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Biomedical subjects

G Manca

Publications and source records attributed to G Manca.

32 records · Page 2Linked to original sources
PubMedDate not supplied

Results of a dose-intense phase 1 study of a combination chemotherapy regimen with cisplatin and epidoxorubicin including medroxyprogesterone acetate and recombinant interleukin-2 in patients with inoperable primary lung cancer.

Based on the role of cytokines in the pathogenesis of cancer-related anorexia-cachexia and the ability of progestins, such as medroxyprogesterone acetate, to reduce cytokine production and relieve cancer-related anorexia-cachexia symptoms, the authors designed an open, dose-finding phase I study of a combined chemotherapy regimen (cisplatin [CDDP], epidoxorubicin [EPI]), including recombinant interleukin-2 (IL-2) and medroxyprogesterone acetate for patients with stage IIIB to IV inoperable primary lung cancer. The end points were clinical response and toxicity with definition of dose-limiting toxicity and maximal tolerable dose; relief of cancer-related anorexia-cachexia symptoms; the assessment of patient serum levels of IL-1beta, IL-6, tumor-necrosing factor-alpha (TNF-alpha), and soluble IL-2 receptor (sIL-2R). From March to October 1997, 16 patients (M:F ratio, 14:2; mean age, 60.5 years; age range, 41 to 74 years) were enrolled. All patients were evaluable for toxicity and 14 of them for response. The patients were assigned to increasing dose levels of drugs according to a dose-escalation schedule. The weekly schedule consisted of a combination of CDDP given intravenously on day 1, EPI given intravenously on day 1, 1 g/day medroxyprogesterone acetate given orally on days 1 to 7, and recombinant IL-2 1.8 MIU administered subcutaneously on days 2 to 7 plus 300 microg granulocyte-colony stimulating factor support given subcutaneously on days 2 to 5. Administration of medroxyprogesterone acetate began 1 week before the first cycle. Dose escalation of the drugs was as follows: 30 mg x m2 x week(-1) CDDP and 25 mg x m2 x week(-1) EPI (first level, two patients); 30 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (second level, 2 patients); 40 mg x m2 x week(-1) CDDP and 33 mg x m2 x week(-1) EPI (third level, 6 patients); and 40 mg x m2 x week(-1) CDDP and 40 mg x m2 x week(-1) EPI (fourth level, 6 patients). Six cycles were planned for each patient. The actual dose intensity delivered was more than 80% of the projected dose intensity of all drugs. After six cycles, clinical response (according to World Health Organization criteria), toxicity (according to World Health Organization criteria), Eastern Cooperative Oncology Group (ECOG) performance status, body weight, appetite, and serum levels of cytokines were evaluated. After six cycles, 9 of 14 patients (64.3%) had partial response, 3 of 14 (21.4%) had stable disease, and 2 of 14 (14.3%) had progressive disease, and the objective response rate was 64.3%. ECOG performance status and body weight did not change significantly after treatment, whereas appetite showed an increase that was of borderline statistical significance. Toxicity was acceptable and only hematologic. Dose-limiting toxicity was established at the fourth dose level; consequently, maximal tolerable dose was assessed at the third dose level. Before treatment, the serum levels of IL-1beta, IL-6, and TNF-alpha were significantly greater in the patients than in healthy persons. The comparison between pretreatment and posttreatment serum values of IL-1beta, IL-6, TNF-alpha, and sIL-2R did not reveal significant differences in the patients. Similar results were obtained when the patients were considered as responders (partial response) or non-responders (stable or progressive disease) to therapy. Only IL-6 serum levels were increased (p = 0.014) after treatment.

Adult↗
PubMedDate not supplied

Detection of melanoma cells in peripheral blood and sentinel lymph nodes by RT-PCR analysis: a comparative study with immunohistochemistry.

The presence of lymph node metastases is the best prognostic factor for predicting relapse or survival in melanoma patients. It has been demonstrated that melanoma metastases spread through the first lymph node(s) draining the tumor (sentinel lymph node, SN) to the lymphatic system and that detection of melanoma cells in peripheral blood directly correlates with prognosis in melanoma. To identify lymph node metastases and circulating melanocytes, we developed a single-step reverse transcriptase-polymerase chain reaction assay (RT-PCR) for detection of two melanoma-specific markers: the tyrosinase gene, which encodes an enzyme associated with melanin synthesis, and melanoma antigen-related T-cells, which are present in tumor infiltrating T-lymphocytes. This method detects two tumor cells in a background of 10(7) lymphocytes. Thirty patients with stage I-IV cutaneous melanoma entered the study. Blood samples were taken preoperatively, one month after excision of the primary melanoma lesion and the SN or total lymphadenectomy, and before the start of chemotherapy and every three months thereafter in metastatic patients. SNs were collected from 22 patients, bisected and analyzed by RT-PCR and routine pathological and immunohistochemical tests. The preliminary results indicate that RT-PCR for melanoma markers is a sensitive and valuable method for the detection of micrometastases and for early diagnosis and staging of melanoma.

