Enhancing quality of life in head and neck cancer patients: a comparative analysis of 3D exoscope-assisted surgery vs. traditional approaches.

Introduction: The increasing population of survivors of head and neck carcinomas is becoming more conspicuous. Consequently, the pivotal role of quality of life, particularly elucidated through the assessment of dysphagia and dysphonia, is progressively influencing the decision-making process. The current study aims to assess whether VITOM 3D could offer a comparable post-treatment quality of life to traditional approaches for patients with laryngeal cancer and oro-hypopharyngeal cancer. Methods: A case series of laryngeal cancer and oro-hypopharyngeal cancer patients treated either with an exoscopic-assisted surgical setup and with conventional treatments (transoral microsurgery and radio-chemotherapy) at the Otolaryngology Unit of IRCCS San Martino Hospital, Genoa, is presented. The post-treatment quality of life of the two cohorts were compared through the administration of the University of Washington Quality of Life Questionnaire, Voiceik Handicap Index-10, M.D. Anderson Dysphagia Inventory were administrated to both cohorts of patients. Results: In the laryngeal cancer group, a total of 79 patients were included. Of these, 50.1% underwent transoral exoscope-assisted surgery, while 49.9% underwent primary transoral microscopic-assisted surgical approach. No significant differences were observed in terms of the University of Washington Quality of Life Questionnaire and Voice Handicap Index-10 between the two subgroups. Conversely, in the oro-hypopharyngeal cancer group, 43 patients were included. Of these, 37.2% underwent primary transoral exoscope-assisted surgery, while 62.8% received (chemo)radiotherapy. No notable differences were reported in terms of the University of Washington Quality of Life Questionnaire and M.D. Anderson Dysphagia Inventory between the transoral exoscope-assisted surgery and (chemo)radiotherapy subgroups. Conclusions: Assessments of quality of life, conducted through the University of Washington Quality of Life Questionnaire questionnaire, dysphonia evaluations using the Voice Handicap Index-10, and dysphagia assessments employing the M.D. Anderson Dysphagia Inventory questionnaire, demonstrate analogous outcomes between conventional treatment modalities and transoral interventions utilizing the 3D exoscope.

Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication.

OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. CONCLUSION: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3230-3237, 2024.

Exploring the landscape of AI-assisted decision-making in head and neck cancer treatment: a comparative analysis of NCCN guidelines and ChatGPT responses.

PURPOSE: Recent breakthroughs in natural language processing and machine learning, exemplified by ChatGPT, have spurred a paradigm shift in healthcare. Released by OpenAI in November 2022, ChatGPT rapidly gained global attention. Trained on massive text datasets, this large language model holds immense potential to revolutionize healthcare. However, existing literature often overlooks the need for rigorous validation and real-world applicability. METHODS: This head-to-head comparative study assesses ChatGPT's capabilities in providing therapeutic recommendations for head and neck cancers. Simulating every NCCN Guidelines scenarios. ChatGPT is queried on primary treatments, adjuvant treatment, and follow-up, with responses compared to the NCCN Guidelines. Performance metrics, including sensitivity, specificity, and F1 score, are employed for assessment. RESULTS: The study includes 68 hypothetical cases and 204 clinical scenarios. ChatGPT exhibits promising capabilities in addressing NCCN-related queries, achieving high sensitivity and overall accuracy across primary treatment, adjuvant treatment, and follow-up. The study's metrics showcase robustness in providing relevant suggestions. However, a few inaccuracies are noted, especially in primary treatment scenarios. CONCLUSION: Our study highlights the proficiency of ChatGPT in providing treatment suggestions. The model's alignment with the NCCN Guidelines sets the stage for a nuanced exploration of AI's evolving role in oncological decision support. However, challenges related to the interpretability of AI in clinical decision-making and the importance of clinicians understanding the underlying principles of AI models remain unexplored. As AI continues to advance, collaborative efforts between models and medical experts are deemed essential for unlocking new frontiers in personalized cancer care.

Patterns of radiological response to tebentafusp in patients with metastatic uveal melanoma.

