Two-year Opioid Prescription Trends in Local Sanitary Agency Naples 3 South, Campania Region, Italy. Descriptive Analyses and AI-based Translational Perspectives.

Aims: This study delves into the two-year opioid prescription trends in the Local Sanitary Agency Naples 3 South, Campania Region, Italy. The research aims to elucidate prescribing patterns, demographics, and dosage categories within a population representing 1.7% of the national total. Perspectives on artificial intelligence research are discussed. Methods: From the original dataset, spanning from January 2022 to October 2023, we processed multiple variables including demographic data, medications, dosages, drug consumption, and administration routes. The dispensing quantity was calculated as defined daily doses (DDD). Results: The analysis reveals a conservative approach to opioid therapy. In subjects under the age of 20, prescriptions accounted for 2.1% in 2022 and declined to 1.4% in 2023. The drug combination paracetamol/codeine was the most frequently prescribed, followed by tapentadol. Approximately two-thirds of the consumption pertains to oral formulations. Transdermal formulations were 15% (fentanyl 9.8%, buprenorphine 5.1%) in 2022; and 16.6% (fentanyl 10%, buprenorphine 6.6%) in 2023. These data were confirmed by the DDD analysis. The trend analysis demonstrated a significant reduction ( p < 0.001) in the number of prescribed opioids from 2022 to 2023 in adults (40-69 years). The study of rapid-onset opioids (ROOs), drugs specifically used for breakthrough cancer pain, showed higher dosage (>267 mcg) consumption among women, whereas a lower dosage (<133 mcg) was calculated for men. Fentanyl pectin nasal spray accounted for approximately one-fifth of all ROOs. Conclusion: Despite limitations, the study provides valuable insights into prescribing practices involving an important study population. The findings underscore the need for tailored approaches to prescribing practices, recognizing the complexities of pain management in different contexts. This research can contribute to the ongoing discourse on opioid use, advocating for innovative strategies that optimize therapeutic outcomes while mitigating potential risks.

Predictive significance of FGFR4 p.G388R polymorphism in metastatic colorectal cancer patients receiving trifluridine/tipiracil (TAS-102) treatment.

BACKGROUND: TAS-102 (Lonsurf®) is an oral fluoropyrimidine consisting of a combination of trifluridine (a thymidine analog) and tipiracil (a thymidine phosphorylation inhibitor). The drug is effective in metastatic colorectal cancer (mCRC) patients refractory to fluorouracil, irinotecan and oxaliplatin. This study is a real-world analysis, investigating the interplay of genotype/phenotype in relation to TAS-102 sensitivity. METHODS: Forty-seven consecutive mCRC patients were treated with TAS-102 at the National Cancer Institute of Naples from March 2019 to March 2021, at a dosage of 35 mg/m2, twice a day, in cycles of 28 days (from day 1 to 5 and from day 8 to 12). Clinical-pathological parameters were described. Activity was evaluated with RECIST criteria (v1.1) and toxicity with NCI-CTC (v5.0). Survival was depicted through the Kaplan-Meyer curves. Genetic features of patients were evaluated with Next Generation Sequencing (NGS) through the Illumina NovaSeq 6000 platform and TruSigt™Oncology 500 kit. RESULTS: Median age of patients was 65 years (range: 46-77). Forty-one patients had 2 or more metastatic sites and 38 patients underwent to more than 2 previous lines of therapies. ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) was 2 in 19 patients. The median number of TAS-102 cycles was 4 (range: 2-12). The most frequent toxic event was neutropenia (G3/G4 in 16 patients). There were no severe (> 3) non-haematological toxicities or treatment-related deaths. Twenty-six patients experienced progressive disease (PD), 21 stable disease (SD). Three patients with long-lasting disease control (DC: complete, partial responses or stable disease) shared an FGFR4 (p.Gly388Arg) mutation. Patients experiencing DC had more frequently a low tumour growth rate (P = 0.0306) and an FGFR4 p.G388R variant (P < 0.0001). The FGFR4 Arg388 genotype was associated with better survival (median: 6.4 months) compared to the Gly388 genotype (median: 4 months); the HR was 0.25 (95% CI 0.12- 0.51; P = 0.0001 at Log-Rank test). CONCLUSIONS: This phenotype/genotype investigation suggests that the FGFR4 p.G388R variant may serve as a new marker for identifying patients who are responsive to TAS-102. A mechanistic hypothesis is proposed to interpret these findings.

rs822336 binding to C/EBPß and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC.

Efficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs as well as to define the molecular mechanisms underlying the role of the identified SNP candidate. rs822336 efficiently predicted response to anti-PD-1/PD-L1 immunotherapy in advanced non-oncogene addicted NSCLC patients as compared to rs2282055 and rs4143815. rs822336 mapped to the promoter/enhancer region of PD-L1, differentially affecting the induction of PD-L1 expression in human NSCLC cell lines as well as their susceptibility to HLA class I antigen matched PBMCs incubated with anti-PD-1 monoclonal antibody nivolumab. The induction of PD-L1 expression by rs822336 was mediated by a competitive allele-specificity binding of two identified transcription factors: C/EBPß and NFIC. As a result, silencing of C/EBPß and NFIC differentially regulated the induction of PD-L1 expression in human NSCLC cell lines carrying different rs822336 genotypes. Analysis by binding microarray further validated the competitive allele-specificity binding of C/EBPß and NFIC to PD-L1 promoter/enhancer region based on rs822336 genotype in human NSCLC cell lines. These findings have high clinical relevance since identify rs822336 and induction of PD-L1 expression as novel biomarkers for predicting anti-PD-1/PD-L1-based immunotherapy in advanced NSCLC patients.

Translational Insights in the Landscape of Salivary Gland Cancers: Ready for a New Era?

Salivary gland carcinomas (SGCs) are rare neoplasms, representing less than 10% of all head and neck tumors, but they are extremely heterogeneous from the histological point of view, their clinical behavior, and their genetics. The guidelines regarding their treatment include surgery in most cases, which can also play an important role in oligometastatic disease. Where surgery cannot be used, systemic therapy comes into play. Systemic therapy for many years has been represented by polychemotherapy, but recently, with the affirmation of translational research, it can also count on targeted therapy, at least in some subtypes of SGCs. Interestingly, in some SGC histotypes, predominant mutations have been identified, which in some cases behave as "driver mutations", namely mutations capable of governing the carcinogenesis process. Targeting these driver mutations may be an effective therapeutic strategy. Nonetheless, it is not always possible to have drugs suitable for targeting driver mutations-and targeting driver mutations is not always accompanied by a clinical benefit. In this review, we will analyze the main mutations predominant in the various histotypes of SGCs.

MiR-449a antagonizes EMT through IL-6-mediated trans-signaling in laryngeal squamous cancer.

MicroRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and in mechanisms of cancer growth and metastases. In this light, miRNAs could be promising therapeutic targets and biomarkers in clinical practice. Therefore, we investigated if specific miRNAs and their target genes contribute to laryngeal squamous cell carcinoma (LSCC) development. We found a significant decrease of miR-449a in LSCC patients with nodal metastases (63.3%) compared with patients without nodal involvement (44%). The AmpliSeq Transcriptome of HNO-210 miR-449a-transfected cell lines allowed the identification of IL6-R as a potential target. Moreover, the downregulation of IL6-R and the phosphorylation reduction of the downstream signaling effectors, suggested the inhibition of the IL-6 trans-signaling pathway. These biochemical effects were paralleled by a significant inhibition of invasion and migration in vitro and in vivo, supporting an involvement of epithelial-mesenchymal transition. These findings indicate that miR-449a contributes to suppress the metastasization of LSCC by the IL-6 trans-signaling block and affects sensitivity to external stimuli that mimic pro-inflammatory conditions.

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab.

BACKGROUND: Immune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial. METHODS: Clinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and <6 months since the start of immunotherapy, respectively). Pretreatment tumor tissue specimen from immunotherapy-treated R/M HNSCC patients was used for PD-L1 (Tumor Proportion Score; Combined Positive Score (CPS)) and Tumor Mutational Burden (Oncopanel TSO500) evaluation and gene expression profiling; classical biomarkers and immune signatures (retrieved from literature) were challenged in the NIVACTOR dataset. RESULTS: Cluster-6 (Cl6) stratification of NIVACTOR cases in high score (n=16, 20%) and low score (n=64, 80%) demonstrated a statistically significant and clinically meaningful improvement in overall survival in the high-score cases (p=0.00028; HR=4.34, 95% CI 1.84 to 10.22) and discriminative ability reached area under the curve (AUC)=0.785 (95% CI 0.603 to 0.967). The association of high-score Cl6 with better outcome was also confirmed in: (1) NIVACTOR progression-free survival (p=4.93E-05; HR=3.71, 95% CI 1.92 to 7.18) and objective-response-rate (AUC=0.785; 95% CI 0.603 to 0.967); (2) long survivors versus short survivors (p=0.00544). In multivariate Cox regression analysis, Cl6 was independent from Eastern Cooperative Oncology Group performance status, PDL1-CPS, and primary tumor site. CONCLUSIONS: These data highlight the presence of underlying biological differences able to predict survival and response following treatment with immunotherapy in platinum-refractory R/M HNSCC that could have translational implications improving treatment selection. TRIAL REGISTRATION NUMBER: EudraCT Number: 2017-000562-30.

