Risk of malignancy from thyroid nodular disease as an element of clinical management of patients with Hashimoto's thyroiditis.

BACKGROUND: Many studies have investigated the association between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC), but clinical management of this condition has never been addressed specifically, even in recent guidelines. Surprisingly the likelihood of a nodule as being cancerous in a CLT has never been explicitly expressed in terms of relative risk. METHODS: This study was based on a retrospective analysis of 404 patients undergoing total thyroidectomy. RESULTS: Sixty-nine patients (17.1%) had histological findings of true CLT, and 36.2% had concurrent PTC versus 22.6% of patients in the non-CLT group (p < 0.05), with a tumour risk in the CLT group of ×1.6 (95% CI = 1.21-1.94, likelihood ratio = +1.63). CONCLUSIONS: Patients with CLT and a nodular condition have a ×1.6 increased risk of harbouring a PTC. Moreover, these patients develop multicentric PTC more frequently, and, as a result, total thyroidectomy should always be considered.

The use of different Peg-interferon alpha-2b regimens plus ribavirin in HCV-1b-infected patients after rapid virological response does not affect the achievement of sustained virological response.

In patients with chronic hepatitis C, rapid virological response (RVR) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response (SVR). The aim of this study was to investigate the outcome of different pegylated interferon-alpha2b (Peg-IFN-alpha2b) dosages plus ribavirin (RBV) in patients with RVR. Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-alpha2b (1.5 microg/kg/week) in combination with weight-based RBV doses (800-1200 mg/day). Thirty-one patients (68.9%) attained RVR at week 4 of therapy, while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders (EVR). The 31 RVR patients were randomized to receive either RBV plus 1.5 microg/kg/week (17 pts) or 1.0 microg/kg/week (14 pts) of Peg-IFN-alpha2b for the remaining 44 weeks. The two groups were matched for age, sex, baseline alanine aminotransferase levels, viral load and fibrosis score. After 6 months of post-treatment follow-up, the prevalence of SVR was 94.1% (16/17) among RVR patients treated with 1.5 microg/kg/week and 92.8% (13/14) in RVR patients treated with 1.0 microg/kg/week (P = not significant). A high-baseline viral load (P = 0.01) and bridging fibrosis/cirrhosis (P = 0.02) negatively influenced the likelihood of achieving RVR. On the contrary, the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group. Finally, the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients (1/4 = 25%vs 29/31 = 93.5%; P = 0.0058), because of a high prevalence of post-treatment relapse among patients with EVR.

[Clearances in automated intermittent peritoneal techniques: a new formula to use morning blood sampling]. / Clearances in tecniche peritoneali automatizzate intermittenti: una nuova formula per utilizzare il prelievo ematico del mattino.

According to the main guidelines, dialysis adequacy monitoring is fundamental in the management of patients on peritoneal dialysis. In order to avoid mistakes in the calculation of the peritoneal urea and creatinine clearance in patients on dialysis with intermittent techniques, the collection of blood samples about 6 hours after the end of the dialysis session is advised. In fact, because the creatinine and urea values at the end of dialysis (the morning values in NIPD) are the lowest, the resulting clearances could be overestimated. The mean values between the start and the end of the dialysis session are considered the gold standard. However, collecting a blood sample at 2.00 p.m. may be difficult and uncomfortable both for the nurse and the patient. In this paper we present two formulas (the first for urea and the second for creatinine) which, starting from the values at the end of dialysis, predict the values at the beginning of the session and consequently the mean values. The aim of this study was to validate the formulas by evaluating their capability to predict the mean urea and creatinine values when only end-of-dialysis blood sampling was performed. Statistical analysis was carried out using the Bland-Altman test. The two formulas proved able to predict the mean urea and creatinine values; the differences between the measured and calculated values were not statistically significant.

[Two centers with a native fistula prevalence higher than 90%: organization and activity]. / Due centri accomunati da una prevalenza di fistole con vasi nativi maggiore del 90%: attività e modelli organizzativi a confronto.

