Total thyroidectomy associated to chemotherapy in primary squamous cell carcinoma of the thyroid

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant disease with rapid fatal prognosis. The onset is generally characterized by sudden bilateral latero-cervical lymphadenopathy. The Authors report patient of 58-year-old who referred for evaluation of rapidly aggravating bilateral latero-cervical lymphadenopathy. The US highlighted the presence of a hypoechoic nodular lesion characterized by peri and intra-nodular vascularization. Multilayer CT showed diffused involvement of mediastinal and bilateral latero-cervical lymph nodes, with no evidence of primary pulmonary neoplasia or elsewhere. The patient underwent total thyroidectomy. The peri-isthmic tissue was removed due to the presence of a small roundish formation, that was due to lymph node metastasis at histological examination. Histological diagnosis: PSCCT. The immunohistochemical panel of the thyroid lesion was indispensable for the differential diagnosis between PSCCT, medullary carcinoma, anaplastic carcinoma, and thyroid metastasis of neoplasia with unknown primitiveness. The patient underwent chemotherapeutic treatment with Carboplatin and Paclitaxel with modest improvement of dysphagia symptoms and reduction of 10-15% of the target lesions. The clinical course was characterized by loco-regional progression of the disease with exitus in 10 months after diagnosis. Survival and quality of life after surgical therapy and chemotherapy were like that of patients undergoing only chemotherapy. Due to the extreme rarity of the neoplasia, 60 cases described in Literature, no exclusive guidelines are reported for PSCCT. More extensive case studies are needed to evaluate the effects of total thyroidectomy with intent R0/R1 on improving survival and quality of life of patients with PSCCT

Acute pancreatitis secondary to non-functioning pancreatic neuroendocrine tumor: uncommon clinical presentation. Clinical case and review of literature

I tumori neuroendocrini del pancreas (PNET) sono rari, e rappresentano <5% di tutte le neoplasie pancreatiche, suddivisi in PNET funzionanti con secrezione ormonale responsabile di sintomi specifici e PNET non funzionanti (nf-PNET) generalmente di diagnosi tardiva per la comparsa di metastasi o manifestazioni cliniche per effetti compressivi. L’approccio chirurgico è il trattamento di scelta per PNETs funzionanti, non-funzionanti di diametro superiore a 2 cm o sintomatici per disturbi da compressione. Osservazione personale. Donna di 76 anni ricoverata presso la UOC-Università-Chirurgia Ospedale “A. Fiorini” di Terracina per nausea e dolore ai quadranti addominali superiori con irradiazione dorso-lombare, insorti dopo un pasto serale. Dopo gli esami ematochimici e le indagini strumentali, è stata fatta la diagnosi di pancreatite acuta severa. Gli US convenzionali, CCT, CE-MRI ed EUS hanno mostrato una lesione di 2,8 cm di diametro nella giunzione testa-corpo del pancreas. L’esame citologico FNA non ha rilevato la presenza di cellule pancreatiche atipiche. La scintigrafia total body con Octreoscan® ha documentato un’area di ipercaptazione patologica situata in corrispondenza della neoformazione. La paziente è stata sottoposta a spleno-pancreasectomia corpo-coda. L’esame istologico ha dimostrato un nf-PNET di grado intermedio (G2) stenosante il vena lienale e stenosante il dotto di Wirsung, con pancreatite perilesionale. L’immunoistochimica ha mostrato un immunofenotipo positivo per CAM5.2, sinaptofisina (> 95%) e cromogranina (60%), con espressione di somatostatina intratumorale negativa. CONCLUSIONE: Sebbene raramente un nf-PNETS può essere la causa di grave pancreatite acuta non biliare da compressione del sistema duttale pancreatico. Nei casi in cui la PET / CT68Ga non può essere eseguita, la scintigrafia total body con Octreoscan® rimane il metodo più utilizzato per la diagnosi dei PNET e l’identificazione delle eventuali lesioni extra-pancreatiche. La cromogranina e la sinaptofisina sono confermate come marcatori specifici del differenziamento neuroendocrino.BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) are uncommon, representing <5% of all pancreatic neoplasms, divided into functioning PNETs with secreted hormone cause of specific symptoms, and non-functioning PNETs (nf- PNETs) characterized by delayed diagnosis with metastases and clinical manifestations of compressive effects. Surgical approach is recommended for functioning and nf-PNETs >2 cm in diameter. CASE REPORT: A 76-year-old woman was admitted to the UOC-University-Surgery Hospital "A. Fiorini" in Terracina for nausea and pain in the upper abdominal quadrants with dorso-lumbar irradiation, arising after the evening meal. After the haematochemistry tests and the instrumental investigations, the diagnosis of acute, severe halitiasic pancreatitis was made. Conventional US, CCT, CE-MRI and EUS showed a 2.8cm diameter lesion in the head-body junction of the pancreas. FNA-cytological examination did not found the presence of atypical pancreatic cells. Total-body scintigraphy with Octreoscan® documented a pathological hypercaptation area located in correspondence with the neoformation. The patient underwent a body-tail spleno-pancreatectomy. The histological examination showed an intermediate grade (G2) nf-PNET infiltrating the lienal vein and stenosing the Wirsung duct, with perilesional pancreatitis. Immunohistochemistry showed CAM 5.2, Synaptophysin (>95%) and Chromogranin (60%) positive immunophenotype, with negative intratumoral Somatostatin expression. CONCLUSION: Although rarely, nf-PNETS may be the cause of severe non-biliary acute pancreatitis from pancreatic ductal system compression. In cases where PET/CT68Ga cannot be performed, total-body scintigraphy with Octreoscan® remains the most widely used method for the diagnosis of PNETs and the identification of extra-pancreatic lesions. Chromogranin and Synaptophysin are confirmed as specific markers of neuroendocrine differentiation. KEY WORDS: Acute pancreatitis, Chromogranin, Pancreatic neuroendocrine tumor, Synaptophysin, Somatostatin

