Endocannabinoid system expression in ovarian epithelial tumors according to the dualistic model of ovarian carcinogenesis.

OBJECTIVE: Our study aimed to confirm the expression of the endocannabinoid system in the human epithelial ovarian tumors, assessing the immunohistochemical expression of Cannabinoid Receptor Type 1 and Fatty Acid Amide Hydrolase in benign, borderline and malignant tumors. MATERIALS AND METHODS: Cannabinoid Receptor Type 1 and Fatty Acid Amide Hydrolase immunohistochemical expression was determined in 118 epithelial ovarian tumors sequentially treated during the last decade in our department: 36 benign, 34 borderline and 48 malignant neoplasms. Cannabinoid Receptor type 1 and Fatty Acid Amide Hydrolase expression resulted predominantly weak-moderate in the benign and borderline forms. RESULTS: concerning malignant tumors, Cannabinoid Receptor Type 1 expression resulted predominantly moderate-strong in Type I tumors and negative-weak in Type II tumors. Fatty Acid Amide Hydrolase expression resulted, instead, independent by the tumor types. Furthermore, there was no significant difference in the Cannabinoid Receptor Type 1 and Fatty Acid Amide Hydrolase expression relatively to the tumoral stages. CONCLUSIONS: The present study confirmed a variable expression of the endocannabinoid system in human ovarian tumors. Cannabinoid Receptor Type 1 expression was significantly different in malignant epithelial ovarian tumors according to dualistic model of ovarian carcinogenesis. Thus, in the most aggressive types II ovarian tumors, Cannabinoid Receptor Type 1 expression resulted predominantly negative or weak.

Prophylactic sublay non-absorbable mesh positioning following midline laparotomy in a clean-contaminated field: randomized clinical trial (PROMETHEUS).

BACKGROUND: Incisional hernia is a frequent postoperative complication after midline laparotomy. Prophylactic mesh augmentation in abdominal wall closure after elective surgery is recommended, but its role in emergency surgery is less well defined. METHODS: This prospective randomized trial evaluated the incidence of incisional hernia in patients undergoing urgent midline laparotomy for clean-contaminated surgery. Closure using a slowly absorbable running suture was compared with closure using an additional sublay mesh (Parietex ProGrip™). Patients were randomized just before abdominal wall closure using computer-generated permuted blocks. Patients, care providers, staff collecting data, and those assessing the endpoints were all blinded to the group allocation. Patients were followed up for 24 months by means of clinical and ultrasonographic evaluations. RESULTS: From January 2015 to June 2018, 200 patients were randomized: 100 to primary closure (control group) and 100 to Parietex ProGrip™ mesh-supported closure (mesh group). Eight patients in the control group and six in the mesh group were lost to follow-up. By 24 months after surgery, 21 patients in the control group and six in the mesh group had developed incisional hernia (P = 0.002). There was no difference between groups in the incidence of haematoma (2 versus 5; P = 0.248) and superficial wound infection (4 versus 5; P = 0.733). Multivariable analysis confirmed the role of mesh in preventing incisional hernia (odds ratio 0.11, 95 per cent c.i. 0.03 to 0.37; P < 0.001). One patient in the mesh group required mesh removal because of deep infection. CONCLUSION: Prophylactic mesh-augmented abdominal wall closure after urgent laparotomy in clean-contaminated wounds is safe and effective in reducing the incidence of incisional hernia. Registration number: NCT04436887 (http://www.clinicaltrials.gov).

Intestinal, intestinal-type and intestine-localized metastatic adenocarcinoma. Immunohistochemical approach to the differential diagnosis.

The pathologist is often called to define the origin of tumors through the help of ancillary studies, mainly immunohistochemical stainings. In this setting, the differential diagnosis between intestinal adenocarcinomas, other tumors with intestinal-type morphology, and adenocarcinomas metastatic to the bowel can be particularly difficult. In such cases, an accurate assessment of the disease is required to address the patients to the optimal treatment. Immunohistochemistry offers the use of multiple antibodies: the integrated evaluation of specific stainings can lead to a correct diagnosis. Particularly, the use of cytokeratins, mucins, and ß-catenin could be of great help in most cases. In addition, recently, novel specific markers such as SATB2 and AMACR have been introduced, improving the utility of immunohistochemistry in the differential diagnosis of intestinal-type and intestinal adenocarcinomas.

Molecular pathways triggered by COVID-19 in different organs: ACE2 receptor-expressing cells under attack? A review.

OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.

Management of the mother-infant dyad with suspected or confirmed SARS-CoV-2 infection in a highly epidemic context.

In the context of SARS-CoV-2 pandemic, the hospital management of mother-infant pairs poses to obstetricians and neonatologists previously unmet challenges. In Lombardy, Northern Italy, 59 maternity wards networked to organise the medical assistance of mothers and neonates with suspected or confirmed SARS-CoV-2 infection. Six "COVID-19 maternity centres" were identified, the architecture and activity of obstetric and neonatal wards of each centre was reorganised, and common assistance protocols for the management of suspected and proven cases were formulated. Here, we present the key features of this reorganization effort, and our current management of the mother-infant dyad before and after birth, including our approach to rooming-in practice, breastfeeding and neonatal follow-up, based on the currently available scientific evidence. Considered the rapid diffusion of COVID-19 all over the world, we believe that preparedness is fundamental to assist mother-infant dyads, minimising the risk of propagation of the infection through maternity and neonatal wards.

The potential diagnostic and predictive role of anaplastic lymphoma kinase (ALK) gene alterations in melanocytic tumors.

OBJECTIVE: Anaplastic lymphoma kinase (ALK) gene has been demonstrated to be rearranged, mutated or amplified in several haematological and solid tumors. Moreover, the use of ALK inhibitors has recently revolutionized the treatment of ALK-rearranged patients affected by non-small cell lung carcinoma. Herein we review the genetic alterations of ALK in melanocytic neoplasms described in literature, focusing on their potential diagnostic and predictive role. MATERIALS AND METHODS: The Authors reviewed the pertinent literature through research on PubMed server was performed typing the terms "ALK", "Anaplastic lymphoma kinase", "ALKATI", "Melanoma", "Spitz", "Spitzoid". RESULTS: ALK translocations were demonstrated in melanocytic neoplasms, particularly in acral melanoma and spitzoid tumors. ALKATI was described in primary and metastatic melanoma, indicating its early occurrence in oncogenesis, with varying immunohistochemical expression of the protein. CONCLUSIONS: The identification of the specific type of ALK mutations could be interesting for planning biologic therapy of melanoma patients. Further studies are needed to evaluate the possibility to introduce an ALK-targeted therapy in patients affected by malignant melanoma.

Melanin bleaching with potassium permanganate for melanocytic lesions diagnosis in veterinary medicine / Despigmentação de melanócitos com permanganato de potássio para diagnóstico de lesões melanocíticas na medicina veterinária

The aim of this study was to microscopically re-evaluate the melanocytic lesions diagnoses established by the Animal Pathology Laboratory of the Federal University of Uberlândia, in the state of Minas Gerais, Brazil, over a period of eleven years; in addition, to perform a comparative analysis between the conventional histopathological (CH) method and the use of the melanin bleaching (MB) technique with potassium permanganate, sulfuric acid, and oxalic acid solutions. The results of the MB method presented a disagreement in 24.32% of the diagnosis previously by CH, with low agreement (61.0%) and low Kappa coefficient (0.2267). Melanoma was the most frequent lesion, more frequent in elderly and non-breed female dogs. The most frequent melanoma location was in the cutaneous tissue. The presence or absence of a pagetoid spread in cutaneous samples, distribution of melanin, pattern of cell layout, cell morphology, degree of cellular atypia, and the number of mitoses verified after MB were the most important criteria to confirm the diagnosis of malignancy or benignity of the lesions. Evaluating pathologists considered MB to be essential for the majority of diagnoses and an efficient complementary method for the diagnosis of melanocytic lesions, even in cases with a moderate degree of pigmentation.(AU)

Este estudo objetivou reavaliar microscopicamente os diagnósticos de lesões melanocíticas estabelecidos pelo setor de Patologia Animal da Universidade Federal de Uberlândia, em um período de 11 anos, e, com base nesse levantamento, realizar uma análise comparativa entre o método histopatológico convencional (HC) e o método de despigmentação de melanócitos (DM) com permanganato de potássio, ácido sulfúrico e ácido oxálico. A DM revelou discordância em 24,32% dos diagnósticos previamente estabelecidos por HC, apresentando baixa concordância (61,0%) e baixo valor de coeficiente Kappa (0,2267). A alteração mais frequente foi o melanoma, com maior ocorrência em cadelas idosas sem raça definida (SRD). A localização mais frequente dos melanomas foi cutânea. A presença ou ausência de disseminação pagetoide nos casos cutâneos, a forma de distribuição da melanina, o padrão de disposição das células, a morfologia celular, o grau de atipia celular e a quantidade de mitoses verificada após a despigmentação foram critérios de elevada importância para firmar o diagnóstico quanto à malignidade ou benignidade da lesão. A despigmentação foi considerada pelos patologistas avaliadores como essencial para o diagnóstico na maioria dos casos, o que leva a concluir que ela constitui um método complementar eficiente no diagnóstico das lesões melanocíticas, mesmo em casos com grau moderado de pigmentação.(AU)

Quasi-thresholdless Photon Upconversion in Metal-Organic Framework Nanocrystals.

Photon upconversion based on sensitized triplet-triplet annihilation ( sTTA) is considered as a promising strategy for the development of light-managing materials aimed to enhance the performance of solar devices by recovering unused low-energy photons. Here, we demonstrate that, thanks to the fast diffusion of excitons, the creation of triplet pairs in metal-organic framework nanocrystals ( nMOFs) with size smaller than the exciton diffusion length implies a 100% TTA yield regardless of the illumination condition. This makes each nMOF a thresholdless, single-unit annihilator. We develop a kinetic model for describing the upconversion dynamics in a nanocrystals ensemble, which allows us to define the threshold excitation intensity  Ithbox required to reach the maximum conversion yield. For materials based on thresholdless annihilators, Ithbox is determined by the statistical distribution of the excitation energy among nanocrystals. The model is validated by fabricating a nanocomposite material based on nMOFs, which shows efficient upconversion under a few percent of solar irradiance, matching the requirements of real life solar technologies. The statistical analysis reproduces the experimental findings, and represents a general tool for predicting the optimal compromise between dimensions and concentration of nMOFs with a given crystalline structure that minimizes the irradiance at which the system starts to fully operate.

Diagnosis of anaplastic large cell lymphoma on late peri-implant breast seroma: Management of cytological sample by an integrated approach.

INTRODUCTION: Peri-implant breast seroma is a late clinical presentation of reconstructive surgery or augmentation mammoplasty with breast implants. Pre-operative cytological evaluation of the peri-implant breast seroma is a common clinical approach, showing mainly an inflammatory reaction or more rarely a breast implant-associated anaplastic large cell lymphoma. Herein, we reported the role of cytology in the evaluation of peri-implant breast seroma and its critical pre-operative implications. METHODS: Eight cases of peri-implant breast seroma from files at Luigi Vanvitelli University were identified between January and December 2017. In all cases, seroma was aspirated; cytospins were performed and stained by Papanicolaou stain; finally, in all cases, a cell block was obtained for immunocytochemical evaluation and, in one case, for FISH to detect ALK1-gene translocation. RESULTS: The median age of patients was 48 years and the mean time between the implant placement and the occurrence of peri-implant breast seroma was 18 months. Microscopic examination showed breast implant-associated anaplastic large cell lymphoma in one case, aspecific inflammatory reaction in six cases and silicon-associated reaction in one case. CONCLUSIONS: Peri-implant breast seroma may be caused by several pathological conditions with different clinical behaviour. A proper cytological approach to peri-implant breast seroma allows a correct differential diagnosis between inflammatory conditions and breast implant-associated anaplastic large cell lymphoma and an appropriate management of the patient.