Vascular access (AV) dysfunction is a major cause of morbidity and hospitalisation in hemodialysis population. Despite of guidelines statements which consider native arteriovenous fistula (nAVF) the gold standard, epidemiological studies still show a decline in their prevalence with an increase of central venous catheters (CVC). In this study we compared the activity of two Dialysis Units both characterized by a high prevalence (> 90%) of nAVF, in order to highlight the possible reasons. No collaboration existed between the two centres until the decision to design this work. The "policy" on creation and management of vascular access and organizational models of the two centres were assessed, in particular focusing on surgeons, presence of dedicated nephrologists, preoperatory ultrasound evaluation, follow-up and diagnosis of complications, resort to interventional radiology, complications management, in particular the timing of intervention after AVF thrombosis. Of the two dialysis populations were analysed: age, time on dialysis, coexistence of diabetes and the prevalence of various types of vascular access to 31 December 2007. It was evaluated the AV incidence in the last 4 years. The statistical analysis was performed by T student and Chi square tests. There were no substantial differences in the organizational models of the two centres, which had both a routine ECD use in preoperatory mapping and in monitoring of complications; in case of thrombosis both centres performed surgery within 12-24 hours; in case of stenosis both centres performed the correction, surgical or by angioplasty, within 15 days from the diagnosis. Another common element was the presence of a multidisciplinary team with a interventionist nephrologist, a vascular surgeon and a vascular interventional radiologist, where nephrologist has the coordination role. The data analysis showed a prevalence of nAVF in the two centres of 92.5% and 96.1%, Pescara and Lecce respectively, with a prevalence of forearm nAVF of more than 80% and 90% respectively. The analysis of incident interventions showed high percentage of forearm AVF in case of revisions for complications (stenosis, thrombosis), and a little recourse to proximal AVF and graft.

Microcarcinoma and incidental carcinoma of the thyroid in a clinical series: clinical behaviour and surgical management.

OBJECTIVES: Papillary thyroid microcarcinomas (PTM) have not yet an agreed clinical management. The Authors compared PTMs with papillary thyroid carcinoma of larger size (LPTC) and incidental and not-incidental carcinomas. MATERIALS AND METHODS: Review of clinical data of 67 patients (54 women, 13 men) prospectively stored in a standardised way in an electronic patient record system. RESULTS: There were 36 cases of microcarcinoma (53.7%). Differences were not significant between PTM and LPTC groups as to patients personal data, TNM and MACIS staging, nodal involvement (8.3% vs 19.3%) and multifocality (25% vs 38.7%) while capsular invasion was significantly higher in LPTC (25% vs 54.8%). Nineteen incidental tumors were detected at pathological examination and they were all microcarcinomas. They were smaller than the remaining 17 not-incidental microcarcinomas but showed a similar clinical behaviour. There were not cancer related deaths nor recurrences in the follow up period in any group. CONCLUSIONS: Despite the excellent prognosis of PTM, a subset of these tumours shows aggressive biological and clinical features, like nodal or capsular invasion and multifocality. Actually, with the exclusion of size, they do not show any relevant difference from differentiated thyroid carcinoma of larger size. Since predictive cytogenetic markers are still missing, their treatment should then be the same as for conventional thyroid cancers.

HMGB1-Induced Cross Talk between PTEN and miRs 221/222 in Thyroid Cancer.

High mobility group box 1 (HMGB1) is an ubiquitous protein that plays different roles in the nucleus, cytoplasm, and extracellular space. It is an important DAMP molecule that allows communication between damaged or tumor cells and the immune system. Tumor cells exploit HMGB1's ability to activate intracellular pathways that lead to cell growth and migration. Papillary thyroid cancer is a well-differentiated tumor and is often used to study relationships between cells and the inflammatory microenvironment as the latter is characterized by high levels of inflammatory cells and cytokines. Anaplastic thyroid cancer is one of the most lethal human cancers in which many microRNAs and tumor suppressor genes are deregulated. Upregulation of microRNAs 221 and 222 has been shown to induce the malignant phenotype in many human cancers via inhibition of PTEN expression. In this study we suggest that extracellular HMGB1 interaction with RAGE enhances expression of oncogenic cluster miR221/222 that in turn inhibits tumor suppressor gene PTEN in two cell lines derived from human thyroid anaplastic and papillary cancers. The newly identified pathway HMGB1/RAGE/miR221/222 may represent an effective way of tumor escape from immune surveillance that could be used to develop new therapeutic strategies against anaplastic tumors.

