Is it possible to obtain a presurgical Lasmar score for hysteroscopic myomectomy by ultrasound alone?

OBJECTIVE: To determine whether a Lasmar score obtained entirely by the use of two-dimensional (2D) and three-dimensional (3D) ultrasound provides results similar to those obtained using the original hysteroscopic technique. METHODS: This was a prospective study performed on a series of patients presenting with symptomatic submucous fibroids and scheduled for hysteroscopic myomectomy. Ultrasound Lasmar scores were obtained by a single physician, a specialist in ultrasonography, in the luteal phase of the menstrual cycle. 3D images were evaluated by offline examination using multiplanar analysis. Classical Lasmar scores were obtained by a different physician, a specialist in hysteroscopy, during the follicular phase of the subsequent cycle. Surgery was performed by a third physician in the follicular phase who also reported a Lasmar score, which we considered as the gold standard. The concordance between group classifications (I-III, relating to difficulty of hysteroscopic resection) according to the three methods used to obtain the Lasmar score (ultrasound, classical and surgery) was calculated using Cohen's κ statistic. RESULTS: Thirty-four women, with a mean age of 43 ± 4.9 years, were enrolled in the study. Thirty-six submucous fibroids were identified by both ultrasound and diagnostic hysteroscopy. The mean diameter of fibroids evaluated was 28 ± 13.2 mm. The concordance between the three methods of classifying patients according to Lasmar score was high: classical vs. surgery, κ = 0.88; ultrasound vs. surgery, κ = 0.93; and classical vs. ultrasound, κ = 0.77. CONCLUSION: The Lasmar score can be obtained solely by ultrasound examination performed in the luteal phase of the menstrual cycle, avoiding office hysteroscopy without a loss of diagnostic accuracy.

Hysteroscopic management of large symptomatic submucous uterine myomas.

STUDY OBJECTIVE: To evaluate the feasibility of hysteroscopic resection of large submucous uterine myomas. DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: Surgery unit of minimally invasive gynecology. PATIENTS: Thirty-three women with submucous myomas 5 cm or larger in diameter with menorrhagia, dysmenorrhea, or infertility. INTERVENTION: Hysteroscopic myomectomy. MEASUREMENTS AND MAIN RESULTS: Satisfaction with the surgery and an improvement in symptoms were the primary outcomes. Possibility of 1-step resection; complication rate, and disease recurrence were also considered. Menorrhagia was the most frequent indication (91%). According to the Wamsteker classification, 84.8% were type II myomas, whereas 93.9% scored 5 or higher according to the classification of Lasmar and colleagues. Mean operating time was 50 minutes (interquartile range, 35-65). One-step excision was achieved in 81.8% of patients. Of 5 women with incomplete resection, 3 needed a second surgery, and 2 were symptom-free. Patients with myomas larger than 5 cm or with a Lasmar score higher than 7 were more likely to undergo a 2-step procedure. In patients with myomas larger than 6 cm, recovery time was significantly longer than in those with smaller myomas. We recorded 3 complications: intravasation, uterine perforation, and postoperative anemia, in 1 patient each; at present, all 3 women are symptom-free. Median (range) follow-up was 10 (6-22) months. Twenty-seven patients (81.2%) reported they were very satisfied; 5 patients (15.2%) were satisfied; and 1 patient (3%) was dissatisfied. CONCLUSIONS: Hysteroscopic myomectomy can be the treatment of choice in symptomatic patients with a submucous myoma with diameter of 6 cm or less. Although this technique raises the possibility that complete resection may require 2 surgical sessions, it is a feasible surgical procedure. However, for myomas 6 cm or larger in diameter, this approach is less attractive. Nevertheless, we believe that all of the limiting criteria defined in the available literature should be evaluated individually, bearing in mind each patient's particular condition and the surgeon's experience and skill.

CT-guided percutaneous transthoracic biopsy in the diagnosis of mediastinal masses: evaluation of 73 procedures.

PURPOSE: This study was performed to evaluate the factors affecting the diagnostic accuracy and rate of complications of CT-guided percutaneous transthoracic needle biopsy of mediastinal masses. MATERIALS AND METHODS: We reviewed 73 consecutive mediastinal biopsies in 70 patients. Final diagnoses were based on a retrospective analysis of surgical outcomes, results of repeat biopsies or findings of imaging and clinical follow-up lasting at least 4 months. Benign and malignant biopsy findings were compared with the final outcomes to determine the diagnostic accuracy of the method. Finally, we analysed the complications. RESULTS: CT-guided percutaneous transthoracic needle biopsy provided adequate samples in 61/73 cases, with a total sample rate of 83.6%. Of these 61 biopsies, 51 yielded a correct diagnosis with specific histological typing, mainly in the case of thymoma and metastasis. Lymphomas were less reliably diagnosed. The overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy values were 83.6%, 100%, 100%, 35.3% and 83.6%, respectively. Pneumothorax was the most common complication (5.5%). CONCLUSIONS: CT-guided percutaneous transthoracic needle biopsy is an easy, reliable and safe procedure that obviates the need for exploratory surgery in medically treatable or unresectable cases. It should be the first invasive procedure in the diagnostic workup of mediastinal masses.

