Molecular staging of the sentinel lymph node in melanoma patients: correlation with clinical outcome.

BACKGROUND: This study was designed to determine the debated prognostic significance of reverse transcriptase-polymerase chain reaction (RT-PCR) positivity in melanoma patients' sentinel lymph node (SLN) negative by conventional histopathology (PATH). PATIENTS AND METHODS: Patients with primary stage I-II cutaneous melanoma underwent radioguided sentinel lymphadenectomy. Their SLNs were assessed for tyrosinase (Tyr) and melanoma antigens recognized by T-cells (MART-1) mRNA expression using RT-PCR, in parallel with hematoxylin and eosin staining and immunohistochemistry. Tyr and MART-1 expression in the SLNs were correlated with PATH assay results, standard prognostic factors, time to progression and overall survival. RESULTS: Twenty-three of the 124 patients (18.5%) had positive SLNs by both PATH and RT-PCR (PATH+/PCR+). Sixteen patients (13%) were negative by PATH and positive by RT-PCR (PATH-/PCR+). Eighty-five patients (68.5%) had SLNs that were negative by both PATH and RT-PCR (PATH-/PCR-). At a median follow-up of 30 months, recurrence rates among the three cohorts were statistically different (PATH+/PCR+, 60%; PATH-/PCR+, 31%; PATH-/PCR-, 9.4%). Seven of 23 (30%) and two of 16 (12.5%) patients died in the PATH+/PCR+ and PATH-/PCR+ SLN groups, respectively, whereas no patient died in the PATH-/PCR- SLN group. CONCLUSIONS: RT-PCR is more sensitive than PATH to detect SLN metastases and it is a reliable predictor of disease relapse in stage I-II melanoma patients.

Role of electrothrombosis in aneurysm treatment with Guglielmi detachable coils: an in vitro scanning electron microscopic study.

BACKGROUND AND PURPOSE: In the 1990s, the introduction of the Guglielmi detachable coil (GDC) system in clinical practice was followed by extensive clinical use of this endovascular device in the treatment of brain aneurysms. This technology is based on electrothrombosis and electrolytic detachment of platinum coils. Despite the extensive use of this treatment technique, the role of electrothrombosis has not been fully investigated and clarified. An in vitro electron microscopic study of human blood was performed to elucidate the role that electrothrombosis might play in triggering the biologic response of thrombosis of the aneurysmal sac. METHODS: Human blood from five patients was used to fill plastic containers in which GDCs had been deposited. These five patients had subarachnoid hemorrhage and were similar in age and clinical presentation. Electron microscopic studies were performed on GDCs that had been electrically charged and on GDCs that had not. RESULTS: All electron microscopic studies revealed that the electrically charged GDCs were covered by blood elements and fibrin adherent to the surface of the coil. Noncharged GDCs did not have deposits or adhesions of these blood constituents. CONCLUSION: These findings demonstrated that passage of electric current through the GDC induces attraction of blood constituents. This attraction may trigger a thrombotic reaction on the surface of the coil. The greater the time of current application, the more pronounced the cellular reaction and the deposition of fibrin and blood cells on the GDC.

Evidence for a role of the type III-iodothyronine deiodinase in the regulation of 3,5,3'-triiodothyronine content in the human central nervous system.

OBJECTIVE: Thyroid hormone is essential for maintaining normal neurological functions both during development and in adult life. Type III-iodothyronine deiodinase (D3) degrades thyroid hormones by converting thyroxine and 3,5,3'-triiodothyroinine (T3) to inactive metabolites. A regional expression of D3 activity has been observed in the human central nervous system (CNS), and a critical role for D3 has been suggested in the regulation of local T3 content in concert with other enzymes. DESIGN: This study was undertaken to further characterize D3 activity in human CNS and to understand its role in the local regulation of T3 content. METHODS: Autoptic specimens from various areas of human CNS were obtained 6--27 h postmortem from 14 donors who died from cardiovascular accident, neoplastic disease or infectious disease. D3 was determined by measuring the conversion of T3 to 3,3'-diiodothyronine. The T3 content was measured by radioimmunoassay in ethanol extracts, using a specific antiserum. RESULTS: High levels of D3 activity were observed in hippocampus and temporal cortex, lower levels being found in the thalamus, hypothalamus, midbrain cerebellum, parietal and frontal cortex, and brain stem. An inverse relationship between D3 activity and T3 content in these areas was demonstrated. CONCLUSIONS: We have concluded that D3 contributes to the local regulation of T3 content in the human CNS.

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.

Acute histologic and ultrastructural study in one case of human basilar tip aneurysm embolised with guglielmi detachable coils.

SUMMARY: Histologic findings after Guglielmi detachable coils endovascular embolisation have been studied in experimental aneurysms. Few reports describe histopathologic reactions to platinum coils in humans. In this report we describe gross, light microscopic pathology and scanning electron microscopy study of a ruptured basilar tip artery aneurysm in a patient who died 16 hours following coiling.

Primary childhood osteosarcoma: the role of salvage surgery.