Onset of hepatocellular carcinoma in a non-cirrhotic patient affected with haemochromatosis.

The increased incidence of hepatocellular carcinoma in patients affected with haemochromatosis has previously been attributed to cirrhosis. However, some cases of hepatocellular carcinoma without cirrhosis have recently been reported in patients with haemochromatosis, leading to reconsideration of the role of iron in the tumorigenesis of hepatocellular carcinoma. We describe a 79 year old male patient affected with haemochromatosis and with a multinodular hepatocellular carcinoma, but without any evidence of cirrhosis. The absence of any other cancer risk factor (alcohol abuse, liver viral infections, heredity) has lead us to reconsider the possible role of iron as a direct carcinogen in the onset of hepatocellular carcinoma in patients with haemochromatosis.

Fine needle aspiration biopsy in the preoperative management of patients with thyroid nodules.

The aim of this study was to evaluate the role of Fine Needle Aspiration Biopsy (FNAB) in the preoperative diagnostic management of patients with solitary or dominant thyroid nodules. This study was performed on 1054 patients followed for various thyroid disorders during a three year period (1992-1995). One hundred thirty eight patients were surgically treated, 61 after cytological indication and 77 after clinical indication, of these, 67 were cytologically negative and 10 were not conclusive. The cytological diagnosis was compared to the final histological result. Among the 138 cases, 27 were malignant, 39 were adenomas and 72 were benign lesions. Of the 67 cytologically negative cases, 63 (94%) were histologically benign, three were papillary carcinomas and one was an oxyphilic adenoma. Of the 45 cytologically suspicious aspirates, four were malignant neoplasias, 38 were follicular adenomas, two were hyperplastic goiters and one was an Hashimoto thyroiditis. All the 16 cytologically positive cases, were confirmed histologically. The limits of FNAB, which emerge from our and other studies, were based mainly in the difficulty of discriminating follicular adenomas from well differentiated follicular carcinomas. Nevertheless, FNAB with ultrasonographic support, has been unanimously accepted as a guide test in the selection of patients with thyroidal pathology who need surgery.

Multiple viral infections in a group of intravenous drug users: hepatitis B virus exposure is the risk factor.

OBJECTIVE: Infection with hepatotropic viruses is associated with a variable degree of liver disease, and there is evidence that more severe lesions are related to the association with another viral infection. The aim of this investigation is to establish the relationship between different viral infections occurring in the same individual and the presence and progression of liver disease. DESIGN: The study population comprises 754 intravenous (IV) drug abusers exposed to hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or cytomegalovirus (CMV). All individuals were followed for an average of 2 years. Liver disease was assessed by liver function tests, 99m-technetium (99mTc) liver scintigraphy, and also by liver biopsy in a subset (n = 136) of patients. The different viral patterns and presence of disease were analysed by logistic regression, and the risk factors were calculated. Contingency tables of patients with single or associated infections were drawn up to evaluate progression of liver disease. RESULTS: Association of HIV with at least one other viral infection was constant. Surface antigens of HBV (HBsAg) were always associated with HIV (n = 19); in this group, 18 patients had signs of liver disease. A past infection with HBV, as revealed by the presence of at least antibodies against the surface antigen (HBsAb) and antibodies against the core antigen of HBV (HBcAb), was detected in 463 patients (61.4%). The overall prevalence of HCV antibodies was 63.91% (n = 482). In 96.8% of the 406 patients tested, HCV-RNA was detected by reverse transcriptase polymerase chain reaction (RT-PCR). The majority of patients with high alanine transaminase (ALT) had anti-HBV antibodies in the presence of HCV (56.1%). At the end of follow-up, all of these patients showed signs of active liver disease, and scoring was significantly worse than in patients with either HBV or HCV alone. An infection/reactivation of CMV was found in patients previously exposed to HBV and with increased ALT values. CONCLUSIONS: Data emerging from this study reveal the association of HCV or CMV, or both, with a previous HBV infection, as demonstrated by HBsAb and HBcAb, and rapid progression of the disease in this group of patients. A previous HBV infection therefore appears to be an important risk factor for subsequent viral-related liver disease.