Hypothalamic-pituitary-adrenal axis function and cytokine production in multiple sclerosis with or without interferon-beta treatment.

OBJECTIVES: Pro-inflammatory cytokines mediate brain damage in multiple sclerosis (MS); they can also influence the hypothalamic-pituitary-adrenal (HPA) axis function. We evaluated the possible abnormalities of HPA axis function in relapsing-remitting MS (RR-MS). MATERIAL AND METHODS: IFN-gamma, TNF-alpha and IL-6 production by ex-vivo lymphocytes from 10 normal volunteers and 10 RR-MS patients before and during IFN-beta therapy was assessed; pituitary-adrenal function was evaluated by means of CRH and ACTH stimulation tests. RESULTS: In untreated patients the production of IFN-gamma, TNF-alpha, IL-6 was increased, and was significantly decreased by IFN-beta. Neither basal, nor stimulated ACTH, cortisol, DHEA, DHEAs, 17-alpha-OH-progesterone levels differed between controls and RR-MS patients, both before and during treatment. Moreover, no correlation was found between endocrine and immune parameters. CONCLUSION: In MS the HPA axis function seems normal and not influenced by IFN-beta treatment. This result is discussed in relation to the increased production of pro-inflammatory cytokines found in this disease.

High-dose intravenous immunoglobulin G treatment of myasthenia gravis.

IVIg is a safe and effective adjunctive treatment for myasthenia gravis, but there are no well established guidelines for the use of IVIg in this disease, lacking controlled randomized trials to assess its efficacy in homogeneous group of patients. The main advantages of IVIg are the rapid onset of the effect, the lack of long-term toxicity, and the possibility to reduce the required doses of immunosuppressive drugs. IVIg appears to have a role as an acute treatment in rapidly progressive myasthenia gravis weakness, particularly in situations when therapeutic apheresis is not feasible. In addition, IVIg is safer than plasma exchange (PE) in patients with hypotension or autonomic instability, in children, in patients of older age (>65 years), and in those suffering from sepsis. For these reasons, at present, IVIg are recommended during crises of myasthenia gravis in older patients when PE is contraindicated or not feasible IVIg can be also used as a chronic maintenance therapy when other immunosuppressive treatments have failed or cannot be used. Periodic administration of IVIg on a bimonthly or monthly basis may be able to stabilize chronic, nonresponding patients.

[Anti-GM1 and anti-sulphatide antibodies in systemic idiopathic vasculitis, systemic lupus erythematosus and mixed cryoglobulinaemia: Serum detection and clinical and electrophysiologic correlations]. / Gli anticorpi anti-GM1 ed anti-solfatidi nelle Vasculiti sistemiche primitive, nel Lupus eritematoso sistemico e nella Crioglobulinemia mista: dosaggio sierico e correlazioni clinico-elettromiografiche.

BACKGROUND: In the last two decades increasing interest has been focused on the association between autoimmune polyneuropathies and high titers of anti-nervous serum autoantibodies. High titer of IgG anti-GM1 antibody could be detected in Guillain Barre' syndrome and in chronic painful axonal sensory immune-mediated polyneuropathy. The possible occurrence of anti-nervous autoantibodies in autoimmune diseases not limited to the nervous system is still under study. METHODS: We evaluated 29 patients with systemic lupus erythematosus (SLE), 19 with biopsy-proven renal involvement, 28 patients with mixed IgM-K/IgG polyclonal cryoglobulinaemia (18 with glomerulonephritis) and 19 with small-sized vessel ANCA-associated vasculitis (12 with renal involvement) by using a sensitive immunoenzyme method of autoantibody detection. RESULTS: Compared to controls (1/176+/-1/205; 1:204+/-1:103), we found a significant increase in plasma IgM and IgG anti-GM1 titers (1:643+/-1:531; 1:444+/-1:309) in SLE patients (p<0.0001). We also found IgM (1:3032+/-1:2844) and IgG (1:1560) anti-sulphatide titers to be higher than the control group (p<0.0001). Mean plasma IgM and IgG anti-GM1 titers of the cryoglobulinaemic patients were 1:524+/-1:403 and 1:501+/-1:415, respectively, once again higher than the controls (p<0.0001). Mean plasma IgM and IgG anti-sulphatide titers in this group were 1:1864+/-1:1189 and 1:1350 (p<0.0001). We found idiopathic systemic vasculitis patients to have significantly increased levels of anti-sulphatides IgG class autoantibodies (1:1400; p<0.0001). We found no correlation with the serologic markers for vasculitis or the clinical or histologic extent of renal involvement. Electrophysiologic studies revealed that in 38% of SLE patients (p<0.005), 61% of cryoglobulinaemic patients (p<0.01) and 42% of ANCA-related vasculitic patients (p<0.01) the abnormal titers of antineuronal antibodies were associated with clinical or subclinical evidence of neuropathy. CONCLUSIONS: In patients with systemic idiopathic or secondary vasculitis anti-GM1 and anti-sulphatide antibodies can frequently be found. Their presence should prompt an accurate neurological examination because these serologic abnormalities are significantly associated with neurologic, often subclinical, involvement. Antineuronal reactivity might be the epiphenomenon of primary phylogistic damage, which exposes normally segregated neuronal epitopes or be directly involved in triggering neurological injury.

