The Histopathological Growth Pattern of Colorectal Liver Metastases Impacts Local Recurrence Risk and the Adequate Width of the Surgical Margin.

BACKGROUND: The histopathological growth pattern (HGP) of colorectal liver metastases (CLM) has been associated with prognosis. This study was designed to elucidate if the HGP is associated with local recurrence risk and impacts the adequate width of surgical margin. METHODS: All consecutive patients resected for CLM in 2018-2019 were considered. HGP was prospectively classified as follows: desmoplastic, pushing, and replacement. Surgical margin was classified as follows: R0 (margin ≥ 1 mm), R1vasc (0-mm margin, tumor detachment from intrahepatic vessels), and R1par (tumor exposure along transection plane). R0 resections were further distinguished in R0min (1-mm margin) and R0wide (> 1-mm margin). RESULTS: A total of 340 resection areas in 136 patients were analyzed (70 R0min, 143 R0wide, 31 R1vasc, 96 R1par). HGP was desmoplastic in 26 cases, pushing in 221, and replacement in 93. Thirty-six local recurrences occurred (11%, median follow-up 21 months): 1 after R0wide, 4 after R0min, 3 after R1vasc, and 28 after R1par resection. In R1par group, local recurrence rate was high independently of HGP (29%). In R1vasc and R0min groups, local recurrence risk was higher in the replacement group (R1vasc: 29% vs. 4% if pushing/desmoplastic; R0min: 11% vs. 4%). In R0wide group, local recurrence risk was low for all HGP ( < 1%). Independent predictors of local recurrence were replacement HGP (odds ratio = 1.654, P = 0.036), and R1par resection (odds ratio = 57.209, P < 0.001 vs. R0). CONCLUSIONS: Replacement HGP is associated with an increased risk of local recurrence. In these patients, a wide surgical margin should be pursued, because R1vasc and R0min resections could be insufficient. R1par resection is inadequate, independently of the HGP.

Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM).

The Italian Association of Medical Oncology recommendations on thymic epithelial tumors, which have been drawn up for the first time in 2020 through an evidence-based approach, report indications on all the main aspects of clinical management of this group of rare diseases, from diagnosis and staging, to new available systemic treatments, such as targeted therapies and immunotherapies. A summary of key recommendations is presented here and complete recommendations are reported as Supplementary Materials, available at https://doi.org/10.1016/j.esmoop.2021.100188.

[18F]FDG-PET/CT texture analysis in thyroid incidentalomas: preliminary results.

BACKGROUND: significance of incidental thyroid 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans remains controversial. We aimed to evaluate the ability of [18F]FDG-PET/CT texture analysis to predict final diagnosis in thyroid incidentaloma. METHODS: We retrospectively evaluated medical records of all patients who performed a [18F]FDG-PET/CT from January 2012 to October 2016. Those patients who presented a thyroid incidentaloma described in the medical records and performed a fine needle aspiration in our institution were considered for the analysis. Cytological and/or histological results were used as reference standard to define the final diagnosis. In case of negative cytology, the nodule was considered benign. In case of non-diagnostic or inconclusive results ultrasound, follow-up and further cytology/histology were used as final diagnosis. For suspected or positive cytological result, histology was used as reference standard. PET images were segmented using a General Electric AW workstation running PET VCAR software (GE Healthcare, Waukesha, WI, USA) settled with a threshold of 40% SUVmax. LifeX software (http://www.lifexsoft.org) was used to perform texture analysis. Statistical analysis was performed with R package (https://www.r-project.org). RESULTS: We identified 55 patients with incidental thyroid [18F]FDG uptake. Five patients were excluded from the analysis because a final diagnosis was not available. Thirty-two out of 50 patients had benign nodules while in 18/50 cases a malignancy (primary thyroid cancer = 15, metastases = 3) was diagnosed. Conventional PET parameters and histogram-based features were calculated for all 50 patients, while other matrices-based features were available for 28/50 patients. SUVmax and skewness resulted significantly different in benign and malignant nodules (p = 0.01 and = 0.02, respectively). Using ROC analysis, seven features were identified as potential predictors. Among all the textural features tested, skewness showed the best area under the curve (= 0.66). SUV-based parameters resulted in the highest specificity while MTV, TLG, skewness and kurtosis, as well as correlationGLCM resulted better in sensitivity. CONCLUSIONS: [18F]FDG-PET/CT texture analysis seems to be a promising approach to stratify the patients with thyroid incidentaloma identified on PET scans, with respect to the risk of the diagnosis of a malignant thyroid nodule and thus, could refine the selection of the patients to be referred for cytology.

