Needle aspiration techniques in preoperative selection of patients with thyroid nodules: a long-term study.

PURPOSE: Long-term evaluation of the combination of two needle aspiration techniques (NAT) (fine-needle aspiration [FNA] and aspiration needle biopsy [ANB]) in performing an efficient preoperative selection of palpable thyroid nodules. PATIENTS AND METHODS: Eight years of extensive use of surgery for the detection of thyroid cancer was compared with 12 years of preoperative selection of by NAT. RESULTS: A total of 1,140 operations were performed from 1972 to 1979, and 35 malignant nodules were discovered (3.1%). Five thousand four hundred three patients were examined by NAT from 1980 to 1992; 483 (9%) underwent surgery and 158 malignant nodules were excised. The number of malignant nodules identified by NAT was 166 (eight were not excised) (3.1% of the total population examined). The principal clinical and pathologic features were similar in both groups. ANB yielded a definite benign diagnosis in 88 patients with inadequate FNA findings, it correctly identified four malignant nodules diagnosed as benign by FNA, it showed a macrofollicular component in 115 nodules diagnosed by FNA as microfollicular nodules, and it significantly changed the predictive value of 79 suspicions FNA diagnoses. CONCLUSION: Introduction of NAT reduced the number of operations for palpable thyroid nodules from 143 to 40 per year and increased from four to 13 the number of malignant nodules excised without any change in the overall incidence of malignant nodules. The combination of ANB to FNA significantly contributed to the high and efficient preoperative patient selection, principally by reducing the number of indeterminate or suspicious, as well as false-negative, preoperative FNA diagnoses.

Natural anticoagulants, aging, and thromboembolism.

The normal aging process alters blood coagulation system in humans; this may be of great concern in the view of the known association of vascular disease with advancing age. The plasma concentration of several coagulation factors, namely fibrinogen, factor VII, factor VIII, factor IX, high molecular-weight kininogen, and prekallikrein, increase in healthy humans, paralleling the physiological aging process. Plasma parameters of clotting activation in vivo, such as prothrombin fragment 1 + 2, fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer, are positively correlated with age. Nevertheless, among centenarians, biochemical signs of marked hypercoagulability are associated with a healthy state. Natural anticoagulants, including antithrombin III, heparin cofactor II, protein C, protein S, and tissue factor pathway inhibitor, can modulate the reactions of blood coagulation system. The occurrence of menopause is accompanied by a significant increase in antithrombin III plasma level; the mean antithrombin III levels in older women exceed levels in male contemporaries. In healthy elderly subjects heparin cofactor II plasma concentrations are lower than in young subjects, independently of gender. Protein C levels raise with age in both sexes, as well as free protein S levels. In women, statistically significant increases in the plasma concentration of the tissue factor pathway inhibitor have been observed, whereas no significant age-related change has been found in men. The fact that many subjects with congenital defects of natural anticoagulants do not undergo thromboembolic events in young age suggests that in healthy individuals a raise in natural anticoagulants can balance the age-related increase of procoagulant factors.

Large-needle aspiration biopsy for the preoperative selection of palpable thyroid nodules diagnosed by fine-needle aspiration as a microfollicular nodule or suspected cancer.

The palpable thyroid nodules with a fine-needle aspiration (FNA) diagnosis of microfollicular nodule or suspected cancer usually are excised; however, most of them are proved benign by postoperative histologic examination. We reviewed the clinical and pathologic data for patients with thyroid nodules with an FNA diagnosis of microfollicular nodule or suspected cancer; nodules also were examined by large-needle aspiration biopsy (LNAB) to assess whether the distinction achieved by LNAB into pure microfollicular or mixed microfollicular-macrofollicular nodules could be used preoperatively to better predict malignancy. One hundred fourteen nodules of this type were excised. The prevalence of cancer was 22% (14/63) among the microfollicular and 4% (2/51) among the microfollicular-macrofollicular nodules at LNAB. These data indicate that histologic examination of the LNAB specimen can be used for preoperative selection of thyroid nodules diagnosed by FNA as a microfollicular nodule or suspected cancer.

Antithrombotic and prothrombotic activities of the vascular endothelium.