Role of p38 MAPK and RNA-dependent protein kinase (PKR) in hepatitis C virus core-dependent nuclear delocalization of cyclin B1.

Some hepatitis C virus (HCV) proteins, including core protein, deregulate the cell cycle of infected cells, thereby playing an important role in the viral pathogenesis of HCC. Thus far, there are only few studies that have deeply investigated in depth the effects of the HCV core protein expression on the progression through the G1/S and G2/M phases of the cell cycle. To shed light on the molecular mechanisms by which the HCV core protein modulates cell proliferation, we have examined its effects on cell cycle in hepatocarcinoma cells. We show here that HCV core protein perturbs progression through both the G1/S and the G2/M phases, by modulating the expression and the activity of several cell cycle regulatory proteins. In particular, our data provided evidence that core-dependent deregulation of the G1/S phase and its related cyclin-CDK complexes depends upon the ERK1/2 pathway. On the other hand, the viral protein also increases the activity of the cyclin B1-CDK1 complex via the p38 MAPK and JNK pathways. Moreover, we show that HCV core protein promotes nuclear import of cyclin B1, which is affected by the inhibition of both the p38 and the RNA-dependent protein kinase (PKR) activities. The important role of p38 MAPK in regulating G2/M phase transition has been previously documented. It is becoming clear that PKR has an important role in regulating both the G1/S and the G2/M phase, in which it induces M phase arrest. Based on our model, we now show, for the first time, that HCV core expression leads to deregulation of the mitotic checkpoint via a p38/PKR-dependent pathway

Hypothalamo-pituitary axis and puberty

Puberty is a complex process that culminates in the acquisition of psychophysical maturity and reproductive capacity. This elaborate and fascinating process marks the end of childhood. Behind it lies a complex, genetically mediated neuroendocrine mechanism through which the gonads are activated thanks to the fine balance between central inhibitory and stimulating neuromodulators and hormones with both central and peripheral action. The onset of puberty involves the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, supported by the initial “kiss” between kisspeptin and the hypothalamic neurons that secrete GnRH (the GnRH “pulse generator”). This pulsatile production of GnRH is followed by a rise in LH and, consequently, in gonadal steroids. The onset of puberty varies naturally between individuals, and especially between males and females, in the latter of whom it is typically earlier. However, pathological variations, namely precocious and delayed puberty, are also possible. This article reviews the scientific literature on the physiological mechanisms of puberty and the main pathophysiological aspects of its onset

Adverse pathophysiological influence of early testosterone therapy on the testes of boys with higher grade sex chromosome aneuploidies (HGAs): a retrospective, cross-sectional study

