Endoscopic submucosal tunnel dissection vs conventional endoscopic submucosal dissection for large colorectal neoplasms: a single-centre retrospective study.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is still not widely used due to its technical difficulty and the risk of complications. Several techniques, such as traction techniques, pocket techniques and others, have been proposed to facilitate it. One modified pocket technique especially suitable for large lesions is endoscopic submucosal tunnel dissection (ESTD). The aim of this study was to evaluate the safety and efficacy of ESTD and compare ESTD to the conventional ESD (CESD) for treating large colorectal lesions. METHODS: The charts of consecutive patients referred to the Arcispedale Santa Maria Nuova (Reggio Emilia, Italy) for colorectal ESD between January 2014 and February 2021 for colorectal neoplasms > 40 mm were retrospectively analysed. The primary outcome of the study was the en bloc resection rate. Secondary outcomes were complete and curative resection rates, procedure speed, the adverse events rate and the recurrence rate. RESULTS: There were 59 patients (M:F ratio 29:30, median age 70 years [range 50-93 years]). Of 59 colorectal lesions > 40 mm, 25 were removed by ESTD and 34 by CESD. The en bloc resection rate was 100% in both groups and the complete resection rate was similar (ESTD 92% vs CESD 97.1%, p = 0.569), while the curative resection rate was higher in the CESD group, but not significantly (94.1% vs 76%, p = 0.061). Procedure speed was significantly faster with ESTD (22 vs 17 mm2/min, p = 0.045), and the overall incidence of adverse events was low (6.8%). Eight patients were referred to surgery due to non-curative resection. During follow-up, no recurrence was observed in either treatment group. CONCLUSION: ESTD achieves a very high en bloc resection rate and is faster than CESD.

Observed and estimated prevalence of Covid-19 in Italy: How to estimate the total cases from medical swabs data.

During the Covid-19 pandemic in Italy, official data are collected with medical swabs following a pure convenience criterion which, at least in an early phase, has privileged the exam of patients showing evident symptoms. However, there are evidences of a very high proportion of asymptomatic patients. In this situation, in order to estimate the real number of infected (and to estimate the lethality rate), it should be necessary to run a properly designed sample survey through which it would be possible to calculate the probability of inclusion and hence draw sound probabilistic inference. Unfortunately, the survey run by the Italian Statistical Institute encountered many field difficulties. Some researchers proposed estimates of the total prevalence based on various approaches, including epidemiologic models, time series and the analysis of data collected in countries that faced the epidemic in earlier times. In this paper, we propose to estimate the prevalence of Covid-19 in Italy by reweighting the available official data published by the Istituto Superiore di Sanità so as to obtain a more representative sample of the Italian population. Reweighting is a procedure commonly used to artificially modify the sample composition so as to obtain a distribution which is more similar to the population. In this paper, we will use post-stratification of the official data, in order to derive the weights necessary for reweighting the sample results, using age and gender as post-stratification variables, thus obtaining more reliable estimation of prevalence and lethality. Specifically, for Italy, we obtain a prevalence of 9%. The proposed methodology represents a reasonable approximation while waiting for more reliable data obtained with a properly designed national sample survey and that it could be further improved if more data were made available.

Frequency and severity of dental caries in foster care children of Turin, Italy: a retrospective cohort study.

AIM: Aim of this retrospective cohort study was to assess the frequency and severity of dental caries (DC) among foster care children in the city of Turin, in North West Italy, and to compare these data with those of a general paediatric population. MATERIALS AND METHODS: From May 2016 to September 2018, 75 paediatric subjects between the age of 4 and 12, located in 11 residential child care communities were recruited. Instructions were provided concerning oral health, caries and correlation with dietary habits. Oral and dental examination were carried out to establish frequency and severity of caries (not-penetrating, nPC, corresponding to the International Caries Detection and Assessment System (ICDAS) codes: 1-4, vs. penetrating, PC, corresponding to ICDAS codes: 5-6). Decayed, missed, filled teeth (DMFT) index was used. Data for comparison were acquired from the WHO Collaboration Center For Epidemiology and Community Dentistry of Milan (WHO-CCOMS), belonging to a nationwide sample of 2,141 Italian children. RESULTS: Only 13 subjects (17%) were caries-free; 187 caries were identified: 133 were PC, whereas 54 were nPC. Overall, 76% of the caries were found in deciduous teeth. Mean DMFT was 3.43 (D = 2.97; M = 0.24; F = 0.22). When the study data were compared to those from WHO-CCOMS, a significantly higher DMFT (3.43 vs 0.96; p <0.00001) and D (2.97 vs 0.62; p <0.00001) was detected. CONCLUSION: A significant higher frequency of caries in foster care children in Turin, Italy compared to the general population was detected.

