PAPILLARY THYROID CANCER IS CHARACTERIZED BY ALTERED EXPRESSION OF GENES INVOLVED IN THE SUMOYLATION PROCESS.

Small Ubiquitin–like MOdifier (SUMO) proteins are small protein modifiers capable of regulating cellular localization and function of target proteins. Over the last few years, a relevant role has been demonstrated for sumoylation in the modulation of important cellular processes, including gene transcription, DNA repair, cell-cycle regulation and apoptosis. Components of the sumoylation machinery have been found deregulated in different human cancers, and are thought to significantly affect cancer cell progression. In the present study we sought to analyze the expression of all the components of the sumoylation machinery in a case study comprising 77 papillary thyroid cancers (PTC) and normal matched tissues. In particular, we evaluated the expression of the SENP1 to SENP8 (SENtrin-specific proteases), SAE1 (SUMO1 activating enzyme subunit 1), UBA2 (UBiquitin-like modifier activating enzyme 2), UBC9 (UBiquitin conjugating enzyme 9), RanBP2 (RAN binding protein 2), MSMCE2 (Non- SMC element 2), CBX4 (ChromoBoX homolog 4), PIAS1 to PIAS4 (protein inhibitor of activated STAT), ZMIZ1 (zinc finger, MIZ-type containing 1) and ZMIZ2 (Zinc finger, MIZ-type containing 2) by means of quantitative RT-PCR. In most of the PTC examined we observed a significant alteration in the mRNAs of SENP8, ZMIZ1, SAE1, PIAS1 and PIAS2. These tended to be reduced in about 50 to 66% of cases, and unchanged or increased in the remaining ones. Univariate and Kaplan-Mayer analyses documented the lack of association between the expression of the above 5 genes and clinicopathological parameters. Only SAE1 was significantly higher in female PTC tissues, in respect to male PTC tissues (p=0.021), and SENP8 was significantly lower in TNM stages III-V, with respect to stages I-II (p=0.047). In conclusion, we demonstrated that the expression of SENP8, SAE1, PIAS1, PIAS2 and ZMIZ1 is deregulated in the majority of PTC tissues, likely contributing to the PTC phenotype. However, differently from other human cancers, their mRNA level does not represent a prognostic biomarker in PTC patients.

Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer.

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs. 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues.

Achieving the learning curve in total thyroidectomy: a prospective evaluation on resident's training by CUSUM and KPSS analysis.

INTRODUCTION: Total thyroidectomy (TT) is one of the most common procedures among general and endocrine surgeons worldwide. The conventional approach by neck incision is still the most frequently used, despite the growth of mini-invasive approaches. Controversies exist about the optimal learning curve for resident surgeons approaching this procedure. The aim of this study was to compare TT performed by experienced surgeons and residents in two academic hospitals, to define the correct shape of the specific learning curve. METHODS: Between January 2016 and December 2018 patients undergoing TT in two academic departments were prospectively enrolled. In each department patients were divided into four groups: a reference group (A), consisting of 50 consecutive patients operated on by a senior surgeon, and three other groups (B, C, D) of 50 patients each where thyroidectomy was carried out by three different general surgery residents in their last 3 years of residency, respectively. Data were analysed by CUSUM and KPSS tests in order to compare operative time (OT) and its stabilisation during the learning curve. RESULTS: Data from CUSUM test reported that residents could perform TT with OT similar to the senior surgeon after approximately 25-30 procedures, while the KPSS test showed that residents became more stable after 30 procedures, with no increase in perioperative complications. CONCLUSIONS: This prospective study shows how a specific training in thyroid surgery can be reliable thanks to experienced tutors, and confirmed that the effect of dedicated and programmed training may result in positive outcomes for patients requiring thyroidectomy.

[Hormone replacement therapy after total thyroidectomy. Can the combined treatment be considered effective to get metabolic adequacy? Preliminary results]. / Terapia ormonale sostitutiva dopo tiroidectomia totale. Il trattamento ormonale combinato può essere considerato efficace strumento di adeguatezza metabolica? Risultati preliminari.

INTRODUCTION: Even if T4 is standard treatment for hypothyroidism after thyroidectomy, a treatment with T4 plus T3 has been proposed as an alternative reproducing carefully the physiology of the thyroid. We performed an observational study about the effects of the combined replacement therapy with T4 and T3 in patients who underwent total thyroidectomy. PATIENTS AND METHODS: Fifty thyroidectomized patients (not for cancer), in T4 replacement therapy, were included in the study. Such a therapy has been changed by administering T3 and T4 in proportion 1/16. Adverse effects, clinical parameters and general health perceptions (SF36 Questionnaire) have been considered at the time of enrollment (T0), after 30 days (T1) and after 60 days (T2). RESULTS: No differences in weight, cardiac frequency and blood pression have been found between T0 and T2. A not statistically significant reduction has been found in total cholesterol (3 mg/dL) and triglycerides (3.29 mg/dL) levels. A reduction of complaints referred by the patients at T0 has been revealed in T2: anxiety from 21 to 13 patients; headache from 22 to 13; tiredness from 17 to 8 (p<0.05); sleepiness from 25 to 15 (p<0.05). About the questionnaire, in the General Health Perception sub-score has been found a not significant increase of the parameter. DISCUSSION AND CONCLUSIONS: T4 replacement therapy is of proved efficacy, notwithstanding some complaints afflict a share of patients. To improve the quality of life of these patients, we consider relevant the reduction of complaints and the improvement of well-being and cognitive function obtained by the combined T4 and T3 treatment. Moreover, even if the production of T3 from T4 usually ensures euthyroidism in all tissues, contemporary pathologies and alterations determined by the oldness can disturb the enzymatic activity, which is the essential requirement of T4 therapy. These preliminary findings in a small group of patients encourage further studies on a larger patient population.

Thyroiditis and oncocytic carcinoma: incidental association? A case report.

BACKGROUND: Several studies have reported an association between Hashimoto's disease and thyroid carcinoma although the cause/effect relationship is still controversial. CASE REPORT: In this paper we report the case of a 38-year-old female who first presented with a clinical history of Hashimoto's thyroiditis. Ultrasound examination showed a diffuse thyroid irregularity more pronounced in the right lobe. FNAC (Fine Needle Aspiration Cytology) was performed in this area, and the cytological diagnosis was "Hashimoto's thyroiditis". The patient underwent clinical follow-up. Two years later, an ultrasound examination showed a nodular lump in the area previously aspirated. A new FNAC evidenced a Hurthle cell neoplasia. Therefore, the patient underwent surgery. The histological diagnosis was "Hurthle cell carcinoma". CONCLUSION: In the present case, the clinical and ultrasound history suggest the development of a malignant lesion strictly related to thyroiditis, as previously reported by other studies on papillary carcinoma. A cause-effect relationship between chronic lymphocytic thyroiditis and oncocytic neoplasia is still a matter of controversy. Therefore, patients suffering from chronic thyroiditis require a careful follow-up and, in case of nodules development, FNAC is recommended.

Fine needle aspiration and core needle biopsy techniques in the diagnosis of nodular thyroid pathologies.

It is widly accepted that Fine Needle Aspiration Biopsy (FNAB) is the main test to distinguish benign from malignant thyroid lesions. Nevertheless, this technique presents some limits such as the possibility of false-negative or inadequate samples and it is unable to cytologically discriminate among adenomathosus goiter, follicular adenoma and well-differentiated follicular carcinoma. The aim of this study was to evaluate the possibility of restricting these limitations using Core Needle biopsy (CN) technique. Therefore we selected for CN, 40 out of 136 patients who underwent FNAB during a one year period; among these patients only 32 agreed a to this technique. Forty-two out of 136 patients underwent surgery; 29 of them were subjected to both biopsies. Sixteen of the diagnostic microbiopsies have been histologically confirmed. We had no discordant cases between cytological and microhistological diagnosis, except for one case which appeared cytologically colloid goiter, microhistologically follicular neoplasm and histologically follicular adenoma. In this case it was not possible to microhistologically discriminate benign from malign follicular lesion. In our experience not all patients accepted CN biopsy as well as FNAB and, moreover, this technique showed no advantage over FNAB diagnosis. On this base we think that actually FNAB should be the main procedure in the diagnosis of the thyroid lesions. It is easily performed, accepted by the patients and has a low cost-benefit ratio. If the sample is not diagnostic it can be easily repeated and false-negative cases could be discovered thanks to an adequate clinical and ultrasonographical follow-up of the patients.

Isolated intestinal neurofibromatosis of colon. Single case report and review of the literature.

Isolated intestinal neurofibromatosis of the colon is a most unusual disease: from 1937 to 1999 only 12 cases have been reported. The differential diagnosis and treatment of this lesion are very difficult. A review of the literature is made and personal experience in the diagnosis and treatment of a case in a 68-year-old female is described.