Vascular endothelium plays a key role in the control of haemostasis and thrombosis. The main reactions involved in the regulation of platelet reactivity, blood coagulation and fibrinolysis take place at the luminal surface of endothelial cells. Following exposure to certain pathological stimuli, remarkable functional changes of the endothelial cells occur, including downregulation of antithrombotic mechanisms and upregulation of prothrombotic activities. Based on the recent knowledge of vascular endothelial function, a better understanding of the pathogenesis of atherothrombosis is expected.

Plasmatic parameters of fibrin formation and degradation in cancer patients: correlation between fibrinopeptide A and D-dimer.

This investigation was carried out to evaluate fibrin formation and degradation in various types of solid neoplasms by measuring fibrinopeptide A (fpA) in the plasma with a radioimmunoassay and D-dimer (DD) with an enzyme-linked immunosorbent assay in 176 cancer patients; 77 of them showed signs of distant metastasis (M1). FpA and DD were abnormally elevated in 81 and 143 patients respectively. FpA and DD were significantly correlated and unrelated to plasma fibrinogen. Both fpA and DD levels were more elevated in M1 than M0 patients. Coumarin anticoagulants, administered to 32 patients of our series with the aim of preventing cancer growth and dissemination, caused a significant decrease both in fpA and DD levels. Our data provide evidence of increased in vivo fibrin formation and degradation in solid neoplasms: oral anticoagulants can modulate cancer-related hypercoagulation.

Modulation of beta2 integrin phenotype, adhesion, chemotaxis, and oxidative burst of neutrophils by cyclosporine.

Cyclosporine (CsA) is an immunosuppressive drug widely used to prevent allograft rejection, but its action on neutrophil function is not well known. Neutrophils play an important role in tissue damage during allograft rejection; chemotactic recruitment, adhesion to endothelial cells and oxidative burst of neutrophils are early events during allograft rejection. The aim of this work was to evaluate the effect of CsA on beta2 integrins' surface expression, adhesion to human umbilical endothelial cells (HUVECs), chemotaxis and oxidative burst by neutrophils. For any neutrophil function studied, data obtained from activated neutrophils exposed to CsA were compared with those derived from untreated controls. Results show that CsA does not block neutrophil chemotaxis and does not reduce surface expression of CD11 complex and HUVECs' adhesion at all concentrations tested (15, 100 and 500 ng/mL) and at incubation times of 1, 2 and 4 h as compared to controls. On the other hand, the drug affects significantly the CD18 phenotype after two hours of treatment at the maximum concentration (500 ng/mL) (P < 0.05; ANOVA) and the oxidative burst after four hours (P < 0.01; ANOVA). This study provides evidence that in addition to the well-known CsA effects on lymphocyte functions, the drug affects some neutrophil functions with dose- and time-dependent modalities.

The management of idiopathic thrombotic microangiopathy. Changing trends.

Thrombotic microangiopathy, including the two related syndromes thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, is a rare and severe multisystem disorder, due to widespread deposition of intravascular microthrombi consisting mainly of platelets, with subsequent consumption thrombocytopenia, microangiopathic hemolytic anemia, renal abnormalities, and neurologic disturbances. The epidemic, verotoxin-induced hemolytic-uremic syndrome, typically associated with prodromal diarrhea, mainly affects young children in small outbreaks. By contrast, idiopathic thrombotic microangiopathy generally affects adults in a sporadic form; it has a more devastating course and a less favourable outcome. Over 90% of the reported cases in the adult, when untreated, have progressed to death within three months of diagnosis. Since the introduction of plasma exchange, a dramatic change in the prognosis of the disease has taken place, although the mortality rate still remains considerable. Indeed, improved survival is the most striking feature of adult thrombotic microangiopathy compared to some decades ago. In the present article we will focus on the evolving concepts able to exert a considerable impact in the management of the adult idiopathic form of thrombotic microangiopathy.

Thrombotic and hemorrhagic complications in chronic myeloproliferative disorders.