Vitiligo, autoimmune thyroiditis: a rare thyroid cancer arising with bone metastates on maxillofacial area.

An association between vitiligo and autoimmune thyroid disorders had previously been postulated. Thyroid disorders were found in 18.5% of 15,126 patients with vitiligo, on the basis of the anamnestic data. Then, we investigated 255 healthy relatives in whom we tested only T3, T4 and TSH. With the immunological investigation we detected a higher incidence of TMA in vitiligo patients and in the family members. Therefore, on the basis of the immunologic and thyroid pathology functional data, we observed a thyroid pathology in 25% of the 890 vitiligo patients and in 21.1% of their first degree relatives. Then, clinical observation enabled to discover that 3 of 15,126 patients had undergone exeresis for a thyroid carcinoma and in the 890 vitiligo patients, who had undergone particular investigations, we found a thyroid carcinoma in 3 subjects. In one case lymphnodal involvement and bone metastases in the maxillary district were found. The purpose of this work is to evaluate the incidence of thyrosis and of thyroid carcinoma in vitiligo patients observed for 20 years.

Expression of bcl-2, c-erbB-2, p53, and p21 (waf1-cip1) protein in thyroid carcinomas.

The study was carried out on 53 patients who had thyroid cancer with various degree of differentiation. We studied the expression of bcl-2, a-erbB-2, p53, and p21 ras protein. The protein encoded by bCL-2 proto-oncogene is implicated in the prolongation of cell survival by blocking programmed cell death, i.e. apoptosis. The role of p53 and bcl-2 genes in the regulation of apoptosis has important implications in oncogenesis. Wild-type p53 is thought to promote apoptosis, whilst mutant p53 has a similar effect on apoptosis as bcl-2 that is inhibition of programmed cell kinase activity. C-erb-2 protein overexpression is currently being evaluated as a potential risk factor in breast cancer patients? The ras gene family codes for a 21 kD protein (p21), which binds guanine nucleotides and possesses GTPase activity. Through this mechanism, the ras p21 protein participates in the control of cell proliferation, possibly as a signal transducer from cell surface receptors to the nucleus. Activation of ras genes has been implicated in neoplastic transformation of cells. The aim of our study is to evaluate the expression of these markers in thyroid carcinomas. All immunohistochemical study was performed in paraffin-embedded tissues pathology specimen. Any well differentiated tumor in our study was positive for bcl-2 protein. C-erb-2 immunostaining was present in tumor samples in 60% of cases. In most cases, specific membrane staining as well as a weak cytoplasmic positivity of tumor cells were seen. Immunoreactivity for p53 was positive only in 10% of cases. By immunostaining, p21 protein was expressed in 55% of the 53 tumors tested, with different degree of expression. Only some poorly differentiated tumours were positive for bcl-2, furthermore all markers tested were strongly positive in these tumours. In conclusion, our results indicate that bcl-2, c-erbB-2, p53, and p21 ras protein are differently expressed in thyroid carcinomas in relation to the degree of aggressiveness and differentiation.

What sedation to use during endoscopic procedure.

Many endoscopists sometimes prefer to perform endoscopies without anaesthetic support, using only benzodiazepines. Endogenous opioid peptides are believed to play an important role in the modulation of pain within the endogenous analgesic system. A group of 40 patients undergoing diagnostic and therapeutic Endoscopic Retrograde Cholangiography and Pancreatography (ERCP) was recruited. Patients were divided into 2 groups according to Visual Analog Scale: pain 1-5 (Group A) and pain 6-10 (Group B). The beta-endorphin baseline values were significantly different between patients of Group A and Group B. Our data show that patients with levels of beta-endorphin over 8 pmol/L were less sensitive to pain, so that they become candidates for a traditional utilization of the benzodiazepines. However in the patients with beta-end levels less of 8 pmol/L should be suitable an anaesthetic as propofol because strong pain might provoke neurohumoral reflexes, cardiovascular alterations, and even a heart attack.