[A new human machine interface in neurosurgery: The Leap Motion(®). Technical note regarding a new touchless interface]. / Un nouvel interface homme machine en neurochirurgie : le Leap Motion(®). Note technique sur une nouvelle interface homme machine sans contact.

Currently, cross-sectional imaging viewing is used in routine practice whereas the surgical procedure requires physical contact with an interface (mouse or touch-sensitive screen). This type of contact results in a risk of lack of aseptic control and causes loss of time. The recent appearance of devices such as the Leap Motion(®) (Leap Motion society, San Francisco, USA) a sensor which enables to interact with the computer without any physical contact is of major interest in the field of surgery. However, its configuration and ergonomics produce key challenges in order to adapt to the practitioner's requirements, the imaging software as well as the surgical environment. This article aims to suggest an easy configuration of the Leap Motion(®) in neurosurgery on a PC for an optimized utilization with Carestream(®) Vue PACS v11.3.4 (Carestream Health, Inc., Rochester, USA) using a plug-in (to download at: https://drive.google.com/?usp=chrome_app#folders/0B_F4eBeBQc3ybElEeEhqME5DQkU) and a video tutorial (https://www.youtube.com/watch?v=yVPTgxg-SIk).

Comparative molecular analysis of bacterial species associated with periodontal disease.

Periodontal disease is an inflammatory disorder affecting the supporting teeth structures, including gingiva, periodontal ligament and alveolar bone, causing loss of connective tissue, reabsorption of alveolar bone and formation of periodontal pockets. The aim of this study is to find a correlation between bacterial growth and periodontal disease. Fifty-seven patients aged between 21 and 65 years, median age 46 years, were enrolled. According to gingival pocket depth, ranging from 3 to 7 mm, patients were divided into two groups: the first (30 patients, 53%) with deep pockets ³ 5 mm and the second (27 patients, 47%) less than 5 mm. The samples taken were processed for microbiological analysis by absolute quantitative real-time Taq-Man technique. Patients affected by periodontal disease were 32 (56%) and patients with gingival bleeding were 35 (61%). This data showed that the presence, the type and the bacterial load in gingival pockets were strongly correlated with gingival depth, periodontal disease and gingival bleeding. Quantitative microbiological analysis is a key point to improve patient compliance, allowing to choose the specific antibiotic treatment. avoiding antibiotic resistance and ensuring the successful outcome of therapy for periodontal disease.

Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review.

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were 'HBV therapy', 'HBV treatment', 'VE antiviral effects', 'tocopherol antiviral activity', 'miRNA antiviral activity' and 'VE microRNA'. Reports describing the role of miRNA in the regulation of HBV life cycle, in vitro and in vivo available studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

Impact of capsaicin on mast cell inflammation.

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FcERI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism (such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4), histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

Systemic nickel allergy syndrome: nosologic framework and usefulness of diet regimen for diagnosis.

Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS). The objective of the study was to describe the nosologic framework of the syndrome and to compare sensibility and specificity for SNAS diagnosis between two different low nickel diets - BraMa-Ni and the usually prescribed list of forbidden foods - along with patient adherence to diet. One hundred forty-five patients with suspected SNAS (by history and benefit from nickel dietary restrictions) were selected and orally challenged with nickel for a definite diagnosis. Specificity and sensibility of the diets were calculated in relation to the results of nickel challenges. The nosologic framework of SNAS was deduced from the clinical pictures of 98 patients with positive nickel challenge and characterized essentially by skin and gastrointestinal symptoms, whereas all other symptoms (dizziness, headache etc.) were never elicited by the oral nickel challenge. The specificity and sensibility of BraMa-Ni in detecting SNAS were significantly higher than the forbidden food list diet, with an excellent patient adherence. Therefore, BraMa-Ni diet can be prescribed for the treatment of the syndrome other than for the diagnosis, the gold standard of which remains the oral nickel challenge.

Potential impact of the 70-gene signature in the choice of adjuvant systemic treatment for ER positive, HER2 negative tumors: a single institution experience.

PURPOSE: We investigated in a single institution series of 124 women with operable breast cancer whether tumor clinicopathological features could predict the 70-gene signature (Mammaprint, MP) results, and whether MP results could help to make decisions for the use of chemotherapy (CT) in patients (pts) with ER positive breast cancer beyond recommendations of international guidelines. RESULTS: Among the 68 ER/PgR positive, HER2 negative tumors, Ki-67 ≥ 20% was the only significant predictor of a high risk-MP among standard clinicopathological features. In candidates for endocrine therapy with undetermined benefit from CT according to international guidelines, MP results would have led to different treatment decisions in 13/46 (28%) and in 20/68 (29%) pts according to NCCN and St. Gallen recommendations, respectively. CONCLUSIONS: Ki-67 independently predicted high risk-MP in ER/PgR positive, HER2 negative tumors. MP results would have led to discordant treatment recommendations in about 30% of cases, generally increasing indication rate for CT. The results of large randomized trials are warranted in order to understand whether we should rely on multigene assays rather than on standard clinicopathological features for treatment decisions.

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

Reproducibility of the WHO classification of thymomas: practical implications.

BACKGROUND: The WHO-classification was shown to be an independent prognostic marker in some but not all retrospective studies possibly due to lack of reproducibility. We investigated the reproducibility of the WHO-classification and its prognostic implication using a large series of resected thymomas. METHODS: Four independent pathologists histologically classified a surgical series of 129 thymic tumors in a blinded fashion. Fleiss' kappa-coefficient was used to assess the pathologists' overall agreement, and Cohen-Kappa to assess the agreement between two observers. Disease-related-survival (DRS) and progression-free-survival (PFS) curves were generated by Kaplan-Meier method and compared by log-rank test. RESULTS: In 63/129 (48.8%) cases there was a complete agreement; in 43/129 (33.3%) cases 3/4 pathological diagnoses were identical; in 15/129 (11.6%) cases the diagnoses were identical by pair; in 8/129 (6.2%) cases three different pathological diagnoses were on record. The Kappa-correlation coefficient was only moderate (0.53). A following web review carried out on the 23 cases with at least two different diagnoses reached a complete consensus. The histotype showed a statistically significant impact on PFS and DRS in the classification provided by only two pathologists. CONCLUSIONS: In this study, the agreement on WHO classification of thymomas was only moderate and this impacted on patients management. Web consensus conference on the diagnosis, more stringent diagnostic criteria or the adoption of referral diagnostic centres may substantially reduce discrepancies.

Low-dose "metronomic chemotherapy" with oral cyclophosphamide and methotrexate in metastatic breast cancer: a case report of extraordinarily prolonged clinical benefit.

We report the case of a 34-year-old woman affected by breast cancer that had metastasized to the bone. She had been treated with oral cyclophosphamide and methotrexate (metronomic chemotherapy) and achieved 3.5 years of clinical remission. To our knowledge, this is the first description of such a prolonged response to therapy. This case report adds weight to known data on metronomic treatment and supports further investigation of this therapy.

A 3-D study of capsular invasion in follicular thyroid tumors. A novel approach to an old dilemma.

OBJECTIVE: The diagnosis of follicular tumors of the thyroid mainly rests on the examination of peri-lesional capsule. Lesions with an intact shell are labeled as adenoma, those with capsular invasion are considered carcinoma and those with doubtful aspects are regarded as tumors of uncertain malignant potential. AIM: To better understand the biology of capsular invasion and its practical implication by applying a peculiar three dimension (3-D) reconstruction. METHOD: Two follicular carcinoma (FC) and one follicular tumour of uncertain malignant potential (FT-UMP) were considered. Areas of true/doubtful capsular invasion were labeled using Tissue Micro Array technology and the corresponding paraffin blocks underwent serial sectioning. H&E slides (range 30-100, mean 70) were captured as pictures, aligned using automated method based on the maximization of mutual information and imported into a 3-D image processing software (AMIRA). RESULTS: The 3-D reconstruction revealed that capsular openings were oval shaped and sized approximately equal to 100-200 microm. In one FC the hole was entirely engaged by a tumor mass. In the remaining cases (1 FC and 1 FT-UMP) the 3-D reconstruction showed a small feeding vessel (approximately equal to 50 micro) passing through the capsule together with the bulge of the lesion [see 3-D reconstruction at http://www.ibfm. cnr.it/ricerca/inv_cap.php]. CONCLUSIONS: Our approach allows a better spatial reconstruction of the exact point of capsular interruption; the results obtained suggest that capsular invasion can be due either by abruptly interruption of the shell or by a protrusion along the path of a small feeding vessel.