Bleeding and thrombosis are major causes of morbidity and mortality in patients with chronic myeloproliferative disorders. We retrospectively evaluated 101 consecutive patients affected by primary thrombocytosis (46 male, 55 female, aged 18-84 years; mean +/- SD 61 +/- 15) followed for a period ranging from 6 months up to 10 years (median 5 years) at our hematological unit. At the time of diagnosis 48 patients were asymptomatic; 26 had clinical evidence of atherothrombosis (cerebral ischemic attacks, ischemic heart disease, peripheral occlusive arterial disease), ten had venous thrombosis, four experienced major hemorrhages, 23 presented microvascular ischemic manifestations namely erythromelalgia, paresthesias, acrocyanosis and dizziness. At presentation 51.2% of the patients had elevated serum lactic dehydrogenase, 34.5% hyperuricemia, and 23.4% serum creatinine > 1.2 mg/dL. Color Doppler ultrasound provided evidence of vascular stenosis or medium-intimal hyperplasia of epiaortic vessels in 48.9% of patients studied, and similar alterations of lower limb arteries in 23.8% of cases. Therapy modality included an antiplatelet agent (picotamide 300 mg/bid); a cytoreductive agent (busulphan, hydroxyurea, pipobroman or melphalan) was used when platelet count was > 800000/microL. Symptoms due to microvascular ischemia promptly regressed after picotamide and cytoreductive therapy. During follow-up. nine patients suffered from atherothrombotic events (transient ischemic attacks, ischemic stroke, unstable angina pectoris) and five developed deep vein thrombosis or superficial thrombophlebitis. Five patients experienced major hemorrhages (two melena, two hematuria, one perioperative bleeding); the two gastrointestinal hemorrhages occurred in patients self-medicated with non steroidal anti-inflammatory drugs, and the two episodes of hematuria occurred on oral anticoagulant therapy and aspirin respectively. No major bleeding occurred in patients on continuative therapy with picotamide, even in the presence of upper digestive tract disorders. Seven patients died: mortality resulted from one sudden coronary death, three solid neoplasia, one blast crisis, one anile, and one massive hemorrhage due to abdominal aortic prosthesis tearing. Our study suggests that a long-term antithrombotic prophylaxis with picotamide may be of benefit in patients affected by primary thrombocytosis; a controlled clinical trial is warranted to assess whether picotamide can ameliorate the natural history of the disease.

Expression of tissue-type plasminogen activator, plasminogen activator inhibitor and von Willebrand factor in the supernatant of endothelial cell cultures in response to the seeding of adenocarcinoma cell line HRT-18.

Plasminogen activator inhibitor (PAI-1), tissue type plasminogen activator (tPA) and von Willebrand factor (vWF) concentrations were measured by ELISA in the supernatant of the following cultures: endothelial cells from human umbilical vein (HUVEC); human colon cancer cells (HRT-18); and co-culture cells of HUVEC + HRT-18. No measurable amount of the three substances was found in the supernatant of HRT-18 cell culture. Compared to the value in the HUVEC supernatant, in the UVEC/HRT-18 co-cultures, tPA concentration was significantly lower (P = 0.0047), PAI-1 significantly higher (P = 0.026) and vWF also significantly higher (P = 0.0048). These data indicate that HRT-18 tumor cells do not produce tPA, PAI-1 and vWF; however, these tumor cells induce endothelial cells to change the production of these substances. As a consequence, the interaction between tumor and endothelial cells in vivo may lead to depression of fibrinolysis and enhancement of platelet adhesion.

A multistep therapy with subcutaneous low dose recombinant interleukin-2, 5-fluorouracil and leucovorin prolongs the response of metastatic colorectal cancer patients: a pilot study.

Data from 12 metastatic colorectal cancer patients who were submitted to a pilot study with a multistep subcutaneous (sc) low dose recombinant interleukin-2 (rIL-2), 5-fluorouracil (5-FU) and leucovorin (LV) administration were compared with those from 13 historical controls who were comparable for the major prognostic indices. All 12 patients in the pilot study were subjected initially to six to eight courses of 5-FU-LV by endovenous (ev) bolus consistent with the Machover schedule alternating with 6 weeks of rIL-2 cycles. At the progression of metastatic disease, the patients were given 500 mg/m2 per day of 5-FU by continuous infusion (ci) for 5 days every 4 weeks and in case of further progression, 2,600 mg/m2 of 5-FU by 24-h ci once a week for 6 weeks. The control patients were treated with 5-FU-LV by the Machover schedule until progression and then observed. As yet, two patients in the pilot study and three control patients are currently alive. In the pilot study, the patients' response rate (CR + PR) and overall response rate (CR + PR + SD) were much higher than in the controls (50 vs 23% and 92 vs 54%, respectively). Time duration of response and survival from primary surgery were more prolonged in the pilot study than in the historical control, although not significantly (10.5 vs 6 and 41.5 vs 29 months, respectively). Time from starting therapy to progression and survival from relapse were significantly in favour of the pilot study (11.5 vs 4 and 31 vs 13.5 months; P < 0.01 and P < 0.05 unpaired t-test, respectively). Low dose s.c. rIL-2 cycles were well tolerated and no interruption occurred. In the pilot study sporadic grade 3 toxicity (diarrhoea or leucopenia) was responsible for the reduction of 5-FU doses to 80% of the previous infusion, but no treatment was postponed. In conclusion, these preliminary data suggest the opportunity to initiate large prospective randomized trials using a multistep therapy with rIL-2, 5-FU ci at conventional and at high dose in metastatic colorectal cancer.

The combination of aspiration needle biopsy with fine needle aspiration in the preoperative evaluation of breast tumors.

During a period of 10 years, 2906 women (mostly asymptomatic) were referred to us for physical breast examination. Fine needle aspiration (FNA) was used to examine a nodule or a breast thickening in 860 of these patients. One hundred and ten of these patients also underwent a large needle biopsy (LNB) to add a pre-operative histological evaluation. LNB was performed with 18-20 gauge needles, without cutting the skin and without adding any significant pain or discomfort to that caused by FNA (aspiration needle biopsy, ANB). Diagnostic sensitivity for cancer was 89% for FNA and 100% for ANB. ANB allowed us to correctly identify two cancers with post-operative stage T1N0M-0, which were diagnosed pre-operatively as benign by FNA. The combination of the two needle aspiration techniques (FNA and ANB) allowed us to diagnose 51 of all the 54 cancers (95%). The predictive value of a diagnosis of definite malignancy was 100% for either FNA or ANB. The predictive value of a diagnosis of suspected malignancy showed a predictive value of 72% for FNA and 70% for ANB. Three benign nodules with pre-operative ANB findings of suspected cancer were correctly diagnosed by FNA. Of the 12 cancers with inadequate ANB findings, 11 were correctly diagnosed by FNA. Sixteen of the cancers correctly identified by ANB showed a post-operative size of 2 cm or less (ten cases) or no metastatic axillary lymph-nodes (nine cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Von Willebrand's factor mediates the adherence of human tumoral cells to human endothelial cells and ticlopidine interferes with this effect.

The aim of this study was to explore whether von Willebrand's factor (vWF) plays a role in the adhesion of human colon tumor cells to human endothelial cells in our coculture system. Cell colony density was evaluated basally (endothelial plus colon tumor cells) and following the addition of: purified vWF, vWF plus vWF-blocking antibodies, antibodies against various integrins and adhesion molecules (alpha2 b integrin, beta1 integrin, beta3 integrin, intercellular adhesion molecule-I, intercellular adhesion molecule-II, vitronectin receptor CD61 CD51, laminin alpha6/beta4 receptor), and various drugs inhibiting the hemostatic system (ticlopidine, heparin, acetyl salicylic acid [ASA], defibrotide, indobuphen, dipyridamole, sulfinpyrazone). Furthermore, vWF concentration was measured in the supernatant fluid of the coculture system basally and following the addition of the above-listed drugs. Cell colony density (as measured by light absorption) increased by 33% following the addition of vWF and returned to a value similar to the basal level with antibodies against vWF, while it did not change significantly following the addition of antibodies against the other integrins or adhesion molecules tested. The same parameter was reduced by 35% following the addition of ticlopidine, while it showed a smaller or no change with the other drugs tested. Similarly, vWF concentration in the cell coculture supernatant showed the greatest reduction (from 0.22 to 0.11 mg/mL) following the addition of ticlopidine. These data suggest that vWF mediates the adherence of human tumor cells to human endothelial cells and that ticlopidine interferes with this effect.

Cell-mediated immunity in breast cancer patients.