The overall results of salvage surgery for lung metastases were evaluated on 174 consecutive patients with primary osteosarcoma below the age of 20, resected in Milan between 1970 and 1988. Seventy-two children treated in the years 1970-1981 were compared with 102 children treated in the years 1982-1988. In the latter period, adjuvant chemotherapy was replaced by neo-adjuvant programs and salvage surgery was applied systematically to all patients with resectable lung metastases through median sternotomy. During the last period, the overall 5 year survival improved significantly from 35% to 58% (P less than 0.001), while the disease free survival rose from 38% to 45% (median 15 vs. 33 months, P = 0.3). The proportion of patients with completely resected lung metastases rose from 17% (7/42) to 55% (27/49), without operative mortality, and the overall survival from detection of lung metastases (including unresected cases) improved from 0 to 28% at 5 years (P less than 0.001). The survival benefit was observed only in the group of children with resected metastases. These data indicate that systematic bilateral pulmonary resection, combined with neoadjuvant chemotherapy, has contributed to improve the final cure rate of childhood osteosarcoma.

The contribution of salvage surgery to the management of childhood osteosarcoma.

Between January 1970 and December 1988, 174 consecutive patients under the age of 20 years with curatively resected primary osteosarcoma were treated at our institute; 72 in the years of 1970 to 1981 and 102 in the years 1982 to 1988. In the latter period, adjuvant chemotherapy was replaced by neoadjuvant programs, and new criteria were adopted for the management of lung metastases, consisting in early bilateral surgical staging and lung resection through median sternotomy for all patients with purely intrathoracic relapse. Follow-up was updated in December 1989. During the last period, the overall 5-year survival improved significantly from 35% to 58% (P less than .001). The disease-free survival rose from 38% to 45% at 5 years, with median values of 15 months versus 33 months, while the frequency of isolated lung metastases dropped from 58% to the actuarial 48%. The proportion of patients who underwent complete resections of their pulmonary metastases rose from 17% (seven of 42) to 55% (27 of 49), without operative mortality. Due to such a high proportion of patients eligible for salvage surgery, the overall survival from detection of lung metastases improved from 0% to 28% at 5 years (P less than .001). Contralateral occult metastases were resected in three of 15 subjects with monolateral clinical lesions, and five patients underwent subsequent lung resections. These data indicate that systematic bilateral pulmonary resection plays an important role in improving the final cure rate of childhood osteosarcoma, beyond the benefit resulting from neoadjuvant chemotherapy.

Surgical treatment of distant metastases in renal cell carcinoma.

Twenty-six patients with metastatic renal cell carcinoma have been submitted to metastatectomy between 1975 and 1986. The actuarial 5-year survival of the 23 patients resected for cure is 31%. The medium disease-free survival was 11 months for the 11 synchronous metastases and 26 months for the 12 metachronous metastases. Three patients with disseminated disease had palliative surgery: 2 for pathologic fractures and one for tracheal compression. All improved after surgery, and survived 7, 16 and 27 months. It is confirmed that surgical resection of solitary or single organ site distant metastases from renal cell carcinoma is justified.

Resection of the proximal humerus and I.O.R. modular prosthesis in the treatment of metastatic lesions.

The authors report a series of 20 patients affected with metastatic lesions of the proximal humerus (19 cases) or scapula (one case) treated by intra-or extra-articular resection of the humerus and successive reconstruction with an I.O.R. type shoulder modular prosthesis. This method is indicated for the treatment of patients with extensive destruction of the epiphysis and cortical bone and limited invasion of the surrounding soft tissues. Prosthetic implant does not contraindicate the use of postoperative radiotherapy, and the cement used to anchor the endomedullary shaft contributes to the sterilization of any metastatic microfoces present by means of an intense esothermic polymerization reaction. The results obtained were satisfactory, with regression of pain and good functional recovery of the limb. There were no postoperative complications.

Benign epiphyseal chondroblastoma adjacent to the femoral intercondylar fossa.

The authors present three cases of epiphyseal chondroblastoma localised adjacent to the femoral intercondylar fossa which proved to be relatively common in a recent review of the case material of the G. Pini Institute of Milan (3 out of 22 cases). They were able to deduce various features of value in diagnosis and treatment which enable a single stage operation to be planned. This consisted of curettage with or without spongy bone transplants, and can be carried out even when the articular cartilage has been breached. The long term results in all three cases were satisfactory.

Giant-cell tumor of bone in skeletally immature patients.

Giant-cell tumor of bone is predominantly an affliction of adults and is rarely found in skeletally immature patients. We are reporting six new cases of histologically confirmed giant-cell tumor of bone in patients with radiographically open epiphyseal plates. These patients account for 1.8 per cent of the 326 giant-cell tumor of bone observed at the Bone Tumor Center of the Istituto Ortopedico Rizzoli in Bologna, Italy.

The treatment of simple bone cysts by topical infiltrations of methylprednisolone acetate: technique and results.

The authors report their experience in the percutaneous treatment of simple bone cysts by intra-cystic local infiltrations of methylprednisolone acetate. In particular, the method adopted, the evolution of the radiologic picture and the results achieved are described. Sixty patients were successfully treated without complications or surgery.

The treatment of infected pseudarthrosis.

Modern tendencies in the treatment of infected pseudarthrosis are discussed and compared with the methods of the recent past. Seventy four cases are analysed in detail. Fifty three were in the tibia, twenty six of which were treated by a standard modern technique consisting of osteomuscular decortication, excision of infected tissues and necrotic bone, external fixation and if necessary the addition of autoplastic cancellous grafts. The main purpose of this study was to analyse these results and assess the validity of this method.