Adult↗
PubMedDate not supplied

Sentinel node biopsy in melanoma: the experience of Brescia Civic Hospital.

The accuracy of the sentinel node (SN) technique in the evaluation of lymph node involvement in melanoma was evaluated in 71 consecutive patients with localized disease and Breslow index >1 mm. Lymphoscintigraphy identified at least one SN in 70 of the 71 patients (98.5%). The following day 69 patients underwent selective SN excision. The SN was identified by portable probe. One hundred and twenty-two lymph nodes were removed, 14 (11.4%) of which were metastatic in 9 patients (13%). No metastases were found in 40 patients with Breslow <2 mm. Eight of the 9 patients with positive SNs underwent lymphadenectomy of the whole basin and in two patients new metastatic nodes were found. At 4-26 months' follow-up 1 of the 60 patients with negative SN (scalp melanoma with Breslow 6.2 mm) developed bilateral cervical metastatic nodes. Two more patients with Breslow 3.7 and 5 mm, respectively, developed liver and lung metastases. The remaining 57 patients are still disease free. Among the 9 patients with tumor-positive SNs, 1 was lost to follow-up, 3 died and 5 are still alive. Our data confirm the clinical reliability of the SN technique in melanoma; we feel the technique should be considered a standard tool in the evaluation of melanoma patients.

Adolescent↗
PubMedDate not supplied

Gamma probe-guided thoracoscopic surgery of small pulmonary nodules.

Video-assisted thoracic surgery (VATS) is an interesting and emerging procedure for the diagnosis and treatment of peripheral pulmonary nodules. We developed a new radioguided surgical technique for the detection during VATS of pulmonary nodules smaller than 2 cm, situated deep in the lung parenchyma and neither visible nor palpable with endoscopic instruments. The procedure is divided into two phases. Two hours before surgery 0.3 ml of a solution composed of 0.2 mL of 99mTc-labeled human serum albumin microspheres (5-10 MBq) and 0.1 mL of non-ionic contrast is injected into the lesion under CT guidance. Then the patient is submitted to VATS. During thoracoscopy a collimated probe of 11 mm diameter connected to a gamma ray detector is introduced via an 11.5 mm trocar and the pleural surface of the suspected area is scanned. A hot spot indicates the presence of the radiolabeled nodule and hence the area to be resected. We treated 39 patients with small pulmonary nodules (mean size, 8.3 mm; range, 4-19 mm). The patients were 27 men and 12 women (mean age, 60.8 years; range, 13-80 years). Nineteen patients had a history of synchronous or metachronous malignancy. In all cases the nodule was detected and resected and the resection margins were pathologically free of tumor. Histological examination showed 21 benign and 18 malignant lesions (7 metastases and 11 primary lung cancers). Nine patients with a frozen section-based histopathological diagnosis of lung cancer without functional contraindications underwent a completion lobectomy by open surgery in the same surgical session. In conclusion, the radiolocalization of small pulmonary nodules by gamma probe during VATS is a safe and easy procedure, with fewer complications and a lower failure rate than other localization techniques.

Adolescent↗
PubMedDate not supplied

Intraoperative fall in plasma levels of intact parathyroid hormone in patients undergoing parathyroid adenomectomy.

Intraoperative measurement of intact parathyroid hormone (PTH) can be used to evaluate the success of parathyroid surgery in primary hyperparathyroidism associated with parathyroid adenoma. To evaluate this approach we used a modified immunoradiometric assay (IRMA) to study the kinetic patterns of circulating PTH disappearance in 13 patients undergoing adenomectomy for single adenoma. The rapid and the standard assay for PTH measurement in plasma were used and compared. The two methods showed a highly significant correlation (r = 0.995; p < 0.0001). We reported a decrease in PTH to 18.2 +/- 2.30 (mean +/- SEM) from baseline values at 15 minutes after successful parathyroid adenomectomy in the 13 patients. The biphasic pattern of serum PTH clearance was calculated in 8 of the studied patients with a fast phase showing a half-life (T1/2) of 3.99 (SEM 0.464) minutes and a slow phase with a T1/2 of 91.0 (SEM 33.6) minutes. Half the amount of the basal values was reached between 4 and 9 minutes. Our study concludes that the modified IRMA for intraoperative measurement is feasible, reliable and sufficiently precise for low hormone values. Since it may yield information on the half-life of PTH in the circulation, it may play a role in the surgical guidance for total exeresis of hyperfunctioning tissue.