In clinical practice, reports have been made on immunosuppression after surgical excision of primary tumor or at relapse. However, the relationship between undefined or overt metastases and the host immune system has not been sufficiently examined over a prolonged period. These aspects were investigated in 160 breast cancer patients followed up post-operatively with serial controls over a long period. One hundred and thirty-four cases (91 node negative, (N-), 43 node positive (N+)) were disease-free and 26 relapsed. In all patients, serum T cell populations, serum B lymphocytes and skin reaction of delayed hypersensitivity (SRDH) were serially determined for 39 +/- 12 months (m +/- SD). The reference values for these parameters were assessed as follows: T populations were evaluated in 24 healthy donors and SRDH in 95 healthy females. In non-relapsed patients, constant CD8+ T cell decrease and T4/T8 ratio increase were observed; the T4/T8 ratio was significantly higher (ranging from P < 0.05 - P < 0.001) than in the control group. The mean values of NK cells and B lymphocytes, the former parameter being highly significant (P < 0.001), were higher than in controls. In the 26 metastatic patients, the T4/T8 ratio from 20 months before to 30 months after the first sign of relapse decreased from 3.2 to about 1 (r = -0.256, P < 0.05) and from 30 to 92 months after relapse progressively increased to 2. Similarly, in the former subinterval a progressive decrease in the number of positive antigens and score was found (from 2.4 to 0 and from 10 to zero respectively). A significant inverse correlation between these two parameters and observation time occurred (P < 0.01 and P < 0.001 respectively). From 30 to 86 months after relapse, a progressive increase in the number of positive antigens and scores up to 2 and 12 were observed. A significant direct correlation (P < 0.05) was noted. In conclusion, these data indicate significant changes in T populations during the disease-free interval in breast cancer patients. The decrease in circulating CD8+ T cells is compatible with the hypothesis of CD8+ T cell localization at the site of the micrometastases. The increase in circulating B lymphocytes and NK cells suggests activation of aspecific humoral immunity and NK function. In addition, they show that progressive deficiency in cell-mediated immunity appears many months before and that recovery continues for a long time after overt metastatic disease.

Immunological and side effects of low sc recombinant interleukin-2 dose in addition to conventional treatment in relapsed breast and colorectal cancer patients.

Thirteen relapsed cancer patients, four of them operated for colorectal and the nine remaining for breast cancer, were cyclically given low subcutaneous (sc) recombinant interleukin-2 (rIL-2) doses in addition to chemo- or hormone therapy. Cycle intervals were 2 or 6 weeks in length, and the number of cycles ranged from one to 14 and from one to six respectively. Tolerance assessed by clinical and laboratory data, eosinophils, lymphocytes (total number), T subpopulations, B lymphocytes and NK cells were the evaluated parameters. One (7.6%) of the 13 studied patients interrupted the first low dose sc rIL-2 cycle due to a hypersensitive reaction. This case showed relapse from breast cancer. During further cycles, three patients (25%), one operated on for colorectal and two others for breast cancer of the 12 remaining cases who completed all rIL-2 cycles showed an increase in glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-gt, and creatininemia without any clinical symptoms. A slight influenza-like syndrome and 10-20 mmHg decrease in blood pressure sporadically occurred in all patients under rIL-2 therapy. In both cancer types, a significant (P < 0.05 - P < 0.001) increase in lymphocytes, eosinophils. T4 and T3 subpopulations but not in T8 subpopulations and NK cells occurred at the end of the rIL-2 cycles. In 11 of the 13 patients responsive to conventional therapy, a highly significant increase (P < 0.001) in all parameters apart from B lymphocytes and T4/T8 ratio was observed, while in three cases which were no longer responsive and in another case which had never been responsive to conventional therapy, a slightly significant increase in eosinophils only occurred (P < 0.05). Three colorectal cancer patients showed a partial response and the last a complete response to conventional therapy. In these four patients, time to progression during rIL-2 cycles ranged from 2.5-5 months and the duration of response ranged from 8-19 months. In seven of the eight breast cancer patients who completed all rIL-2 cycles, the response ranged from 3-51+ months and in the last case, which was not responsive to conventional therapy, the disease progressed in spite of the addition of rIL-2. These data suggest that: a) rIL-2 is likely to constitute a well-tolerated and suitable home therapy even when cyclically given for a prolonged period; b) following rIL-2 administration, eosinophils and lymphocytes increase in addition to the T subpopulations.

