapping technique, initially performed by an intradermic injection of vital blue dye, subsequently improved by the use of radioguided surgery (RGS), proved effective for the detection of clinical occult lymph node metastasis. We performed a sentinel node biopsy on 71 patients with stage pT2/T3N0M0 melanoma. Vital blue dye mapping alone was performed on 39 patients; the remaining 32 patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel node (SN) was complexively identified in 69/71 (97.2%) patients. Sixteen patients (23.2%) were found to have metastatic melanoma cells in their SN(s); all these patients underwent lymph node dissection of the affected basin. Our experience confirmed that the intraoperative detection of sentinel nodes using both blue dye and radio-guided surgery is an effective and reliable technique for selecting patients to be submitted to lymph node dissection.

On the basis of our previous experience, we designed this study to determine the activity and toxicity of outpatient treatment with autologous tumor-infiltrating lymphocytes (TIL) together with intermediate-dose recombinant interleukin-2 (rIL-2) and low-dose recombinant interferon alfa-2a (rIFN-alpha2a), for patients with metastatic melanoma.Between April 1992 and October 1994, we processed 38 melanoma samples derived from 36 patients with metastases. Proliferative cultures of expanded lymphocytes (TIL) were infused only once into patients with metastatic melanoma. rIL-2 was administered subcutaneously for 1 month, starting on the day of TIL infusion, at an escalating dose of 6-18 x 10(6) IU/m2/day for the first week and at the maximum-tolerated dose for the subsequent 3 weeks and then, after a 15-day interval, for 1 week/month for 3 months. rIFN-alpha2a was administered subcutaneously at 3 X 10(6) IU three times each week until progression.Of 38 melanoma samples, 19 (50%) resulted in proliferative cultures and were infused. The median number of expanded lymphocytes was 18 x 10(9) (range, 1-43 x 10(9)), and the median period of culture was 52 days (range, 45-60). rIL-2 was administered at doses ranging between 6 and 18 x 10(6) IU/m2/day. Toxicity was mild or moderate, and no life-threatening side effects were encountered. Two of 19 treated patients experienced complete responses of their metastatic sites (soft tissue), 10 had stable disease, and 7 showed progressive disease. The response rate was 11% (95% confidence interval, 2-35%).Outpatient treatment with TIL plus rIL-2 and rIFN-alpha2a is feasible, although, within the context of the small sample size, the activity of the combination was no different from the reported activity of any of the components used alone.

From 1981 to 1990, 1003 stage I-II breast cancers underwent surgery at the Division of Surgical Oncology of National Institute for Cancer Research of Genoa. This study described the clinical and pathologic features of these breast cancers. Radical mastectomy was performed in 73.8% of cases and conservative surgery in 26.2% of cases. In the last years the number of conservative treatment has increased. Related to size of tumour, in 1991 80.4% of pT1 performed a conservative surgery. The choice of type of surgery for pT2 tumours depended on the choice of patient and the ratio breast size and tumour size. The five-year overall survival was 85.8% in the group of conservative surgery and 65.3% in the group of radical surgery. The overall survival and relapse free survival have been calculated by Kaplan-Meyer method. Actuarial survival curves were computed according to type of surgery, tumor size, nodal status, hormonal receptors. In our experience the size of tumour was an important prognostic factor. The five years, overall survival was 80.7% in pT1 tumours and 67% in pT2-pT3 tumours (p = 10(-6)). The five-year overall survival in negative nodes patients was 80.5%. Conversely in patients with more than ten nodal metastases was 29.5%. The data reported in the present study were no different as in previous studies.

The new combination of ifosfamide and vinorelbine was evaluated in a phase II study of patients with metastatic breast cancer. All the patients had evaluable or measurable lesions resistant to the combination of cyclophosphamide, epidoxorubicin and 5-fluorouracil. Out of 25 patients entered the trial, 7 achieved an objective response (28%) (95% C.I. 12-49.3). Ten patients (40%) experienced stable disease and the remaining patients (30%) progressive disease. The median time to progression was 4 months (range 2-12+). The activity of the ifosfamide-vinorelbine combination has been demonstrated and the toxicity was acceptable.