[About a simple method to prevent accidents caused by changes in positioning in surgery: The transparent head drape]. / Le champ de tête transparent. Un moyen simple de prévention des accidents liés au changement d'installation en chirurgie plastique.

Surgical drapes are a physical barrier between the surgical team's sterile working space (the operating field) and the non-sterile environment of the anaesthesia team and the nursing team within the operating theatre. Once the patient's position has been checked and the skin preparation has been done, they are put in place. They are usually opaque, leaving visible just the areas where the surgical and anaesthesia teams will be working. When the patient's position is changed perioperatively, malpositions may be unnoticed and cause complications. Using a transparent head drape allows one to check the position of the head and upper limbs at all times, thus reducing the risk of complications. It is a simple, easy, economic, non-restrictive method which will produce an improvement in the quality of patient care.

Sinusal localization of nodal micrometastases is a prognostic factor in breast cancer.

BACKGROUND: Breast cancer micrometastases are frequently found during pathological examination of sentinel lymph nodes and complete axillary lymph node dissection. Despite this, their clinical relevance is still debated. The aim of this study is to investigate features that affect disease-free survival (DFS) and overall survival (OS) in patients with nodal micrometastases from breast cancer. MATERIAL AND METHODS: We retrospectively investigated the outcome of 122 patients with nodal micrometastases from breast cancer followed up for 60 months. RESULTS: At univariate analysis, worse DFS was related to features of primary tumor (multifocality P = 0.002; size >2 cm, P = 0.022; grade P = 0.022; absence of estrogen P < 0.001 and progesterone P < 0.001 receptors; HER-2 overexpression P = 0.006; vascular invasion P = 0.039; proliferative fraction > or =20% P = 0.034) and micrometastases (sinusal localization P = 0.010). Among the above-mentioned features, two were strongly associated with worse DFS in the multivariate model, i.e. negative receptorial status [hazard ratio (HR) = 11.24, 95% confidence interval (CI) 4.06-31.09; P < 0.001] and sinusal localization of micrometastasis (HR = 3.66, 1.18-11.36; P = 0.025). The OS was influenced by multifocality (P < 0.001) and receptor status (P = 0.005). CONCLUSION: Our results indicate that in patients affected by breast cancer, in addition to the well-known pathological features of primary tumor, sinusal localization of micrometastasis strongly impacts on the prognosis.

Outcome of T1N0M0 breast cancer in relation to St. Gallen risk assignment criteria for adjuvant therapy.

T1N0M0 (stage I) breast cancer (BC) has been increasing in recent decades but the optimal adjuvant approach remains controversial. To assess the outcome of BC patients stratified and treated with multimodal therapies according to St. Gallen consensus meeting recommendations, we retrospectively evaluated an unselected cohort of T1N0M0 BC patients, with respect to the St. Gallen criteria. At a median follow-up of 5 years, the recurrence rate, recurrence-free survival and overall survival were 7%, 94% and 96% respectively, and 60% of relapses were locoregional. No statistically significant difference was observed between T1a,b/T1c groups, or among risk categories (high/intermediate/low). The very low rate of distant recurrences even in patients with unfavorable prognostic factors seems to support the use of adjuvant systemic therapies but better prognostic and predictive factors are strongly needed for this subset of patients.

Combined endoscopic approach in the treatment of benign broncho-oesophageal fistula.

The treatment of benign broncho-oesophageal fistula is usually surgical but sometimes other methods of treatment are preferred. The case history is described of an adult in poor general condition in which an endoscopic approach combined with the use of fibrin glue on the bronchial side and metallic clips on the oesophageal side was used to close the fistula.

Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients.

The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation.

[Angiosarcoma of the nasal cavity. Report of a case and review of the literature]. / Angiosarcoma della cavità nasale. Descrizione di un caso e revisione della letteratura.

We report an unusual case of primary angiosarcoma of the nasal cavity (AS-nc). Clinical--monolateral epistaxis in a young person--, radiological--polypoid hemorrhagic tumor arising within the nasal cavity and expanding into paranasal sinuses--, pathological--a network of anastomosing channels and solid areas immunoreactive for CD31 and CD34--and prognostic features--patient alive and well 36 months after the original diagnosis--are superimposable to those of previously reported AS-nc, suggesting that this lesion should be considered as a peculiar variant of classical AS.