Iloprost in the treatment of thrombotic microangiopathy: report of thirteen cases.

Defective prostacyclin bioavailability seems to play a role in the pathogenesis of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Eight consecutive patients with a proven diagnosis of thrombotic microangiopathy were treated by Iloprost, a recently developed stable prostacyclin analogue; during follow-up, three of them relapsed and received further treatment. To our knowledge, this is the first report on a wide series of patients who received Iloprost for thrombotic microangiopathy. Soon after diagnosis, Iloprost was given by continuous intravenous infusion at a rate of 1.5-2 ng/kg/minute over 16-18 h/day for several days (mean 12 days; range 6-24) until the platelet count steadily increased. In addition, plasma exchange with fresh frozen plasma (average volume exchange 20-40 mL/kg for each session) was performed in 11 out of the 13 cases. No other antiplatelet agent was given. In all 13 cases, Iloprost administration coincided with achievement of remission. At present, all the patients are still maintaining remission. Our results indicate a useful role for Iloprost in the management of thrombotic microangiopathy.

Plasmatic parameters of coagulation activation in thrombotic microangiopathy.

Coagulation activation and fibrinolysis parameters were studied in eleven cases of thrombotic microangiopathy concerning eight adult patients. In addition to routine coagulation tests, antithrombin III, von Willebrand factor (vWF), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), D-dimer (DD), and plasminogen activator inhibitor type 1 (PAI-1) were measured in the plasma at the time of diagnosis and as soon as remission was achieved after therapy with plasma exchange and Iloprost. In the acute phase all patients showed normal aPTT, normal or slightly prolonged prothrombin time, normal or enhanced plasma levels of fibrinogen and antithrombin III, at variance with results in patients affected by disseminated intravascular coagulation. Mean F1+2, TAT, DD, vWF and PAI-1 were elevated in the acute phase, but decreased significantly in the early phase of remission. Our data provide evidence of increased thrombin generation rate which takes place in the acute phase of the disease and does not result in consumption coagulopathy, due to appropriate inhibition by antithrombin III; blood coagulation activation promptly decreased as soon as remission was achieved. Cross-linked fibrin deposition together with PAI-1 may consolidate the platelet plug, eventually resulting in microvascular occlusion and ischemia.

Detection of minimal but significant amount of von Willebrand factor in human omentum mesothelial cell cultures.

The presence of von Willebrand factor (vWF) in human mesothelial cells is a controversial issue. The aim of this paper was to investigate the presence of vWF in human mesothelial cell cultures by means of multiple specific techniques and to compare the amount of vWF to that in endothelial cell cultures. Morphological evidence that vWF is present in the cell cytoplasm in human omentum mesothelial cells (HOMC) has been obtained by vWF staining by means of anti-vWF antibodies and immunofluorescence. The vWF concentration value (measured by ELISA) was 0.02 ng/mL in the supernatant of HOMC (160,000 ng/mL cells/mL after 12-48 hours) and between 0.08-0.12 ng/mL in the supernatant of endothelial cell cultures (160,000 cells/mL). Ethidium-bromide staining of PCR products recorded the typical vWF signal both in the endothelial and in the mesothelial cell cultures, although it was noticeably more intense in the endothelial cell culture. These data show that minimal but significant amounts of vWF are present in human mesothelial cell cultures.

Anti-D treatment for chronic immune thrombocytopenic purpura: clinical and laboratory aspects.