Primary non-Hodgkin lymphoma of the parotid gland.

The rarity of primary non-Hodgkin lymphomas of the parotid gland triggers this report on a case treated and now in the fourth year of follow-up, which offers the opportunity for a review of the literature on the subject. The paper also describes the criteria for accurate classification, the diagnostic tools available and the problems of differential diagnosis. Treatment protocols and survival are also considered.

Neuroendocrine tumors of the gastroenteric canal. Anatomopathological and diagnostic-therapeutic definition. Description of a case with a rare cecal localisation.

The authors take the case of a neuroendocrine tumour of the cecum as the starting point for an analysis of the anatomopathological and diagnostic-therapeutic aspects of these neoplasms. Furthermore, the authors underline that neuroendocrine tumours (NET) of the colon represent an extremely rare nosological entity and that they are heterogeneous from a clinical and biochemical point of view, thus making a reliable preoperative diagnosis a problem that is still difficult to resolve today.

Diagnosis controversies for adrenal ganglioneuroma.

The authors report a case of adrenal ganglioneuroma which was incidentally diagnosed performing preoperative examination for a sigmoid carcinoma. The authors took this finding as a starting point to underline the rarity of this condition and its chance discovery, this being due to the rare presence of signs and symptoms and its frequent association with other synchronous neoplasms; all this makes differential diagnosis rather difficult.

Unusual breakage of a plastic biliary endoprosthesis causing an enterocutaneous fistula.

OBJECTIVE: The objective of our study was to illustrate a case of endoscopically placed biliary stent breakage. METHODS: A72-year-old woman with a prolonged history of cholangitis following laparoscopic cholecistectomy was referred to our institution 8 years ago. Dilatation of the intra- and extrahepatic biliary tree and a benign stricture at the cystic confluence were observed at US and endoscopic retrograde cholangiopancreatography (ERCP). A 12-F gauge plastic endoprosthesis was placed. In the absence of any symptoms, breakage of the stent was revealed 18 months later at plain radiology. Eight years later an enterocutaneous fistula occurred originating from a jejunal loop containing the indwelled distal part of the stent. Surgery was undertaken and the distal part of the stent removed with the perforated jejunal loop. The proximal part was successively endoscopically removed. CONCLUSIONS: Disruption of a biliary endoprosthesis is observed in patients in whom the stent is kept in situ for a long period or consequent to exchange. The removal and exchange is mandatory when the stent disruption is followed by cholangitis. In the current case, because of the absence of any symptoms the removal of the stent was not attempted. Immediate endoscopic removal of the prosthetic fragments seems to be the treatment of choice for replacement of a new stent.

Fast determination of Sudan I by HPLC/APCI-MS in hot chilli, spices, and oven-baked foods.

The Commission Decision of EC dated 20 June 2003, on emergency measures concerning hot chilli and hot chilli products coming into any EC member state, required that the consignments of such products should be accompanied by an analytical report showing that they are free of artificial dye Sudan I. The opportunity to set a confirmatory method is evident, and the paper proposes a HPLC/APCI-MS method useful for identification and quantitation of Sudan I, also at very low levels in hot chilli, other spices, and oven-baked foods. Validation data are reported.

Prognostic significance of primary-tumor extension, stage and grade of nuclear differentiation in patients with renal cell carcinoma.

Surgery remains the preferred therapy for renal cell carcinoma. The various adjunctive or complementary therapies currently yield disappointing results. Identifying reliable prognostic factors could help in selecting patients most likely to benefit from postoperative adjuvant therapies. We reviewed the surgical records of 78 patients who had undergone radical nephrectomy with lymphadenectomy for renal cell carcinoma, matched for type of operation and histology. According to staging (TNM), 5.1% of the patients were classified as stage I, 51.3% as stage II, 29.5% as stage III and 14.5% as stage IV. Of the 78 patients 40 were T2N0 and 21 T3aN0. Tumor grading showed that 39.7% of the patients had well-differentiated tumors(G1), 41.1% moderately-differentiated (G2), and 19.2% poorly-differentiated tumors (G3). Overall actuarial survival at 5 and 10 years was 100% for stage 1; 91.3% at 5 years and 83.1% at 10 years for stage II; 45.5% and 34.1% for stage III; and 29.1% and nil for stage IV (stage II vs stage III p = 0.0001). Patients with tumors confined to the kidney (pT2N0) had better 5- and 10-year survival rates than patients with tumors infiltrating the perirenal fat (pT3aN0) (p = 0.000006). Survival differed according to nuclear grading (G1 vs G3 ; p = 0.000005; G2 vs G3; p = 0.0009). In conclusion our review identified tumor stage, primary-tumor extension, and the grade of nuclear differentiation as reliable prognostic factors in patients with renal cell carcinomas.

Subcutaneous metastasis of pancreatic cancer in the site of percutaneous biliary drainage.

A subcutaneous metastatic lesion from a carcinoma of the pancreas or common bile-duct along the tract of a percutaneous transhepatic biliary drainage is a rare finding. Prompted by a case that came to our observation by chance, we reviewed the literature and analysed the 29 cases collected. Neoplastic cell seeding along a percutaneous drainage tract, albeit rare, must be kept in mind. The complication can be avoided if patients at risk, whenever possible, undergo endoscopic drainage.

[Comparative study of the effectiveness of imipenem versus ceftazidime and ceftriaxone in the prevention of postoperative infections]. / Studio comparativo sull'efficacia dell'imipenem versus ceftazidime e ceftriaxone nella profilassi delle infezioni postoperatorie.

A comparative study was performed on the efficacy, safety and tolerability of three different antibiotics (imipenem, ceftazidime, ceftriaxone) in the prevention of postoperative infection. Evaluations were made on the basis of the results obtained in a group of 90 patients subdivided into three matched groups each of which was treated with one of the three compounds. The trend of cutaneous temperature showed differences at the limit of significance (p congruent to 0.05). Variations in leucocyte concentrations showed an analogous pattern in all patients, although there were fewer and with a shorter duration in subjects treated with imipenem. The wound healing process was improved in patients receiving prophylactic antibiotic treatment in the form of imipenem (0.01 < p < 0.05) who also showed a greater respect for therapeutic protocols (80%), a higher percentage of remission of fever and a shorter mean hospital stay (9 days). In the light of these preliminary results the authors express their favourable judgement regarding the choice of imipenem for the prophylaxis of postoperative infection; however, each of the three protocols showed a considerable prophylactic capacity as well as good tolerability and ease of use.

Surgical treatment of multinodular goiter: incidence of lesions of the recurrent nerves after total thyroidectomy.

The problems concerning surgical goiter treatment are discussed, particularly the morbidity of total thyroidectomy and possible injury to recurrent nerves in comparison to the partial resection of the gland. We discuss our case material and review the literature. We conclude that total thyroidectomy seems to be the most effective surgical procedure with lower morbidity than subtotal thyroidectomy.

[Use of mechanical staplers in colorectal resections. Personal experience]. / L'utilizzazione delle suturatrici meccaniche nelle resezioni retto-coliche. Esperienza personale.

Staplers have introduced and continue to introduce benefits above all in terms of anastomotic procedures used in digestive tract surgery. A prime sector od application is rectal cancer in that mechanical anastomosis allows low rectal resections to be performed, thus reducing the number of abdominoperineal amputations, without negatively affecting the oncological radicality of exeresis. The authors review the cases operated by the 1st Chair of Surgical Pathology at "La Sapienza" Rome University during the period 1984-1993 when rectal anastomoses were systematically performed using mechanical staplers. On the basis of their personal experience and in line with the data reported in the literature, although there may be anastomotic complications, such ad dehiscence ad stenosis, it is possible to affirm that the use of staplers has led to benefits which, if evaluated as a whole, fully justify their cost which is still quite considerable.

[The experience of an outpatient service of breast pathology. I. The diagnostic procedure for screening]. / Esperienza di un servizio ambulatoriale di patologia della mammella. Nota I: iter diagnostico per lo screening.

The authors underline the importance of correct screening in the female population in order to achieve as early a diagnosis as possibly of malignant breast tumours. In view of the high frequency of this neoplasia, as well as the encouraging results of numerous tested diagnostic protocols in terms of their positive influence on the progress of this disease, the authors prepared a screening protocol within a breast pathology service, and report the results achieved during the course of about seven years. Out of a total of 5000 patients aged between 30 and 90 years old, a total of 261 cases were diagnosed with pathologies requiring surgery with a 57.9% incidence of carcinoma, among which, in compliance with reports in the literature, a net predominance was found of initial stage tumours with diameter of less than 2 cm (58.3%).