[Bifurcated prosthesis in infrarenal aortic position in stenosing lesions. Functional results]. / Le protesi biforcate in posizione aortica sottorenale per lesioni stenosanti. Risultati funzionali.

Fifty-eight patients operated upon of infrarenal aortic bifurcated grafts for occlusive disease, in a 6-year period, have been followed-up with a minimum interval of 2 years. The patients were in claudication stage in 63% of the cases and in critical limb threat ischemia in 37% Bypass consisted always in a bifurcated knitted dacron graft either pre-coagulated or sealed. Infrarenal aorta has always been the donor axis, whereas distal anastomosis has been performed on both common femoral in 80% of the cases, on at least one external iliac in 20%. In 5% of the cases a femoro-popliteal bypass has been associated to the main procedure. Postoperative mortality was 3.5%. The occlusion of a prosthetic branch in the postoperative period occurred in one case, requiring a major amputation. Seven patients (12%) presented 11 late thrombosis of one prosthetic branch or both on an interval varying from 4 to 62 months. Eight occlusions required reintervention. Only one, lethal, late prosthetic sepsis was recorded. In a mean interval of 54 months, a good or fair functional result was achieved in 93% of the patients. Out of 22 patients specifically questioned upon, 82% returned to their normal work activity, whereas 18% retired but had a fully normal everyday's life. Sexual function was ameliorated or unchanged in 67% of the cases, while it was impaired in 33%. Eighty-seven percent of the followed-up patients did not require any further hospitalisation for atherosclerotic disease, while 13% of them experienced subsequent hospitalisation or reintervention for progression of the disease either at the same or at different arterial sites. Overall good results support an aggressive attitude towards aorto-iliac-femoral grafting for occlusive disease.

[Papillary carcinoma of the thyroid: nosological aspects, prognostic factors and principles of therapy]. / Il carcinoma papillifero della tiroide: aspetti nosologici, fattori prognostici e principi di terapia.

Papillary carcinoma of thyroid, has not, until now, been considered prognostically and therapeutically clear, because it is not free from problematic questions regarding prognosis and treatment, though it has been studied for a long time. The Authors analyse this pathology under actual learning conditions, with reference to the nosologic, prognostic and therapeutic aspects.

[Guidelines for the routine assessment of respiratory surgical risk: thoracic radiography]. / Linee guida per la valutazione routinaria del rischio chirurgico respiratorio: la radiografia del torace.

Through the three years between June 1995 and June 1998 the authors applied an evaluation schedule for the respiratory surgical risk to all the patients undergoing general surgery. Chest X-ray was included in this schedule as a first-level test and it was performed systematically on all the patients. The purpose of the study was to verify the effectiveness of chest X-ray as a routine examination of the respiratory performance, evaluating its predictive value on 1715 cases. The routine employment of this preoperative test on patients resulting risk-free at an accurate clinical anamnestic examination doesn't seem to be justified, basing on the preliminary results achieved. Therefore, chest X-ray should be considered a second-level test, to be performed on the basis of a precise clinical query only. This way a significant health-care cost reduction could be achieved, without affecting the quality of patient's management.

[Clinical significance of thyroid nodule calcification]. / Significato clinico delle calcificazioni nei noduli tiroidei.

To confirm the predictive value of calcifications in thyroid nodules as a risk factor for malignancy and to detect specific aspects for tumours, in a set of 175 patients--30 papillary carcinoma (PC) and 145 multinodular goiters (MNG) with dominant nodule--calcifications were detected by ultrasound scan. Calcifications were significantly more frequent in PC than in MNG (40% vs 20.7% p < 0.05) but their considered characteristics (size, number, position, location in the gland, sonographic features of the nodule) did not show any particular difference between PC and MNG. The frequency of calcifications in our series was higher in older patients (mean age 58.7 +/- 13.3 vs 51.1 +/- 12.7 in patients without calcifications, p < 0.001) and this could imply that their onset is time-dependent. Calcifications can be a useful indicator of enhanced risk, to be considered in the overall process of surgical decision making.