Metastatic uveal melanoma (mUM) is a rare type of melanoma with poor outcomes. The first systemic treatment to significantly prolong overall survival (OS) in patients with mUM was tebentafusp, a bispecific protein that can redirect T-cells to gp-100 positive cells. However, the objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) may underestimate the clinical impact of tebentafusp. As metabolic response assessed by PET Response Criteria in Solid Tumors (PERCIST) has been reported to better correlate with clinical outcome, we here compared the patterns of radiological and morphological responses in HLA-A*02:01-positive patients with mUM treated with tebentafusp. In the 19 enrolled patients, RECIST showed an overall response rate (ORR) of 10%, median progression-free survival of 2.8 months (95% CI 2.5-8.4), and median OS (mOS) of 18.8 months. In 10 patients, where both RECIST and PERCIST evaluation was available, the ORR was 10% for both; however, the PFS was longer for PERCIST compared to RECIST, 3.1 and 2.4 months, respectively. A poor agreement between the criteria was observed at all assessments (Cohen's kappa ≤0), yet they differed significantly only at the first on-treatment imaging ( P  = 0.037). Elevated baseline LDH and age were associated with an increased risk for RECIST progression, while lymphocyte decrease after the first infusions correlated to reduced risk of RECIST progression. Detectable ctDNA at baseline did not correlate with progression. Early response to tebentafusp may be incompletely captured by conventional imaging, leading to a need to consider both tumor morphology and metabolism.

Functional outcomes of soft palate reconstruction after oncologic surgery: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to analyze functional outcomes of soft palate reconstruction after oncologic surgery. METHODS: This study was conducted in conformity with the PRISMA statement. A single arm meta-analysis was performed for feeding tube dependence (FTD) (primary outcome), velopharyngeal insufficiency (VPI) and hypernasality (HN) (secondary outcomes) incidences. RESULTS: A total of 510 patients (males: 77.75%, n = 353/454) with a median age of 58 years (n = 480/510; 95% CI 57.0-61.0) who underwent soft palate surgical resection with primary reconstruction were included. Overall, the cumulative FTD rate was 1.55% (n = 28/510; 95% CI 0.24-3.96%), the VPI rate was 22.18% (n = 119/379; 95% CI 12.99-33.02%), and the HN rate was 33.01% (n = 88/234; 95% CI 19.03-46.61%). CONCLUSIONS: Soft palate reconstruction results in a low incidence of FTD, and most patients resume a full oral diet. Both obturators, primary closure, local and free flaps seem good reconstructive options. Nevertheless, more specific postoperative functional deficiencies like VPI and HN owns higher incidences, potentially affecting the quality of the swallowing and speaking function and the patient's quality of life.

The Prognostic Value of a Single, Randomly Timed Circulating Tumor DNA Measurement in Patients with Metastatic Melanoma.

Melanoma currently lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Circulating tumor DNA (ctDNA), originating from tumor cells and detectable in plasma, has emerged as a possible biomarker in patients with metastatic melanoma. In this retrospective, single-center study, we collected 129 plasma samples from 79 patients with stage IIIB-IV melanoma as determined by the American Joint Committee on Cancer (AJCC, 8th edition). For the determination of ctDNA levels, we used eight different assays of droplet digital polymerase chain reaction (ddPCR) to detect the most common hotspot mutations in the BRAF and NRAS genes. The aim of the study was to investigate the association of the detectability of ctDNA at a non-prespecified time point in a patient's treatment with tumor progression, and to correlate ctDNA with commonly used biomarkers (protein S100, LDH, and CRP). Patients with detectable ctDNA progressed more frequently in PET-CT within 12 months than those without detectable ctDNA. Detectability of ctDNA was associated with shorter OS in univariate and multivariate analyses. ctDNA was detectable in a statistically significantly larger proportion of patients with distant metastases (79%) than in patients with no distant metastases or only intracranial metastases (32%). Elevated protein S100 and CRP correlated better with detectable ctDNA than LDH. This study supports the potential of ctDNA as a prognostic biomarker in patients with metastatic melanoma. However, additional prospective longitudinal studies with quantitative assessments of ctDNA are necessary to investigate the limitations and strengths of ctDNA as a biomarker.