We used low-dose anti-D immunoglobulins for home treatment of Rh+ adult patients with chronic immune thrombocytopenic purpura (ITP). After informed consent, 15 unselected outpatients (ten males and five females, aged 22 to 72), affected by chronic ITP with negative HIV test, were given intramuscular injection of 900-1500 micrograms of anti-Rh0 (D) IgG over 3 days every month for 2 or 3 consecutive months. Platelet count (mean +/- SD) significantly increased from basal value of 17,000 +/- 9,000/microL to 72,000 +/- 55,000/microL at the end of treatment. Eight patients achieved a rise in platelet count above 50,000/microL (five above 100,000/microL) and two of them maintained the increase longer than 6 months without further anti-D administration. Three patients responsive to the first cycle responded to further treatment with substantially identical results. Seven patients had no response. Four of them had not responded to previous glucocorticoid and intravenous IgG therapy. Direct antiglobulin test became strongly positive in all patients and mean serum haptoglobin decreased from a basal value of 118 +/- 59 to 61 +/- 43 mg/dL; nevertheless no clinically overt hemolysis was observed in any patient, there was no rise of serum indirect bilirubin and hemoglobin level was unchanged (mean +/- SD basal level 13.6 +/- 2.2 g/dL; after anti-D 13.9 +/- 1.2 g/dL). No hematoma developed at the injection site, and no other side effects occurred. Our results show that anti-D therapy is effective in the majority of patients well tolerated, and feasible as home treatment: thus it can be recommended as a cheap and safe alternative treatment in ITP Rh+ patients.

Large needle aspiration biopsy for reducing the rate of inadequate cytology on fine needle aspiration specimens from palpable thyroid nodules.

From 1980 to 1996, 1,907 consecutive euthyroid subjects with palpable thyroid nodules were examined by fine needle aspiration (FNA) cytology plus large needle aspiration biopsy (LNAB) histology. There were 1,630 (85%) women and 277 (14.5%) men aged from 17 to 80 years. A single nodule was palpated in 1,419 subjects (74.4%) while 488 (25.6%) showed multiple nodules. The nodule size ranged between 1 and 7.5 cm. The number of inadequate specimens at the first examination, FNA cytology of LNAB histology, were 261 (13%) or 398 (20.8%), respectively. LNAB performed on the 261 nodules with nondiagnostic cytology showed findings which were adequate for diagnosis in 130 (49.8%) and inadequate in 131 (50.2%). Among the 261 patients with inadequate initial cytological findings 61 were subjected to repeated FNA and 36 repeated LNAB. More than 60% of the nodules on which FNA was repeated achieved a cytological diagnosis; more than 80% of the nodules reinvestigated by LNAB were finally diagnosed by histology. The mean nodule size was larger in the group with inadequate result than in that with adequate FNA or LNAB result. Among the 261 patients with inadequate cytological finding at the first FNA 28 were operated on; 20 were in the group with adequate LNAB histological findings and eight in the group with an inadequate LNAB. Two papillary cancers, one per group, were found at postoperative histology. However, one was diagnosed by LNAB and one at the second FNA. The remaining 26 nodules were all found to be benign postoperatively. This study shows that the addition of LNAB to FNA leads to a histological diagnosis in 50% of the palpable thyroid nodules with inadequate cytology at the first FNA and that LNAB can be used even for those nodules which remain uncharacterized after repeat FNA.

Aspiration needle biopsy refines preoperative diagnosis of thyroid nodules defined at fine needle aspiration as microfollicular nodule.

The aim of this paper was to verify the hypothesis that large needle biopsy performed preoperatively can refine preoperative fine needle aspiration (FNA) cytological diagnoses of microfollicular nodules. Since 1980 we have been using FNA and aspiration needle biopsy (ANB) (18 or 16 gauge needles) to select for surgery all euthyroid patients with palpable thyroid nodules referred to our department. From 1980 to 1994, 6,124 patients (12% male, 88% female) with thyroid nodules (71% single, 29% multiple) were examined by FNA; 29% of these patients were also examined preoperatively by ANB histology. Of all the nodule patients examined, 371 received a preoperative FNA diagnosis of microfollicular nodule. Two hundred and fifty-four of these nodules (68%) were also examined preoperatively by ANB. Unsatisfactory ANB specimens constituted 17% of cases; pure microfollicular structure was confirmed by ANB in 36% of the nodules; ANB showed the remaining 47% to contain a macrofollicular component, thus suggesting a benign hyperplastic lesion. Twelve nodules which were found to be microfollicular at FNA cytology and micro-macrofollicular at ANB were excised and were subsequently determined as benign at definitive postoperative histology. These data indicate the utility of ANB in refining the preoperative FNA diagnosis of microfollicular nodule and in preoperatively identifying benign hyperplastic mixed micro-macrofollicular lesions which can be followed by observation.