[Fournier's syndrome: diagnostic and therapeutic assessment]. / La sindrome di Fournier: inquadramento diagnostico e terapeutico.

Fournier's syndrome is a disorder involving perineum and scrotum caused by invasive anorectal infection. Aerobic and anaerobic bacteraemia can lead to septic toxicity. Hence the importance of the multidisciplinary treatment and urgent surgical procedures including drainage and necrotic tissue removal is stressed. A case of Fournier's syndrome is reported.

[Biodegradable compression ring in intestinal anastomosis]. / L'anello bioframmentabile a compressione nelle anastomosi intestinali.

The Authors report their experience with the use of biofragmentable anastomosis ring ("Bowel Anastomosis Ring" B.A.R.--Valtrac): 34 patients underwent colic resection and bowel anastomosis by B.A.R. No complications related to the anastomosis were recorded. The ring was always discharged in the third postoperative week and the endoscopic follow up showed no late complications. It is concluded that B.A.R. is a safe technique and represents a good alternative to hand or mechanical anastomosis with a favorable cost/benefit ratio.

Prospective comparative evaluation of quantitative-elastosonography (Q-elastography) and contrast-enhanced ultrasound for the evaluation of thyroid nodules: preliminary experience.

PURPOSE: To assess the effectiveness of semiquantitative elastosonography (Q-elastography) compared with contrast-enhanced ultrasound (CEUS) in differentiating the nature of thyroid nodules. METHODS AND MATERIALS: Forty-eight consecutive patients (35 males, 13 females, range: 34-69 years, mean: 49.4 years), candidate to surgery, previously detected at color-Doppler ultrasound (CDUS), were prospectively examined with elastosonography with dedicated semiquantitative software (Q-Elastography, Toshiba XG) and CEUS (Technos Mylab 70 Gold X, and Toshiba XG) before surgery. CEUS and elastosonography were evaluated by two investigators in consensus. Comparison between the CEUS pattern and elastonographic strain ratio observed and expected frequencies for the diagnoses was evaluated with χ(2) test or with Fisher exact test. RESULTS: Fifty-three nodules (19 papillary carcinoma, 32 hyperplasia, and 2 follicular adenoma) in 48 patients were available for analysis. Regarding echogenicity score, sensitivity, specificity, PPV and NPV of conventional US were 81%, 50%, 56%, 77%; according to Q-elastography, sensitivity, specificity, PPV and NPV were 95%, 88%, 97% and 91% respectively; whereas concerning CEUS, sensitivity specificity PPV and NPV were 79%, 91%, 83% and 89% respectively. Both CEUS and Q-elastography were more specific than US (p<0.01), with not statistical significant difference with regard to sensitivity. CONCLUSIONS: The results of the present study suggest that Q-elastography is a valuable tool in the characterization of thyroid nodules and it seems to be more sensitive than CEUS.

Increasing diagnostic accuracy for thyroid nodules by an integrated multivariate approach: a methodological study.

OBJECTIVES: Current guidelines for diagnostic management of thyroid nodules are based on a linear approach, using categorial classifications to cluster diagnostic findings and they still lead to unnecessary surgery. A diagnostic scoring system, based on clinical, cytological and ultrasound findings is described. MATERIALS AND METHODS: Two groups of patients (168 and 55 pts) were used to compute a multivariate model and the discriminating threshold by ROC curves. The performance of the derived scoring system was assessed by a simulation on a third group of 60 patients, who had undergone surgery according to current guidelines. RESULTS: The scoring system displayed a sensitivity of 100%, specificity 53.3%, positive and negative predictive values of 68.1% and 100%. According to the scoring system, 16 out of 60 operations would have been saved. CONCLUSIONS: A scoring system can take into account in a more accurate way the full informative content of the fine-grained description of diagnostic and clinical features.