Prognostic Value of Occult Isolated Tumour Cells within Regional Lymph Nodes of Dogs with Malignant Mammary Tumours.

Canine mammary tumours (CMTs) are the most common type of neoplasm in bitches. As in women, the presence of metastasis in regional lymph nodes is an important prognostic factor in bitches with mammary carcinomas, but the clinical significance of occult isolated tumour cells (ITCs) within lymph nodes is still undefined in this species. The effectiveness of immunohistochemistry (IHC) in identifying occult ITCs and micrometastasis (MIC) was compared with that of the conventional haematoxylin and eosin staining technique. The relationship between tumour size, histological type, histological grade and the presence of metastasis was evaluated. The overall survival (OS) of female dogs with occult mammary carcinomas and ITCs within lymph nodes was analysed. Fragments of mammary carcinoma and regional lymph nodes of 59 female dogs were also evaluated. Histological sections of mammary carcinoma and lymph node samples were studied for tumour diagnosis and lymph node samples were tested by IHC using a pan-cytokeratin antibody. It was found that 35.2% of occult ITCs and 2.8% of hidden MIC were detected when IHC was used. There was a good correlation between the size of the tumour and metastasis to the lymph nodes (P = 0.77). ITCs were observed more frequently in the medullary region (60.7%) and metastases in the cortical region (44.4%). There was no significant difference in the OS between female dogs with occult ITCs and lymph nodes without ITCs. IHC can detect occult tumour cells in lymph nodes that are negative by histopathological examination. Female dogs with nodal ITCs do not have lower survival.

Mottness at finite doping and charge-instabilities in cuprates.

The influence of the Mott physics on the doping-temperature phase diagram of copper oxides represents a major issue that is subject of intense theoretical and experimental effort. Here, we investigate the ultrafast electron dynamics in prototypical single-layer Bi-based cuprates at the energy scale of the O-2p→Cu-3d charge-transfer (CT) process. We demonstrate a clear evolution of the CT excitations from incoherent and localized, as in a Mott insulator, to coherent and delocalized, as in a conventional metal. This reorganization of the high-energy degrees of freedom occurs at the critical doping pcr ≈0.16 irrespective of the temperature, and it can be well described by dynamical mean field theory calculations. We argue that the onset of the low-temperature charge instabilities is the low-energy manifestation of the underlying Mottness that characterizes the p < pcr region of the phase diagram. This discovery sets a new framework for theories of charge order and low-temperature phases in underdoped copper oxides.

Epithelioid angiosarcoma arising in schwannoma of the kidney: report of the first case and review of the literature.

BACKGROUND: Schwannoma and angiosarcoma are infrequent pathologies that have been rarely reported in the kidney. Angiosarcoma is an uncommon malignant tumor presenting a recognizable vascular differentiation. It can develop in any site but the most common locations include the skin, soft tissues, breast, bone, liver, and spleen while renal localization has been very rarely reported in the literature. Schwannoma is a benign peripheral nerve sheath tumor composed of cells with the immunophenotype and ultrastructural features of differentiated Schwann cells. It has a wide anatomical distribution but the most frequent locations include subcutaneous tissues of the extremities and the head and neck region and the retroperitoneal and mediastinal soft tissues. The occurrence of an angiosarcoma in a pre-existing schwannoma is an extremely rare event with <20 cases reported in worldwide literature. In the present study, a renal case of angiosarcoma arising in schwannoma is presented with a detailed review of the pertinent literature. CASE PRESENTATION: A 56-year-old man was admitted with a few days history of lower back pain and hematuria. Abdominal ultrasound showed a mass inside the left renal medulla. Subsequent imaging investigations with computed tomography and magnetic resonance confirmed the presence of the lesion and showed a pulmonary metastasis. CONCLUSIONS: The final histopathological examination led to the diagnosis of epithelioid angiosarcoma arising in a schwannoma. The patient came to death a few months later due to a massive hemothorax. To the best of our knowledge, the present is the first case of an angiosarcoma arising in a schwannoma of the kidney.