Purpose: Higher grade aneuploidies (HGAs) of the male sex chromosomes are a rare genetic group of pathologies caused by nondisjunction meiotic events. The aim of this study was to evaluate the impact of early androgenic therapy on the testicular secretory hormone profile, and the pathophysiological implications. Patients and methods: In this cross-sectional study, 18 HGA subjects aged 6–8 years were recruited. They were divided into two groups, based on whether or not they had previously undergone testosterone therapy (group 1: 11 untreated subjects; group 2: 7 treated subjects). Serum FSH, LH, testosterone (T), inhibin B (INHB) and anti-Müllerian hormone (AMH) were determined, and auxological parameters were assessed. Five group 1 patients and four group 2 patients were treated with hCG (human chorionic gonadotropin) for inguinal cryptorchidism; their hormone profile and auxological parameters were assessed both pre- and post-hCG treatment. Results: Group 1 subjects showed significantly higher testicular volume and higher levels of AMH and INHB (p < 0.0001). Subjects who had undergone hCG therapy showed a significantly higher testicular volume, penis length (respectively, p = 0.008 and p = 0.0005 for group 1 and p = 0.04 and p = 0.001 for group 2) and T (p = 0.005 for group 1 and p = 0.004 for group 2). Conclusions: HGA patients undergoing early testosterone therapy show an earlier and persistent suppression of testicular secretory function. At this age, the testes are still responsive to stimulation with hCG. The selection of patients to be treated must be accompanied by a thorough clinical and hormonal evaluation

A study of the prevalence and genotypes of Giardia duodenalis infecting kennelled dogs

Giardia duodenalis is a protozoan parasite of animals that is zoonotic. Given the capacity of this organism to spread via the faecal–oral route, animals held in overcrowded and unhygienic conditions are at high risk of infection. Faecal samples from dogs in three kennels in Rome were examined by microscopy and PCR for G. duodenalis, and the prevalence data generated were correlated with variables such as kennel identity, age of dog, length of time the dog had been kennelled and clinical signs. The overall prevalence of the parasite in the faecal samples was 20.5% and was higher in samples from the largest kennel, which had the greatest turnover of dogs, and in faecal samples from younger animals. Giardia cysts were found more frequently in diarrhoeic animals but were also found in dogs with no clinical signs. Although the finding that the majority of isolates were dog-specific rather than zoonotic genotypes suggests that the zoonotic risk from this pathogen is less than previously thought, the higher prevalence of infection in younger dogs may pose a specific public health issue as such animals are more frequently re-homed with families. 2008 Elsevier Ltd. All rights reserved

Investigation of a VLSI neural network chip as part of a secondary vertex trigger

Abstract An analog VLSI neural network chip (ETANN) has been trained to detect secondary vertices in simulated data for a fixed target heavy flavour production experiment. The detector response and associative memory track finding were modelled by a simulation, but the vertex detection was performed in hardware by the neural network chip and requires only a few microseconds per event. The chip correctly tags 30% of the heavy flavour events while rejecting 99% of the background, and is thus well adapted for secondary vertex triggering applications. A general purpose VME module for interfacing the ETANN to experiments, equipped with ADC/DAC circuits and a 68070 CPU, is also presented

Seasonally Forced SIR Systems Applied to Respiratory Infectious Diseases, Bifurcations, and Chaos

We investigate models to describe respiratory diseases with fast mutating virus pathogens such that after some years the aquired resistance is lost and hosts can be infected with new variants of the pathogen. Such models were initially suggested for respiartory diseases like influenza, showing complex dynamics in reasonable parameter regions when comparing to historic empirical influenza like illness data, e.g., from Ille de France. The seasonal forcing typical for respiratory diseases gives rise to the different rich dynamical scenarios with even small parameter changes. Especially the seasonality of the infection leads for small values already to period doubling bifurcations into chaos, besides additional coexisting attractors. Such models could in the future also play a role in understanding the presently experienced COVID-19 pandemic, under emerging new variants and with only limited vaccine efficacies against newly upcoming variants. From first period doubling bifurcations, we can eventually infer at which close by parameter regions complex dynamics including deterministic chaos can arise.Marie Skłodowska-Curie grant agreement No. 79249

PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile

Purpose: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases. Methods: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples. Results: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number. Conclusions: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer