Clinical impact of the new SIAPEC-IAP classification on the indeterminate category of thyroid nodules.

BACKGROUND: The increasing frequency in the diagnosis of thyroid nodules has raised a growing interest in the search for new diagnostic tools to better select patients deserving surgery. In 2014, the major Italian Societies involved in the field drafted a new cytological classification, to better stratify pre-surgical risk of thyroid cancer, especially for the indeterminate category, split into TIR3A and TIR3B subclasses, associated to different therapeutic decisions. MATERIALS AND METHODS: This retrospective cross-sectional survey analyzed thyroid fine-needle aspiration biopsy performed at our outpatient clinic before and after the introduction of the new SIAPEC-IAP consensus in May 2014. RESULTS: 8956 thyroid nodules were included in the analysis: 5692 were evaluated according to the old classification and 3264 according to the new one. The new criteria caused the overall prevalence of TIR3 to increase from 6.1 to 20.1%. Of those, 10.7 and 9.4% were included in the TIR3A and TIR3B subgroups, respectively. Each of the 213 TIR3B nodules underwent surgery and 86 (40.4%) were diagnosed as thyroid cancer, while among the 349 TIR3A nodules, only 15 of the 60 that underwent surgery were found to be thyroid cancer. CONCLUSIONS: This analysis shows that the new SIAPEC-IAC criteria significantly increased the proportion of the overall TIR3 diagnosis. The division of TIR3 nodules into two subgroups (A and B) allowed a better evaluation of the oncologic risk and a better selection of patients to be referred to surgery.

Characterization of a novel HLA-B allele (HLA-B*18:108) by intron-exon sequencing of the HLA-B locus.

HLA-B*18:108 has two nucleotide changes from B*18:01:01:02 at nt 430 where A → G and nt 431 where G → A.

Comparison of dosimetry with magnetic resonance and computed tomography imaging delineation of surgical bed volume in breast cancer irradiation.

Background: Postoperative radiotherapy after conservative surgery for patients with breast cancer usually includes focal over-irradiation (boost) to the surgical bed (SB). Irradiation planning using computed tomography (CT) is difficult in many cases because of insufficient intrinsic soft tissue contrast. To ensure appropriate radiation to the tumor, large boost volumes are delineated, resulting in a higher dose to the normal tissue. Magnetic resonance imaging (MRI) provides superior soft tissue contrast than CT and can better differentiate between normal tissue and the SB. However, for SB delineation CT images alone remain the pathway followed in patients undergoing breast irradiation. This study aimed to evaluate the potential advantages in boost dosimetry by using MRI and CT as pre-treatment imaging. Methods: Eighteen boost volumes were drawn on CT and MRI and elastically co-registered using commercial image registration software. The radiotherapy treatment plan was optimized using the CT volumes as the baseline. The dose distributions of the target volumes on CT and MRI were compared using dose-volume histogram cutoff points. Results: The radiation volumes to the SB varied considerably between CT and MRI (conformity index between 0.24 and 0.67). The differences between the MRI and CT boost doses in terms of the volume receiving 98% of the prescribed dose (V98%) varied between 10% and 30%. Smaller differences in the V98% were observed when the boost volumes were delineated using MRI. Conclusion: Using MRI to delineate the volume of the SB may increase the accuracy of boost dosimetry.

A simple ultrasound score for the identification of candidates to fine needle aspiration of thyroid nodules.

BACKGROUND: Cytological examination of fine needle aspirates (FNA) is the standard procedure for discriminating potentially malignant thyroid nodules to be referred to surgery. In a fraction of cases, ultrasound (US) examination could provide information theoretically sufficient to avoid FNA, when typical US features suggesting malignancies are lacking. AIM: The aim of this study was to construct a simple US score predicting malignant nodules so as to reduce the number of unnecessary FNA. SUBJECTS AND METHODS: In a series of 1632 consecutive patients undergoing US-guided FNA (1812 nodules), echostructure, echogenicity, margins, halo, microcalcification, and vascularization were assessed. RESULTS: At multivariate analysis, the following parameters showed a strong predictive value for positive cytology (Thy 4 and Thy 5, suspicious and diagnostic for malignancy, respectively, according to the Thyroid British Association): solid echostructure, irregular margins and hypoechogenicity [adjusted odd ratio (OR) 5.13 (1.58-16.66), 3.03 (1.70-5.39), 2.05 (1.17-3.57), respectively]. A 10-point Thyroid Risk Ultrasound Score (TRUS) was constructed on the basis of the adjusted OR. A TRUS≥6 identified malignant nodules with sensitivity and specificity of 73% and 65%, respectively. Among the patients with follicular lesions (Thy 3) and final diagnosis of carcinoma, about 65% had a TRUS≥6.0. CONCLUSIONS: The sensitivity of TRUS, although higher than that of other scores, could still be insufficient for the identification of patients who could avoid FNA in routine clinical practice, whereas its predictive value for Thy 3 lesions deserves further investigations.

A Literature Systematic Review with Meta-Analysis of Symptoms Prevalence in Covid-19: the Relevance of Olfactory Symptoms in Infection Not Requiring Hospitalization.

PURPOSE OF REVIEW: To investigate the association between the olfactory dysfunction and the more typical symptoms (fever, cough, dyspnoea) within the Sars-CoV-2 infection (COVID-19) in hospitalized and non-hospitalized patients. RECENT FINDINGS: PubMed, Scopus and Web of Science databases were reviewed from May 5, 2020, to June 1, 2020. Inclusion criteria included English, French, German, Spanish or Italian language studies containing original data related to COVID19, anosmia, fever, cough, and dyspnoea, in both hospital and non-hospital settings. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools. A third author arbitrated full-text disagreements. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 of 135 studies fulfilled eligibility. Anosmia was estimated less prevalent than fever and cough (respectively rate difference = - 0.316, 95% CI: - 0.574 to - 0.058, Z = - 2.404, p < 0.016, k = 11 and rate difference = - 0.249, 95% CI: - 0.402 to - 0.096, Z = - 3.185, p < 0.001, k = 11); the analysis between anosmia and dyspnoea was not significant (rate difference = - 0.008, 95% CI: - 0.166 to 0.150, Z = - 0.099, p < 0.921, k = 8). The typical symptoms were significantly more frequent than anosmia in hospitalized more critical patients than in non-hospitalized ones (respectively [Q(1) = 50.638 p < 0.000, Q(1) = 52.520 p < 0.000, Q(1) = 100.734 p < 0.000). SUMMARY: Patient with new onset olfactory dysfunction should be investigated for COVID-19. Anosmia is more frequent in non-hospitalized COVID-19 patients than in hospitalized ones.

Identification of the new HLA-DPB1 allele, DPB1*647:01, in an Italian patient with leukemia.

A novel HLA-DPB1 allele, named HLA-DPB1*647:01, identified in a leukemia patient.

Characterization of a novel HLA-C allele, HLA-C*04:288, in an Italian patient.

The novel HLA-C*04:288 differs from HLA-C*04:01:01:06 by a single nucleotide substitution in exon 2.

Characterization of a novel HLA-B*18 variant allele, HLA-B*18:122, by genome sequencing.

The HLA-B*18:122 allele showed four nucleotide differences from HLA-B*18:01:01:01.

Identification of a new HLA-A*24 allele, A*24:309, in an Italian bone marrow donor.

A novel class I human leukocyte antigen allele HLA-A*24:309 is described.

Evaluation of therapeutic modalities in the control of Hodgkin's disease.

The results achieved in three different studies carried out on patients affected by Hodgkin's disease are discussed. In study No. 1, 58 patients with pathological Stage I-II were treated with only a "Mantle" field irradiation. The complete remission (CR) rate was 98% with an actuarial overall survival of 90%, and a median of follow-up of 80 months. Thirty-one percent of patients relapsed. In study No. 2, 42 patients were randomly allocated to receive only MOPP chemotherapy versus extended field irradiation; CR rate was 68 and 95%, respectively (p less than 0.05). The overall survival rate was 100% in the radiotherapy group and 82% in the MOPP group. No relapses have been observed in patients treated with MOPP. In study No. 3, 218 patients affected by advanced Stage HD were randomly treated with 6 cycles of MOPP chemotherapy versus 6 cycles of ABVD chemotherapy. In the MOPP group the CR rate, the relapse-free survival rate (RFS), and overall survival (OS) rates at 60 months were 77, 68, and 76% respectively, whereas, in the ABVD group the CR, the RFS, and OS rates at 60 months were 75, 77 and 80% respectively, (p less than 0.05). These data and statistical comparisons are analyzed.

Fractionated total body irradiation in allogeneic bone marrow transplantation in leukemia patients: analysis of prognostic factors and results in 136 patients.

BACKGROUND AND PURPOSE: The results of a single-institution series of patients with chronic and acute leukemias are analyzed with regard to literature-reported predictor variables. MATERIALS AND METHODS: Between 1985 and 1994, 136 patients, 82 patients with chronic myeloid leukemia (CML) and 54 with acute leukemia (AL), received a uniform preparatory regimen of fractionated total body irradiation (TBI; 12 Gy in 3 days) plus different chemotherapy regimens before bone marrow transplantation. Eighty-six patients were considered to be in early phase of disease (CML in chronic phase or AL in first complete remission) and 50 in advanced phase (all those beyond first remission or first chronic phase). Ninety-five patients received unmanipulated allogeneic BM, and 41 T-lymphocyte-depleted BM. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) of the whole series were 43% and 31%, and median survival was 43 and 10 months, respectively. A Cox proportional hazard model identified variables related to overall and disease-free survival. For OS, graft versus host disease (GVHD) was the first independent variable (P < 0.0001), followed by age (P < 0.001), T-depletion (P < 0.01), disease status (P < 0.05) and type of leukemia (P < 0.05). With regard to DFS, only T-depletion (P < 0.0001), disease status (P < 0.01) and GVHD (P < 0.01) resulted predictor factors. Early complications after BMT were reported in 59 patients, TBI-induced delayed toxicity in 9 patients, and 16 patients suffered late complications. CONCLUSIONS: Our results confirm the curability of early phase leukemias with standard fractionated TBI-induced Allogeneic bone marrow transplantation (ABMT). With an homogeneous fractionated TBI schedule as employed in our series, T-cell depletion negatively affected the outcome.

Local hyperthermia and radiation therapy in the treatment of superficially located lymphomas and recurrent Hodgkin's disease.

The combination of radiation therapy CRT) and hyperthermia (HT) has proved to be an effective treatment of a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Some studies have been reported with the use of this combined approach in the management of cutaneous lymphomas or recurrent previously irradiated sites of Hodgkin's disease (HD). We report a small series of five patients with six located sites of recurrent HD, and four patients with six superficially located sites of non Hodgkin's lymphomas (NHL), all of them being treated with combined HT and RT at our institution. Local control was obtained in each of combined treatment fields, and all patients are alive after a median follow-up of 24 months. All the patients tolerated the HT treatments well, and in all cases average intratumoral temperatures were >42 degrees C, with 8 out of 12 sites achieving the goal of average temperatures >42.5 degrees C. Two patients, one with recurrent HD and one with NHL, are free of disease after 20 and 21 months from the end of combined therapy. Our results thus seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also in the management of selected, heavily pretreated patients with superficially located recurrences of HD.

Multiple interferences on catecholamine metabolism by tetrahydroisoquinolines (TIQs).

TIQs are thought to be formed by condensation between dopamine and certain metabolites of ethanol, organic solvents and anesthetic gases. Described here are experiments aimed at evaluating TIQs interference with catecholamine synthesis. Rat adrenal pheochromocytoma (PC12) cell lysates were exposed to benzyl-TIQ and phenyl-TIQ. The activities of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) were measured by HPLC-based methods following exposure to variable concentrations of TIQs. The effects of TIQs on DBH activity were also assessed in human serum. Dixon plot analyses revealed that TIQs act on TH as competitive inhibitors with different affinity. Ki for benzyl- and phenyl-TIQ were 5 and 3 microM respectively. DBH activity in serum exposed to benzyl- and phenyl-TIQ ranging from 0.2 to 20 microM rose respectively by 12.5% to 58% for benzyl- and by 7.8% to 26% for phenyl-TIQ. Such TIQs interferences with catecholamine metabolism seem to account for dopamine (DA) depletion observed in parallel in vitro experiments on PC12 cells. The dose-dependent inhibition of TH and the increased activity of DBH together with the relatively low effective doses of TIQs suggest this mechanism as a possible explanation of the selective toxicity of styrene and other solvents to dopaminergic systems observed in rabbits following experimental exposure and suspected to occur in occupationally-exposed workers.

Radiation therapy and chemotherapy in the treatment of head and neck extranodal non-Hodgkin's lymphoma in early stage with a high grade of malignancy.

BACKGROUND: Optimal management of patients with localized head and neck extranodal lymphoma remains controversial, both because of the lack of randomized studies and because of the heterogenous grouping of most reported series. MATERIALS AND METHODS: Patients treated at our institution between 1974 and 1993 for extranodal head and neck lymphoma were retrospectively analyzed and classified. The therapy and outcome of 92 patients classified as having an intermediate (42) and high (50) level of malignancy according to the Working formulation and in stage I (39) or II (53) of the Ann Arbor Staging System were considered. Fifty-three patients (57.6%) received chemotherapy alone, and 39 (42.4%) combined radiochemotherapy. RESULTS: The different treatment schedules allowed these patients to achieve global actuarial 5-year overall, event-free, and relapse-free survival rates of 81.2%, 78.1% and 89.3%, respectively. The patients that received combined modality treatment reported actuarial 10-year event-free and relapse-free survival rates of 65.3% and 90.7%, respectively, with a suggestion of decreased treatment-related morbidity compared to patients treated with chemotherapy. CONCLUSIONS: Our results underscore the important treatment role of combined radiochemotherapy for early stage intermediate and high grade lymphomas.

Micronucleated lymphocytes in people occupationally exposed to potential environmental contaminants: the age effect.

This work is part of a research project on 2 groups of tannery workers (i.e., workers employed in the tanning process and those employed in the finishing department), and 2 control groups consisting of individuals paired with each exposed person according to sex, age and smoking habit. The whole study included the evaluation of micronuclei as well as of chromosomal aberrations and sister-chromatid exchanges in peripheral blood lymphocytes. Data on micronucleus analysis in both controls and exposed persons are shown in this paper. There was no statistically significant difference between MN frequencies in the 2 groups of exposed and controls, nor any positive correlation with smoking habit. The effect of age on basal frequency of micronucleated cells clearly emerges in the present study: both controls and exposed show an increase in MN frequency due to age. This could be correlated with a higher sensitivity to breaks, rearrangements or aneuploidogenic events of circulating lymphocytes in aged people.

Multicentre experience with combined hyperthermia and radiation therapy in the treatment of superficially located non-Hodgkin's lymphomas.

The combination of Radiation Therapy (RT) and Hyperthermia (HT) has proved to be an effective treatment for a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Few studies on the use of HT in the management of lymphomatous diseases have so far obtained interesting results. Eight patients with Non Hodgkin Lymphomas (LNH) - 4 with cutaneous lymphomas and 4 with nodal recurrences after RT-Chemotherapy (CHT) treatment treated in three different Italian institutions with combined RT and HT are here reported. Rt dose ranged from 15 to 40 Gy with different fractionations, on the basis of previously received treatment. Hyperthermia was delivered using 432 or 915 MHz external microwave applicators, according to extension and depth of the lesions and available equipment. All patients tolerated well the HT treatment, and in all cases average intratumoral temperatures were >42 degrees, with 3 out of 10 treated sites achieving the goal of average temperatures >42.5%. One patient, with recurrent NHL, is disease-free after 24 months from completion of combined therapy. Our results seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also as an adjunct to radiotherapy alone in selected patients with superficially located recurrences.

Treatment by splenic irradiation in 22 chronic lymphocytic leukemia patients.

Twenty-two patients with chronic lymphocytic leukemia, score 2 according to Rai et al. (10), who received only a course of splenic irradiation are reviewed. Splenic doses ranged from 420 to 1080 rad. Response to splenic irradiation was rated by evaluating peripheral lymphocytosis, hepatosplenomegaly, adenomegaly and disease-related symptoms. Following splenic irradiation, 8 patients showed a significant reduction in splenomegaly; 7 patients showed a significant reduction in peripheral lymphocytosis (less than 10,000/mm3), which has lasted from 15-42 months without any other treatment. In 14 patients, response to splenic irradiation was partial, and it has successively been necessary to treat 12 patients with chemotherapy. Methods of splenic irradiation, survival, clinical and hematologic behavior are discussed in detail.

Involvement of the bone marrow by non-Hodgkin's lymphomas: incidence, histology and pathologic correlations.

The Lukes and Collins system of classification was applied to 151 cases of non-Hodgkin's lymphoma who had bone marrow biopsies taken immediately after histologic diagnosis. Incidence and histologic pattern of bone marrow involvement at the time of initial diagnosis were determined for each subtype of lymphoma. Thirty-three patients (21.8%) had bone marrow involvement. The frequency of bone marrow involvement was high for undefined and convoluted lymphocyte lymphomas (66.6%) and low to intermediate for follicular centre cell (20.3%) and small lymphocyte lymphomas (20.0%). Within the FCC lymphomas the non-cleaved cell type had a higher incidence of marrow involvement than the cleaved cell type (41.6% vs 8.9%). The follicular and diffuse histologic patterns in the diagnostic node did influence the incidence of marrow invasion in the non-cleaved cell type (75% vs 25%). A low incidence of marrow involvement was observed for the immunoblastic lymphomas (14.2%); evidence of marrow infiltration was never observed in patients with true histiocytic lymphomas.

Radiation therapy for local-regional recurrences of rectal carcinoma following primary surgery.

AIMS AND BACKGROUND: Several studies have emphasized the role of radiation therapy for patients with pelvic recurrences of rectal carcinoma following primary surgery. The occurrence of local-regional relapse usually means a poor prognosis and often a poor quality of life, so that different authors consider the prognosis of patients relapsing after surgery worse than those with primary inoperable tumors or those with residual disease after resection. METHODS: Between January 1988 and January 1995, 43 patients with local recurrence of rectal carcinoma were treated at our Institution. Twenty-three had previously been operated by abdominoperineal resection and 20 by anterior resection. Thirteen cases also received adjuvant chemotherapy. All patients underwent irradiation with a 6-15 MeV linear accelerator; 8 (19%) received a total dose of up to 45 Gy on the pelvis and 35 (81%) higher than 45 Gy. Eighteen cases (42%) underwent 3-6 courses of chemotherapy with 5-fluorouracil and folates during radiation. RESULTS: Treatment tolerance was satisfactory. All cases underwent restaging at 45 days from completion of treatment. Sixteen cases (37%) showed a radiologic response > 50%. Median overall survival after relapse was 18.8 months. There were no statistical significant differences in survival between patients treated exclusively with radiation and those treated with chemo-radiotherapy (17 vs 22 months). The results of patients who received doses higher than 45 Gy were statically better (P < 0.05) than those irradiated up to 45 Gy. A slight increase in survival was demonstrated in cases submitted to radical surgery after combined treatment (25 months). Twenty-seven cases (63%) obtained pain control after radiation therapy (median pain remission, 11 months). CONCLUSIONS: Our results seem to encourage radiation therapists, surgeons and oncologists to have a more curative attitude in the treatment of selected patients with local-regional recurrences of rectal cancers by using multi-modality therapy.

Hodgkin's disease stage I and II with exclusive subdiaphragmatic presentation. The experience of the Departments of Radiation Oncology and Hematology, University "La Sapienza" of Rome.

During the period 1978 to 1994, 1054 patients with Hodgkins's disease were evaluated and treated at the Departments of Radiation Oncology and Hematology, University "La Sapienza", Rome. A total of 549 patients presented with clinical or pathological stage I and II; 37 of these had Hodgkin's disease below the diaphragm (BDHD), and 512 above the diaphragm (ADHD). A comparison of patients with BDHD versus those with ADHD showed that the first group had a higher male to female ratio. A comparison of cases with stage II BDHD versus those with stage II ADHD showed that patients with BDHD were older (48 years vs 28 years), had different histologic features and a higher incidence of systematic symptoms (67% vs 33%). Stage II BDHD patients had a worse prognosis; in fact, there were significant differences in the overall survival and relapse-free-survival rates for cases with stage II BDHD versus those with stage II ADHD (overall survival, 46% vs 80%, P<0.001; relapse-free survival, 44% vs 69%, P<0.005). Stage was found to be the most important prognostic factor for BDHD cases without systematic symptoms treated with radiation therapy alone. The type of infradiaphragmatic presentation (intra-abdominal vs peripheral disease) did not influence outcome, probably due to the more aggressive therapy received by the intra-abdominal group. Treatment recommendations for BDHD cases should be tailored to the stage and the presence or absence of intra-abdominal localization. For patients with stage IA extended fields, irradiation (inverted Y) is sufficient. However, combined modality therapy should be the treatment of choice for stage II cases, particularly in the presence of intra-abdominal disease. Patients with systematic symptoms also require combined modalities.