The authors have examined two separate series of samples from 33 and 23 anti-HIV positive patients with persistent generalized lymphadenopathy (PGL) undergoing lymphnode biopsy. For the first group of patients, the aim was to evaluate the diagnostic and prognostic correlation between clinical and laboratory features and histologic findings. For the second group, an assessment was made of the indications for lymphnode biopsy as determined by the rate of positive histopathologic findings. Histologic alterations were classified into four types according to Ràcz, without knowledge of clinical and laboratory data. At the time of biopsy, the first sample (n = 33) included 21 lymphadenopathy associated syndrome (LAS) (64%), 6 ARC (18%), and 6 AIDS (18%) patients; a significant prevalence of type 1 histologic features was evident in LAS/ARC patients, while type 4 was exclusively present in the AIDS group. These preliminary results suggested that only symptomatic anti-HIV positive patients (ARC/AIDS) should have been selected for lymphnode biopsy, because of the expected high rate of opportunistic infections, malignant lymphoma, or Kaposi's sarcoma (KS) in this specific subset of patients. Actually, in the second sample of 23 patients (ARC = 8: AIDS = 15) the detection rate of AIDS-related neoplasms included ten Kaposi's sarcoma and three Hodgkin's disease. These findings suggest that diagnostic lymphnode biopsies should be limited to selected anti-HIV positive patients with evidence of AIDS-related neoplasms or treatable opportunistic infections, or for the purpose of detecting histopathologic features of prognostic significance.

An investigation on smoking habits of teachers of secondary and high schools allowed the collection of very interesting and useful data for the organization of post-graduate up-date courses and health education programs. Smokers' proportion remains still high, as 35% of males and 30% of females teachers are smokers; this situation is different in other countries, where an inverse relationship exists between smoking habit and economic welfare and cultural level. The number of daily-cigarettes was rather low only in females teachers, as 50% smoked less than 5-10 daily-cigarettes. Teachers' interviews suggested the high degree of interest in the organization of health education programs and courses on smoking, with special regard to the courses on smoking, with special regard to the methodology that is required for prevention programs in the school. The high attendance to the courses, the quantity and quality of teachers' reports on these problems and the practical application in school environment of these theoretical concepts confirmed the reliability and effectiveness of this methodologic approach.

A controlled study was carried out on 60 patients undergoing laparotomy to assess the role of a thymic factor (TP-1 Serono) in the prevention of postoperative infections. All patients entering the study were preoperatively shown to be at risk of sepsis on the basis of the response to skin multitest system for assay of delayed hypersensitivity (Multitest C.M.I. System). The patients were also postoperatively monitored with the same system. The lower incidence of infections in patients treated with the thymic factor with respect to untreated patients (p less than 0.05) and the postoperative response to skin tests have confirmed the efficacy of the thymic factor under study in the prevention of postoperative infections.

A study on 285 students and teachers of a nurse professional school was undertaken in two hospital of Genoa. A questionnaire proposed by World Health Organization and by Italian League Against Cancer was employed to collect data on smoking habits and behaviour. Subjects included in the present study were selectively chosen as they are in a transitional phase between school application and working environment within the hospital practice. Although these sample of hospital personnel showed a slow trend toward quit smoking, the rates of smokers are rather high, both in the youth (55%) and in the teachers. Our results showed that 87% of subjects interview agreed with the necessity to avoid smoking within the hospital environment; young nurses generally lack a specific knowledge about the hazard of smoking and more detailed information is requested for a correct education and prevention of patients' health.

Twenty-two patients undergoing major head and neck surgery were included in a randomized trial to value the efficacy and side effects of parenteral short-term antibiotic prophylaxis of post-operative infections. Two different antibiotic regimens were compared: group A, ceftazidime i.v. (2 g) in three doses (half an hour before surgery, 8 and 16 hours, from the first dose); group B, netilmicin (100 mg) plus clindamycin (600 mg i.v.), following the same chronological schedule. Overall infection rate was 18% (4/22): all post-operative infections occurred in group A patients, including one case of wound infection and 3 mixed infections (wound infection associated with lung infection), with a significant reduction of post-operative infection rate in group B patients (p = 0.045; Fisher's exact test).