Adenoma↗
PubMedDate not supplied

Relationships betxween Fas expression, activation molecule CD25, and functional activity of tumor-associated lymphomonocytes from neoplastic effusions.

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas bearing cells. In the present study we assessed the expression of Fas, activation molecule interleukin (IL)-2 receptor alpha chain (CD25) and an index of functional activity such as thymidine uptake under mitogen stimulation of tumor associated lymphomonocytes (TALM) from 7 neoplastic effusions of advanced cancer patients. The same parameters were studied in peripheral blood mononuclear cells (PBMC) of 7 patients with cancer of different sites and in 7 normal subjects. The proliferative response to phytohemagglutinin (PHA), measured as [3H]-thymidine uptake, of TALM was significantly lower than that of PBMC of cancer patients. The expression of CD25 on unstimulated fresh TALM was slightly higher than that of PBMC from normal subjects: after 24 h of PHA stimulation the CD25 was expressed both on TALM and PBMC from normal subjects. The expression of Fas was assessed on unstimulated TALM, PBMC from cancer patients and normal subjects immediately after (by 2 h, t0) the cell separation, and at different times (24 h and 48 h) thereafter, and on PHA-stimulated TALM, PBMC from cancer patients and normal subjects after 24 h and 48 h of culture (in RPMI 1640). At all times (t0, 24 h and 48 h) the Fas expression by unstimulated TALM was significantly higher than that of PBMC from normal subjects: the Fas expression by PBMC from cancer patients was roughly in the same range as PBMC from normal subjects. At 24 h the Fas expression by PHA-stimulated TALM was significantly higher than that of PBMC from normal subjects, whereas at 48 h the difference was not significant. The TALM studied by us showed to be functionally defective and expressing relatively high levels of Fas showing the characteristics to be considered as a target for FasL expressing tumor cells, which in this way may escape immune control.

Adult↗
PubMedDate not supplied

[Laparoscopic approach to the "acute" and "chronic" bowel obstruction].

AIM OF THE STUDY: To retrospectively evaluate a series of patients with acute and chronic small bowel obstruction and discuss the indications of laparoscopic vs laparotomic approach and the outcome of both these techniques. PATIENTS AND METHOD: 85 patients with acute and chronic small bowel obstruction who underwent to either emergency or elective surgery since January 1999 up to October 2001 were enrolled. Subjects were divided into three groups: 39 treated with emergency laparotomy (group I), 13 with emergency laparoscopy (group II) and 33 with elective laparoscopy for chronic/subacute obstructions (group III). RESULTS: 1) the most frequent indication of the laparotomic approach was either multiple or major previous surgery as well as neoplastic diseases; 2) patients of the second group had frequently previous either minor or laparoscopic surgery; 3) the incidence of previous emergency surgery were maximum among the III group; 4) both post-operative ileus and mean hospital stay lasted less in the II than in the I group. The mean operative time and the morbidity was equal in the two groups; 5) we observed more intra-operative complications, a higher conversion rate and a longer both post-operative ileus and mean hospital stay in the II than in the III group. CONCLUSIONS: Our data support the role of laparoscopy in patients with chronic/subacute small bowel obstruction. Patients with acute obstruction may undergo laparoscopy after a careful selection, excluding subjects with previous either multiple or major surgery as well as neoplastic diseases. Such results need future confirmations from prospective randomized studies.

Acute Disease↗
PubMedDate not supplied

[Videolaparoscopic adrenalectomy in Conn syndrome. Analysis of 39 case observations].

The authors retrospectively analyse 39 patients affected by Conn's syndrome, which have been observed since 1985, and discuss the results of surgical approach using the new technologies. In particular, the introduction of laparoscopy, technique that has been applied almost exclusively since the last seven years, has revealed being the "gold standard" for the surgical treatment of this disease. The adrenal underlying lesions are indeed almost always monolateral, small in size and present very rarely malignancy in their biological behaviour. Furthermore, the authors, although lacking of personal experience, propose the possibility of a more conservative treatment of the adrenal lesions with a simple "enucleation", whose feasibility also in laparoscopy has recently been shown by some authors. Anyway, the Authors believe that this technique of a partial adrenalectomy could be chosen in selective cases of bilateral adenomas or hyperplasia or in those lesions which are placed in an easily accessible peripheral site.

Adrenalectomy↗