A Comparative Study of Real-Time RT-PCR-Based SARS-CoV-2 Detection Methods and Its Application to Human-Derived and Surface Swabbed Material.

Real-time RT-PCR remains a gold standard in the detection of various viral diseases. In the coronavirus 2019 pandemic, multiple RT-PCR-based tests were developed to screen for viral infection. As an emergency response to increasing testing demand, we established a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR diagnostics platform for which we compared different commercial and in-house RT-PCR protocols. Four commercial, one customized, and one in-house RT-PCR protocols were evaluated with 92 SARS-CoV-2-positive and 92 SARS-CoV-2-negative samples. Furthermore, economical and practical characteristics of these protocols were compared. In addition, a highly sensitive digital droplet PCR (ddPCR) method was developed, and application of RT-PCR and ddPCR methods on SARS-CoV-2 environmental samples was examined. Very low limits of detection (1 or 2 viral copies/µL), high sensitivities (93.6% to 97.8%), and high specificities (98.7% to 100%) for the tested RT-PCR protocols were found. Furthermore, the feasibility of downscaling two of the commercial protocols, which could optimize testing capacity, was demonstrated. Tested commercial and customized RT-PCR detection kits show very good and comparable sensitivity and specificity, and the kits could be further optimized for use on SARS-CoV-2 viral samples derived from human and surface swabbed samples.

Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations.

Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancer needs to be analyzed in further studies.

Breast implant-associated anaplastic large cell lymphoma: A rare case report of lymphoma in the form of a pericapsular solid formation.

Breast cancer is the most frequently diagnosed cancer in women in the western world and a major cause of premature death. Consequently, breast implants are widely used for breast reconstruction. Despite this, the prevalence of implant complications is low. Given widespread use of breast implants, there is an increased awareness of the risk for developing a breast implant associated- anaplastic large cell Lymphoma (BI-ALCL) although rare. Clinical presentation is variable and may include a palpable mass in the breast or axilla, generalized breast pain, or breast firmness. The estimated incidence of BI-ALCL is <3 per 1 million person years, approximately 0.1-0.3 per 100 000 women with prostheses per year. Since the publication by Keech and Creech in 1997, which reported the first case of BI-ALCL, an increasing number of BI-ALCL have appeared, in patients with both aesthetic and reconstructive indications. In this paper, we describe a patient who was diagnosed with invasive BIA-ALCL seventeen years after placement of silicone breast implants and was treated with only surgery.

Trastuzumab-related cardiotoxicity in patients with nonlimiting cardiac comorbidity.

BACKGROUND: Significant and symptomatic cardiac comorbidity is a contraindication to adjuvant trastuzumab in breast cancer patients. However, some patients with asymptomatic, nonlimiting cardiac comorbidity and normal baseline left ventricular ejection fraction (LVEF) receive adjuvant trastuzumab in the clinical practice. We sought to describe the tolerability of trastuzumab in these patients. PATIENTS AND METHODS: Retrospective analysis of patients with baseline asymptomatic, nonlimiting cardiac comorbidity receiving adjuvant trastuzumab at six Institutions between July 2007 and January 2016. RESULTS: Thirty-seven patients with HER2-positive, surgery treated breast cancer at high risk of relapse were studied. Median age was 64 years (range 36-82), median baseline LVEF 61% (range 50%-85%). Thirteen patients (35%) received trastuzumab with adjuvant anthracycline and taxane-based regimens, 19 (51%) with taxane-based, three (8%) with off-label vinorelbine and two (5%) with off-label endocrine therapy. Most frequent cardiac comorbidities were ischemic heart disease (35%), valvular disease (30%), atrial fibrillation (19%), and conduction disorders (14%). Nine patients (24.3%) experienced a cardiac event: congestive heart failure (one patient, 3%), asymptomatic LVEF reduction (six patients, 16%), and rhythm disturbances (two patients, 5%). Trastuzumab had to be discontinued either permanently (five patients, 14%) or temporarily (two patients, 5%). At the time of last follow-up visit, all patients showed LVEF within normal limits, except one who had experienced a symptomatic cardiac event (LVEF value at last follow-up 46%). CONCLUSIONS: Caution is needed in patients with significant ongoing cardiovascular risk factors, but when adjuvant trastuzumab is deemed beneficial on breast cancer outcomes, nonlimiting cardiac comorbidity should not preclude treatment.

The science behind autologous fat grafting.

INTRODUCTION: Adipose grafting has undergone significant changes over time. Many different techniques have been followed by trying to improve the quality of the lipoaspirate and the survival of the fat graft after implantation. MATERIAL AND METHODS: The purpose of this review is to analyse the historical evolution of the surgical harvesting and implant technique, describing the changes that have brought significant improvements, revolutionizing the aesthetic and functional results obtainable. RESULTS: A standard fat grafting technique is commonly performed in three stages: harvesting of adipose tissue from a suitable donor site; processing of the lipoaspirate to eliminate cellular debris, acellular oil and excess of infiltrated solution, reinjection of the purified adipose tissue. The most widely used surgical technique was described by Coleman. He modified and corrected the methods and results of his predecessors and proposed an atraumatic protocol for the treatment of adipose tissue.He reported that the key to successful fat grafting lies in the technique. In addition, he noticed that adipose tissue was not only a good filler, but improved the quality of the skin. In fact, fat grafts demonstrated to have not only dermal filler properties but also regenerative potential owing to the presence of stem cells in fat tissue. CONCLUSION: Adipose tissue, actually, is the closest to the ideal filler because it is readily available; easily obtainable, with low donor-site morbidity; repeatable; inexpensive; versatile; and biocompatible. There is an abundance of literature supporting the efficacy of fat grafting in both aesthetic and reconstructive cases. Recent studies have shown the utility of adipose-derived stem cells in the improvement of wound healing, describing their ability to regenerate soft tissues and their remodelling capacity provided by their unique cytokine and growth factor profiles.Despite ongoing concerns about survival and longevity of fat grafts after implantation and unpredictability of long-term outcome, fat has been successfully used as a filler in many differ clinic situation.

A journey through liposuction and liposculture: Review.

INTRODUCTION: Nowadays, liposuction is the most frequently performed aesthetic surgery procedure in Western Countries. This technique has had rapid development since the 1970s, when it was experimented for the first time by A. and G. Fischer. It is currently widely used in clinical practice for many different situations in aesthetic, reconstructive and functional fields. MATERIALS AND METHODS: This review aims to describe the historical evolution of liposuction by analyzing the transformation of the method in function of the introduction of innovative ideas or instruments. We have also focused on reporting the major clinical applications of this surgical technique, applicable to almost the entire body surface. We finally analyzed the complications, both major and minor, associated with this surgical technique. RESULTS: Liposuction is mainly used to correct deep and superficial fat accumulations and remodel the body contour. It has become an essential complementary technique to enhance the aesthetic result of many other aesthetic procedures such as reduction mammoplasty, abdominoplasty, brachioplasty, thigh lift and post bariatric body contouring. However, it can be largely used for the treatment of innumerable pathologies in reconstructive surgery such as lipomas, lipedema, lipodystrophies, pneudogynecomastia and gynecomastia, macromastia e gigantomastia, lymphedema and many others. The complication rate is very low, especially when compared with conventional excisional surgery and the major, complications are generally associated with improper performance of the technique and poor patient management before and after surgery. CONCLUSION: Liposuction is a safe, simple and effective method of body contouring. It has enormous potential for its application in ablative and reconstructive surgery, far from the most common aesthetic processes with a very low complication rate.

Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.

It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants. The resulting reduction of BET protein levels sensitized cancer cells to BET inhibitors. Conversely, prostate cancer-specific SPOP mutations resulted in impaired degradation of BETs, promoting their resistance to pharmacologic inhibition. These results uncover an oncogenomics paradox, whereby mutations mapping to the same domain evoke opposing drug susceptibilities. Specifically, we provide a molecular rationale for the use of BET inhibitors to treat patients with endometrial but not prostate cancer who harbor SPOP mutations.

Tracking the origin of simultaneous endometrial and ovarian cancer by next-generation sequencing - a case report.

BACKGROUND: Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. CASE PRESENTATION: In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary. The patient developed a metachronous lung metastasis of an endometrioid adenocarcinoma four years after hyster- and adnexectomy, vaginal brachytherapy and treatment with the synthetic steroid tibolone. Removal of the metastasis and megestrol treatment for seven years led to a complete remission. A total of 409 genes from the Ampliseq Comprehensive Cancer Panel (Ion Torrent, Thermo Fisher) were analysed by next generation sequencing and mutations in 10 genes, including ARID1A, CTNNB1, PIK3CA and PTEN were identified and confirmed by Sanger sequencing. Primary endometrial as well as ovarian cancer showed an identical mutational profile, suggesting the presence of an ovarian metastasis of the endometrial cancer, rather than a simultaneous endometrial and ovarian cancer. The metachronous lung metastasis showed a different mutational profile compared to the primary cancer. Immunohistochemical staining of the corresponding proteins suggested that the tumour development was driven by alterations in the protein function rather than by changes of the protein abundance in the cell. CONCLUSIONS: Our results have demonstrated next generation sequencing as a valuable tool in the differentiation of synchronous primary tumours and metastases, which has an important impact on the clinical decision making process. Similar to breast cancer, targeted therapies based on mutational tumour profiling will become increasingly important in endometrial and ovarian cancer. In summary, our results support the usage of next generation sequencing as a supplementary diagnostic tool, assisting in personalized precision medicine.

Cisplatin+Vinorelbine Treatment of Recurrent or Metastatic Salivary Gland Malignancies (RMSGM): A Final Report on 60 Cases.

OBJECTIVES: Recurrent or metastatic salivary gland malignancies (RMSGM) are not suitable for conventional treatment. We report the clinical outcomes of 60 patients affected by RMSGM who were treated with DDP+VNB as a first-line or second-line scheme. MATERIALS AND METHODS: Sixty patients between 2001 and 2008, affected by RMSGM were enrolled in this cohort prospective study; they received the following first-line or second-line chemotherapy (CT), for a maximum of 6 cycles: DDP at 80 mg/m on day 1+VNB at 25 mg/m on day 1 and 8, at 3-week intervals. RESULTS: Seventy percent of the patients received DDP+VNB as the first-line CT and 30% of them received it as the second-line CT. After 5 cycles (median) of first-line DDP+VNB, 7% of the patients achieved a complete response, 24% achieved a partial response, 33% achieved an no change, and 36% achieved a PD. After 4 cycles (median) of second-line CT, 0 patients achieved a CR, 5% achieved a PR, 33% achieved an NC, and 62% achieved a PD. The median overall survival period was 10 months for those who received the first-line CT and 4 months for those who received the second-line CT. The best ORR (54%) and median survival were observed, during first-line treatment, in adenocarcinomas, whereas undifferentiated tumours were unresponsive with a poor median survival (4.6 mo). CONCLUSIONS: Adenocarcinomas show the best response and prognosis with DDP+VNB scheme that seems to be an effective and well-tolerated first-line CT for RMSGM, whereas it has only low palliative activity as a second-line CT.

Two-Stage Tissue-Expander Breast Reconstruction: A Focus on the Surgical Technique.

OBJECTIVE: Breast cancer, the most common malignancy in women, comprises 18% of all female cancers. Mastectomy is an essential intervention to save lives, but it can destroy one's body image, causing both physical and psychological trauma. Reconstruction is an important step in restoring patient quality of life after the mutilating treatment. MATERIAL AND METHODS: Tissue expanders and implants are now commonly used in breast reconstruction. Autologous reconstruction allows a better aesthetic result; however, many patients prefer implant reconstruction due to the shorter operation time and lack of donor site morbidity. Moreover, this reconstruction strategy is safe and can be performed in patients with multiple health problems. Tissue-expander reconstruction is conventionally performed as a two-stage procedure starting immediately after mammary gland removal. RESULTS: Mastectomy is a destructive but essential intervention for women with breast cancer. Tissue expansion breast reconstruction is a safe, reliable, and efficacious procedure with considerable psychological benefits since it provides a healthy body image. CONCLUSION: This article focuses on this surgical technique and how to achieve the best reconstruction possible.

Detection of CCNE1/URI (19q12) amplification by in situ hybridisation is common in high grade and type II endometrial cancer.

One TCGA subgroup of endometrial cancer (EC) is characterised by extensive genomic DNA copy number alterations. CCNE1 located at 19q12 is frequently amplified in EC and a target for anti-cancer therapy. The relevance of URI, also located at 19q12, is unknown. To evaluate the prevalence of 19q12 (CCNE1/URI) in EC, we investigated different histologic types by in situ hybridisation (ISH) and copy number assay. We applied a previously established 19q12 ISH for the detection of CCNE1/URI copy numbers in EC (n = 270) using conventional bright field microscopy. In a subset (n = 21), 19q12 amplification status was validated by OncoScan assay. Manual ISH was controlled by a recently developed computational ISHProfiler algorithm. Associations of 19q12 status with Cyclin E1, URI and p53 expression, and clinico-pathological parameters were tested.Amplification of 19q12 (CCNE1/URI) was found in 10.4% (28/270) and was significantly associated with type II EC (high grade and non-endometrioid; p < 0.0001), advanced FIGO stage (p = 0.001), high Cyclin E1 expression (p = 0.008) and aberrant p53 expression (p = 0.04). 19q12 ISH data were confirmed by OncoScan and computational ISHProfiler techniques. The 19q12 in situ hybridisation is a feasible and robust biomarker assay in molecular pathology. Amplification of CCNE1/URI predominantly occurred in type II endometrial cancer. Prospective clinical trials are warranted to assess the utility of combined 19q12 amplification and Cyclin E1/URI protein expression analysis for the prediction of therapeutic response to chemotherapy and/or cyclin-dependent kinase inhibitors in patients with endometrial cancer.

MeCP2 Related Studies Benefit from the Use of CD1 as Genetic Background.

MECP2 mutations cause a number of neurological disorders of which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through the years; their validity is demonstrated by the presence of a broad spectrum of phenotypes largely mimicking those manifested by RTT patients. These mouse models, between which the C57BL/6 Mecp2tm1.1Bird strain probably represents the most used, enabled to disclose much of the roles of Mecp2. However, small litters with little viability and poor maternal care hamper the maintenance of the colony, thus limiting research on such animals. For this reason, past studies often used Mecp2 mouse models on mixed genetic backgrounds, thus opening questions on whether modifier genes could be responsible for at least part of the described effects. To verify this possibility, and facilitate the maintenance of the Mecp2 colony, we transferred the Mecp2tm1.1Bird allele on the stronger CD1 background. The CD1 strain is easier to maintain and largely recapitulates the phenotypes already described in Mecp2-null mice. We believe that this mouse model will foster the research on RTT.

Delayed Diagnosis of Osteonecrosis of the Jaw (ONJ) Associated with Bevacizumab Therapy in Colorectal Cancer Patients: Report of Two Cases.

Medication-induced Osteonecrosis of the Jaw (MRONJ) has been reported not only after use of antiresorptive agents (bisphosphonates and denosumab), but also in cancer patients receiving antiangiogenic agents, alone or combined with antiresorptive drugs. We report two cases of MRONJ observed in colorectal cancer patients after bevacizumab therapy only. MRONJ was diagnosed, respectively, two and seven months after a tooth extraction; both the patients had received two courses of bevacizumab infusions (for a total of 29 and 10 administrations, respectively). We discuss if tooth extraction during or after antiangiogenic therapy could be a potential trigger of MRONJ, but also if an underlying bone disease not evident before oral surgery might be a possible cause. A careful drug history has to be registered by dental specialists in cancer patients before oral surgery and adequate imaging might be obtained to avoid a delayed diagnosis.