The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast.

Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive. Results: Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). Conclusion: TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.

Radiation hybrid QTL mapping of Tdes2 involved in the first meiotic division of wheat.

Since the dawn of wheat cytogenetics, chromosome 3B has been known to harbor a gene(s) that, when removed, causes chromosome desynapsis and gametic sterility. The lack of natural genetic diversity for this gene(s) has prevented any attempt to fine map and further characterize it. Here, gamma radiation treatment was used to create artificial diversity for this locus. A total of 696 radiation hybrid lines were genotyped with a custom mini array of 140 DArT markers, selected to evenly span the whole 3B chromosome. The resulting map spanned 2,852 centi Ray with a calculated resolution of 0.384 Mb. Phenotyping for the occurrence of meiotic desynapsis was conducted by measuring the level of gametic sterility as seeds produced per spikelet and pollen viability at booting. Composite interval mapping revealed a single QTL with LOD of 16.2 and r (2) of 25.6 % between markers wmc326 and wPt-8983 on the long arm of chromosome 3B. By independent analysis, the location of the QTL was confirmed to be within the deletion bin 3BL7-0.63-1.00 and to correspond to a single gene located ~1.4 Mb away from wPt-8983. The meiotic behavior of lines lacking this gene was characterized cytogenetically to reveal striking similarities with mutants for the dy locus, located on the syntenic chromosome 3 of maize. This represents the first example to date of employing radiation hybrids for QTL analysis. The success achieved by this approach provides an ideal starting point for the final cloning of this interesting gene involved in meiosis of cereals.

Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype.

BACKGROUND: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer. METHODS: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007. RESULTS: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥ 14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33-0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27-0.95)). CONCLUSION: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.

Objective assessment of mandibular motor control using a 'reach-and-hold' task.

Mandibular motor function is well known to be impaired in the presence of temporomandibular disorders. However, while a vast literature is available concerning accuracy of motor control in limbs, quantitative and objective assessment of mandibular motor control has been seldom performed, also because of the lack of adequate investigative tools. Aim of this work is to present a technique for reliable evaluation of the motor performance of the mandible based on a kinesiography-monitored reach-and-hold task. Nineteen healthy subjects were engaged in a task in which they had to drive a cursor on a screen by corresponding movements of the mandible in the frontal plane and reach 30 random targets sequentially displayed on the screen. The whole task was repeated three times per session in two different days. The individual performance was assessed by different indices evaluating precision and steadiness of target matching. The performance progressively improved in the three trials of the first session, further improved and stabilised in the second session, with an average positioning error of 0·59 ± 038 mm and was slightly correlated with the horizontal dimension of the mandible border movement (r = 0·55). Intraclass correlation coefficient ranged between 0·76 and 0·94 for the different indices indicating good repeatability. The kinesiographic technique allowed for objective and reliable assessment of the voluntary control of the mandible position. Its potential applications include support to the characterisation of temporomandibular disorders and to motor training and progress monitoring in rehabilitation treatments.

Low-dose tamoxifen in the treatment of breast ductal intraepithelial neoplasia: results of a large observational study.

BACKGROUND: Tamoxifen's cost-benefit ratio for breast ductal intraepithelial neoplasia (DIN) is unclear. Since low-dose tamoxifen showed a favorable modulation of breast cancer biomarkers in phase II trials, a monoinstitutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment was analyzed. PATIENTS AND METHODS: A total of 309 patients with DIN received low-dose tamoxifen as part of institutional guidelines and were compared with 371 patients with DIN who received no systemic treatment after surgery. RESULTS: Women with estrogen receptor (ER)/progesterone receptor (PgR) >50% DIN who were not treated had a higher incidence of breast events than women on tamoxifen [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00-3.12] or women with ER/PgR <50% DIN (HR 1.72; 95% CI 1.14-2.58). Among untreated patients with ER >50% DIN, recurrence was higher in PgR > or =50% DIN than in PgR <50% DIN, whereas it was similar among low PgR (<50%) DIN against which tamoxifen had no effect. No difference in endometrial cancer incidence was noted. CONCLUSIONS: High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN, and low-dose tamoxifen appears to be an active treatment. Women with low-expression ER or PgR DIN do not seem to benefit from tamoxifen. A definitive clinical trial is warranted.

[Conservative approach for breast cancer. The experience of the European Institute of Oncology]. / L'approccio conservativo al carcinoma mammario.L'esperienza dell'Istituto Europeo di Oncologia.

Conservative surgery represents the standard care for patients with early breast cancer. The aim of this review was to discuss the extension of conservative surgery in controversial fields such as after primary chemotherapy for large tumours or the possibility to repeat conservative surgery for a local reappearance. The project of a conservative approach to breast cancers continues with sentinel node biopsy which is worldwide performed more and more frequently. In our institute sentinel node biopsy is the standard procedure in the axillary staging of breast cancer even in those clinical scenarios which were previously considered either controversial or a contraindication such as in multicentric breast cancer, during pregnancy, in intra-ductal neoplasias, after primary chemotherapy, and male breast cancer. This conservative approach is completed by the possibility to deliver a partial breast irradiation and to provide patients with more personalized adjuvant treatments tailored on the biological features of the tumour.

Transmigrated intrauterine device discovered 17 years after its insertion.

We present the case of an intraperitoneal IUD incidentally noted on lumbar spine X-rays and confirmed by CT. This was secondary to asymptomatic uterine perforation occurred at the time of insertion 17 years before.

Development of glass-ceramic scaffolds for bone tissue engineering: characterisation, proliferation of human osteoblasts and nodule formation.

Glass-ceramic macroporous scaffolds for tissue engineering have been developed using a polyurethane sponge template and bioactive glass powders. The starting glass (CEL2) belongs to the system SiO(2)-P(2)O(5)-CaO-MgO-Na(2)O-K(2)O and has been synthesised by a conventional melting-quenching route. A slurry of CEL2 powder, polyvinyl alcohol and water has been prepared in order to coat, by impregnation, the polymeric template. An optimised thermal treatment was then use to remove the sponge and to sinter the glass powders, leading to a glass-ceramic replica of the template. Morphological observations, image analyses, mechanical tests and in vitro tests showed that the obtained devices are good candidates as scaffolds for bone-tissue engineering, in terms of pore-size distribution, pore interconnection, surface roughness, and both bioactivity and biocompatibility. In particular, a human osteoblast cell line (MG-63) seeded onto the scaffold after a standardised preconditioning route in simulated body fluid showed a high degree of cell proliferation and a good ability to produce calcium nodules. The obtained results were enhanced by the addition of bone morphogenetic proteins after cell seeding.

[Human biobank in uro-oncological research].

PURPOSE. Uro-oncological translational research requires clinical data and human biological tissues collected within a biological tissue bank (BTB). We are hereby outlining ethic-legal, methodological and technical issues of a BTB establishment process, focusing particularly on prostate cancer and Italian setting. MATERIALS AND METHODS. Review of literature data, and national and international regulations and guidelines; direct field experience of urological BTB; counseling of the different professionals involved. RESULTS. Within a BTB establishment process, it is of utmost importance to protect the donors' privacy and rights through the programmatic adoption of the following procedures: 1) informed consent; 2) confidentiality protection thanks to anonymity of biological specimens and use of an "honest broker" method; 3) identification of a single responsible researcher; 4) dedicated and protected location; 5) approval of the Ethical Committee. There are two main organizational models of BTB: "systematic", i.e. collecting specimens from all patients and through the same methodology; "project-driven", i.e. prospectively selecting patients for a specific study and using the specific methods required by researchers. In the preliminary step it is necessary to establish detailed protocols of sampling and crioconservation techniques, and methods of validation and quality control. For prostate tissue sampling, several techniques have been described such as specimens of alternate slices, macro dissection, Tru-Cut. CONCLUSIONS. Today BTBs are necessary in order to support molecular and translational research in uro-oncology, and to overcome the limits of the research based only on clinicalpathological data. Ethic-legal and methodological issues related to BTBs are still requiring specific legislation and standardization of techniques.

Internal adaptation of fixed prosthodontics at shoulder preparation level evaluated by horizontal sections.

AIM: The precision of fixed prosthodontic restorations is fundamental for clinical success: well-fitting crowns reduce the risk of recurrent caries and periodontal disease. The aim of this study is to evaluate the internal fit of fixed prosthodontics at the shoulder preparation level by examining horizontal sections. METHODS: Twenty-four extracted teeth were resin-embedded and prepared on the platform of an iso-parallelometer with a 90 degrees shoulder with a rounded internal angle. Auro Galva Crown (AGC) copings were cemented in place. The preparations were observed by 3 different assessors at 8 points, first externally and then internally at 2 levels by grinding the specimen perpendicular to the long axis at 0.5 mm and at 0.2 mm from the margin of the preparation. A correction factor was calculated to derive real values from measured values. The results were analyzed using a linear regression with robust standard errors, accounting for within-subject correlation introduced by multiple measurements. Shrout-Fleiss Intraclass Correlation Coefficient (ICC) for Inter-Rater Reliability were calculated at each stage. RESULTS: Internal measurements at 0.5 and 0.2 mm from the margin provided data similar to the external margin data. Average inter-assessor differences were in the range of 2 mm. ICC ranged from 0.93 for the 0.5 mm level to 0.97 for the external level. CONCLUSIONS: External measurements effectively predict the internal precision at the shoulder level. Horizontal perimarginal sections allow the fit to be studied through the evaluation of a great number of points. Traditional vertical sections for the evaluation of internal fit enable only a few points to be observed. This internal observation method may be suitable for testing new materials.

Inhibition of phospholipase A2 activity reduces membrane fluidity in rat hippocampus.

Phospholipase A2 (PLA2) is a family of key enzymes in membrane phospholipid metabolism. In rats, the inhibition of PLA2 activity in the hippocampus was found to impair memory formation. Because memory function is largely dependent on the fluidity of brain membranes, we performed the present study to investigate the effects of in vivo PLA2 inhibition (with PACOCF3) on the fluidity of hippocampal membranes from rats trained in a learning task. Hippocampal tissue from rats injected with 100 microM PACOCF3 showed reduced membrane fluidity as compared to vehicle (p < 0.01), and the reduction of membrane fluidity was highly correlated with PLA2 inhibition (r = .76, p < 0.03). This finding is of interest because reduction of brain membrane fluidity impairs memory formation and both decreased PLA2 activity and reduced membrane fluidity have been reported in the brain from patients with Alzheimer's disease.

Diagnostic dilemmas in biliary strictures mimicking cholangiocarcinoma.

BACKGROUND/AIMS: Bile duct strictures may be malignant or benign. In the absence of previous biliary surgery a precise preoperative diagnosis is often difficult, in particular when a tumor mass is absent in the preoperative radiologic findings. METHODOLOGY: A review of 179 patients observed between 1982 and 2001 by the same surgical team with a preoperative diagnosis of malignant stricture of the biliary tree. A surgical procedure was performed in 153 of these cases. RESULTS: The presence of a malignant stricture was confirmed by final pathologic examination in 32 of 38 cases (96%) in which a curative resection was performed. A final diagnosis of inflammatory stricture secondary to choledocholithiasis was made in 3 of the remaining 6 cases (4%), along with one case each of sclerosing cholangitis, granular cell tumor and Mirizzi's syndrome, respectively. CONCLUSIONS: Precise preoperative evaluation of biliary structures can be very difficult when a tumor mass is absent. Despite the use of invasive procedures and new techniques such as magnetic resonance cholangiopancreatography, a false-positive rate of 4% may be expected. However, whenever a malignancy is not definitely excluded, biliary strictures should be treated as a cholangiocarcinoma.

Three-dimensional CT imaging and virtual endoscopy for the placement of self-expandable stents in oesophageal and tracheobronchial neoplastic stenoses.

We examined the value of multislice computed tomography (CT) with three-dimensional (3D) reconstruction of the images as a pre-treatment examination in order to plan endoluminal stenting in 14 patients with large tumours involving the oesophagus and/or the tracheobronchial tree. The measurement of the stenosis obtained during 3D reconstruction of the CT images corresponded to that obtained by endoscopy and to the prosthesis chosen in all cases, with the exception of one patient undergoing double stenting due to inadequate gaseous distension of the oesophageal lumen. 3D CT may add information with respect to axial imaging, and be helpful to better plan and perform stenting of the oesophagus and airways without burdening the preoperative work-up.