Modified and improved anti-acetylcholine receptor (AchR) antibody assay: comparison of analytical and clinical performance with conventional anti-AChR antibody assay.

We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3-7.8%) CVs, greater linearity, lower cost, and shorter assay time than the conventional method. ROC curve analysis indicated almost identical specificity and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and conventional assays were also equivalent for blocking anti-AChR Ab assay. Moreover, the modified anti-AChR Ab assay, differently from the conventional assay, allowed us to reveal anti-AChR Ab concentration differences among different clinical grades of MG.

Systemic high-dose recombinant-alpha-2a-interferon therapy modulates lymphokine production in multiple sclerosis.

Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy reduces exacerbation rate and MRI signs of disease activity in relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the possible mechanisms underlying the clinical efficacy of rIFNA in MS, several immunologic studies were performed as a part of a pilot clinical trial. Twenty RR MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Cytokine production by cultured lymphocytes, major histocompatibility complex class II (MHC-II) antigen expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied before therapy, after 6 months of therapy, and 6 months after stopping therapy. rIFNA therapy was associated with reduction of interferon-gamma and tumor necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight, not significant, increase of transforming growth factor-beta 2 or interleukin (IL)-10 production. IL-4 was undetectable in the culture supernatants both before and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+ CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA therapy. After rIFNA administration, IgG level significantly increased both systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients developed neutralizing antibodies against rIFNA during therapy. Six months after stopping therapy all the immunologic changes returned to baseline. These data suggest that the beneficial effect of rIFNA therapy on MS disease activity is probably mediated by a downregulation of proinflammatory cytokine synthesis by PB lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic effects of high-dose systemic rIFNA therapy are temporary and restricted to the period of drug administration.

Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment.

We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.

Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma with a combination of vinorelbine, cisplatin, and 5-fluorouracil: a multicenter phase II trial.

PURPOSE: Vinorelbine has been demonstrated to be active against squamous cell carcinomas of the head/neck (SCHNC) and lung. This multicenter phase II trial was carried out to evaluate the activity and tolerability of the combination of vinorelbine, cisplatin, and 5-fluorouracil given on an outpatient schedule in a series of 80 patients with recurrent SCHNC. PATIENTS AND METHODS: Eighty patients with recurrent and/or metastatic SCHNC were treated with a combination of CDDP 80 mg/m2on day 1, 5-FU 600 mg/m2 as a 4-hour infusion on days 2-5, and vinorelbine 25 mg/m2 on days 2 + 8. This cycle was repeated every 28 days. Most patients had oral cavity, larynx, or oropharynx carcinoma (88%). Forty-seven had previously received surgery alone, two radiotherapy alone, and 31 surgery plus radiotherapy. Seventy-two patients had locoregional recurrency, and eight had distant metastases. RESULTS: According to an intent-to-treat analysis, complete response (CR) of a mean duration of 12.7+ months was achieved in 13% of cases (95% CI 5%-21%), and partial response of 8.3+ months in 45% of patients (95% CI 33%-56%), for an overall response rate of 55% (95% CI 43%-65%). Nine patients (11%) showed no change, and 22 (28%) progressed. Five patients were not evaluable for response and toxicity. CR were seen more frequently in patients pretreated with only surgery than in those who had also received radiotherapy (15% vs. 9%; p = 0.7). No statistically significant differences in response rate according to site of primary tumor were found (p = 0.8, NS). The received dose intensities of 5-FU, CDDP, and VNR were 90%, 92%, and 82%, respectively. The overall survival of the series as a whole was 9.7+ months (range 4-27). Toxicity was generally acceptable. Grades 3 and 4 leukopenia were recorded in 11% and 5% of patients, respectively. Noteworthy was the occurrence of pain at the tumor site after vinorelbine administration in 5 patients. CONCLUSION: The combination regimen of CDDP, 5-FU and vinorelbine is quite active in the treatment of metastatic and/or recurrent SCHNC. This regimen should be tested as initial treatment in previously untreated patients and compared to a standard regimen in recurrent SCHNC.

Interferon alpha treatment of relapsing-remitting multiple sclerosis: long-term study of the correlations between clinical and magnetic resonance imaging results and effects on the immune function.

Interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) are proinflammatory cytokines which may be involved in the pathogenesis of MS. IFN-alpha counteracts many of the proinflammatory actions of IFN-gamma and TNF-alpha. We treated 20 patients with relapsing-remitting (RR) MS with 9 MIU of recombinant IFN-alpha-2a (rIFN-alpha) (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions at serial MRI occurred in 2/12 rIFN-alpha-treated and in 7/8 placebo-treated patients (P < 0.005). Only one new MRI lesion was detected in the rIFN-alpha group, while 27 new or enlarging lesions were detected in placebo group (P < 0.01). Baseline lymphocyte IFN-gamma (19.10 +/- 7.12 U ml-1) and TNF-alpha (18.05 +/- 5.34 pg ml-1) production significantly decreased to 3.03 +/- 0.66 (P < 0.04) (for IFN-gamma) and to 5.78 +/- 0.90 (P < 0.04) (for TNF-alpha) after rIFN-alpha treatment. IFN-gamma and TNF-alpha production was unchanged in the placebo group. rIFN-alpha was tolerated without drop-outs or serious side-effects, but fever, malaise, fatigue (interfering with daily activities in two patients) and leukopenia frequently occurred. High-dose chronic systemic rIFN-alpha might reduce clinical and MRI signs of disease activity in RRMS. The changes in cytokine production suggest that the effect is probably mediated by a down-regulation of proinflammatory cytokine.

Cisplatin plus vp16 as salvage treatment for advanced breast-carcinoma resistant or recurrent after 1st line chemotherapy for metastatic disease.

Forty patients with chemotherapy refractory metastatic breast carcinoma were enrolled in a phase II study of cisplatin 80 mg/m2 on day 1 plus VP16 100 mg/m2 on days 1-3 every 28 days. The overall response rate was 32% (95% CL 17-47%), with 2 patients (5%) showing a CR with a mean duration of 11.3 months, and 11 patients (27%) a PR with a mean duration of 7.8+ months. Seven patients (17%) had stable disease, and 20 patients (50%) progressed despite chemotherapy. One complete response and 4 partial responses were obtained in patients previously untreated with antracyclines. The overall survival was 10.2+ months. The mean survival of responding patients (CR+PR) was 15.5+ months, while that of non responders (NC+PD) was 8.6+ months. A total of 188 cycles were administered (4.7 cycles/patient) and the most frequent toxicities were gastrointestinal and hematological side-effects. The most severe toxicities were intense vomiting and anemia. Grade 3 vomiting was seen in 11 patients (27%), and grade 1-2 anemia in 30% of cases. Severe grade 3 leukopenia was seen in only 12% of cases. Mild renal toxicity was recorded only in 2 cases, while alopecia was observed in almost all patients. In conclusion, although CDDP plus VP16 regimen, may be safely given on an outpatient basis, its routine use as salvage treatment for chemotherapy refractory metastatic breast carcinoma is not recommended. This regimen may, however, be employed as second line chemotherapy in selected cases.

Total body irradiation for myasthenia gravis: a long-term follow-up.

Total body irradiation (TBI) produces prolonged immunosuppression with rare side effects. We studied 12 thymectomized patients affected with chronic generalized severe myasthenia gravis. All patients had been totally or partially refractory to prolonged oral treatment with immunosuppressive drugs, and most had contra-indications for these drugs. Low-dose (1.8- to 2.3-Gy total dose) TBI was administered in single, 0.1-Gy doses, two to three times per week. TBI was well tolerated and was associated with objective clinical improvement in six patients, lasting more than 2 years in five. In addition, TBI produced a long-lasting lymphopenia with a pronounced decrease of T CD4+ lymphocytes; T CD8+ lymphocytes were almost unchanged over the 2 years of the study. CD16+ and CD20+ lymphocytes, after an initial decrease, increased above baseline. TBI was also associated with decreased anti-AChR antibody titer. The decrease of lymphocyte count and of anti-AChR antibody titer was more pronounced in the patients who improved, suggesting that lymphopenia and immunosuppression may have contributed to clinical improvement.