Circulating vitamin D level before initiating chemotherapy impacts on the time-to-outcome in metastatic colorectal cancer patients: systematic review and meta-analysis.

BACKGROUND: Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. METHODS: Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot. RESULTS: Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21-1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13-1.70) for patients with lower VD levels, as indicated by fixed-effects models. CONCLUSIONS: Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.

Emerging treatment approaches for triple-negative breast cancer.

Approximately, 15% of global breast cancer cases are diagnosed as triple-negative breast cancer (TNBC), identified as the most aggressive subtype due to the simultaneous absence of estrogen receptor, progesterone receptor, and HER2. This characteristic renders TNBC highly aggressive and challenging to treat, as it excludes the use of effective drugs such as hormone therapy and anti-HER2 agents. In this review, we explore standard therapies and recent emerging approaches for TNBC, including PARP inhibitors, immune checkpoint inhibitors, PI3K/AKT pathway inhibitors, and cytotoxin-conjugated antibodies. The mechanism of action of these drugs and their utilization in clinical practice is explained in a pragmatic and prospective manner, contextualized within the current landscape of standard therapies for this pathology. These advancements present a promising frontier for tailored interventions with the potential to significantly improve outcomes for TNBC patients. Interestingly, while TNBC poses a complex challenge, it also serves as a paradigm and an opportunity for translational research and innovative therapies in the field of oncology.

Oligo-Metastatic Disease in Oncology: Exploring the Limits and the Potential of Genetic Assessment.

Oligo-metastatic disease (OMD) in the field of oncology denotes a distinct subset of metastatic tumors characterized by less aggressive biological behavior and extended survival times in comparison to their widely metastatic counterparts. While there is a general consensus regarding the existence of OMD, there remains a lack of widely accepted criteria for its a priori identification at the time of presentation. This review delves into the concept of OMD, placing a particular emphasis on the significance of understanding the limitations and potential of genetic assessments. It explores how these aspects are crucial in advancing our comprehension of this phenomenon. In a rapidly advancing era of precision medicine, understanding the intricacies of OMD opens up exciting possibilities for tailored treatment approaches. By elucidating the genetic underpinnings and dynamic nature of this condition, we stand to improve patient outcomes and potentially shift the paradigm of metastatic cancer management.

Evaluating Nutritional Risk Factors for Delirium in Intensive-Care-Unit Patients: Present Insights and Prospects for Future Research.

Malnutrition, hypercatabolism, and metabolic changes are well-established risk factors for delirium in critically ill patients. Although the exact mechanisms are not fully understood, there is mounting evidence suggesting that malnutrition can cause a variety of changes that contribute to delirium, such as electrolyte imbalances, immune dysfunction, and alterations in drug metabolism. Therefore, a comprehensive metabolic and malnutrition assessment, along with appropriate nutritional support, may help to prevent or ameliorate malnutrition, reduce hypercatabolism, and improve overall physiological function, ultimately lowering the risk of delirium. For this aim, bioelectrical impedance analysis can represent a valuable strategy. Further research into the underlying mechanisms and nutritional risk factors for delirium is crucial to developing more effective prevention strategies. Understanding these processes will allow clinicians to personalize treatment plans for individual patients, leading to improved outcomes and quality of life in the intensive-care-unit survivors.

Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) have revolutionized the management of many types of solid tumors, including metastatic renal cell carcinoma (mRCC). Both sequential and combinatorial therapeutic strategies utilizing anti-PD-1 monoclonal antibodies (mAbs) and anti-angiogenic tyrosine kinase inhibitors (TKIs) have demonstrated to improve the survival of patients with mRCC as compared to standard therapies. On the other hand, both ICIs and TKIs are well known to potentially cause thyroid disorder adverse events (TDAEs). However, in the context of sequential therapeutic strategy, it is not clear whether prior anti-angiogenic TKI may increase the risk and/or the severity of ICI-related TDAEs. In this work, by describing and analyzing a case series of mRCC patients treated sequentially with prior TKIs and then with ICIs, we investigated the role of prior anti-angiogenic TKI-based treatment as a potential predisposing factor to anti-PD-1-mediated recurrent TDAEs, as well as its potential impact on the clinical characteristics of nivolumab-mediated recurrent TDAEs. Fifty mRCC patients were included in the analysis. TKI-mediated TDAEs were reported in ten out of fifty patients. TKI-mediated TDAEs were characterized by hypothyroidism in all ten patients. Specifically, 40%, 40% and 20% of patients presented grade 1, 2 and 3 hypothyroidisms, respectively. Following tumor progression and during anti-PD-1 nivolumab treatment, five out of ten patients developed anti-PD-1 nivolumab-mediated recurrent TDAEs. Anti-PD-1 nivolumab-mediated recurrent TDAEs were characterized by an early transient phase of thyrotoxicosis and a late phase of hypothyroidism in all five patients. The TDAEs were grade 1 and 2 in four and one patients, respectively. Prior anti-angiogenic TKI did not modify the clinical characteristics of nivolumab-mediated recurrent TDAEs. However, all five patients required an increased dosage of levothyroxine replacement therapy. In conclusion, our work suggests that prior anti-angiogenic TKI-based treatment significantly increases the risk of ICI-mediated recurrent TDAEs in patients with mRCC without modifying their clinical characteristics. The most relevant effect for these patients is the need to increase the dosage of lifelong levothyroxine replacement therapy.

Clostridioides difficile Infection in the Neurorehabilitation Setting: Importance of a Multidisciplinary Approach and Impact of the Fecal Microbiota Transplantation.

Clostridioides difficile infection (CDI) is considered to be one of the most frequent causes of bacterial infectious diarrhea in nosocomial settings. The prolonged hospitalization in bed-ridden conditions and the frequent administration of antibiotic therapy are usually encountered among the risk factors for CDI. Therefore, it is not surprising that CDI rates among rehabilitation hospitals are higher in neurologic facilities. In the neurorehabilitation setting, CDIs, especially if they present with refractory or recurrent aspects, may interrupt the normal course of rehabilitation, influencing, subsequently, the neurological outcomes. CDI treatment depends on the severity of the disease and includes both conservative and surgical approaches, with the latter reserved for severe complicated CDI. Another emerging, highly effective therapeutic option is represented by fecal microbiota transplantation (FMT), which consists of the transfer of screened healthy donor stool to a recipient's gastrointestinal tract. ​​​In this paper, we report two cases of refractory CDI, affecting patients in the neurorehabilitation pathway; both cases were resolved through FMT. On the one hand, our cases provide more evidence of FMT efficacy in refractory CDIs; on the other hand, they emphasize the need for a multidisciplinary approach to grant the best care to CDI patients.

Beyond Body Size: Adiponectin as a Key Player in Obesity-Driven Cancers.

Obesity, a complex and multifactorial disease influenced by genetic, environmental, and psychological factors, has reached epidemic proportions globally, posing a significant health challenge. In addition to its established association with cardiovascular disease and type II diabetes, obesity has been implicated as a risk factor for various cancers. However, the precise biological mechanisms linking obesity and cancer remain largely understood. Adipose tissue, an active endocrine organ, produces numerous hormones and bioactive molecules known as adipokines, which play a crucial role in metabolism, immune responses, and systemic inflammation. Notably, adiponectin (APN), the principal adipocyte secretory protein, exhibits reduced expression levels in obesity. In this scoping review, we explore and discuss the role of APN in influencing cancer in common malignancies, including lung, breast, colorectal, prostate, gastric, and endometrial cancers. Our review aims to emphasize the critical significance of investigating this field, as it holds great potential for the development of innovative treatment strategies that specifically target obesity-related malignancies. Furthermore, the implementation of more rigorous and comprehensive prevention and treatment policies for obesity is imperative in order to effectively mitigate the risk of associated diseases, such as cancer.

From Chaos to Opportunity: Decoding Cancer Heterogeneity for Enhanced Treatment Strategies.

Cancer manifests as a multifaceted disease, characterized by aberrant cellular proliferation, survival, migration, and invasion. Tumors exhibit variances across diverse dimensions, encompassing genetic, epigenetic, and transcriptional realms. This heterogeneity poses significant challenges in prognosis and treatment, affording tumors advantages through an increased propensity to accumulate mutations linked to immune system evasion and drug resistance. In this review, we offer insights into tumor heterogeneity as a crucial characteristic of cancer, exploring the difficulties associated with measuring and quantifying such heterogeneity from clinical and biological perspectives. By emphasizing the critical nature of understanding tumor heterogeneity, this work contributes to raising awareness about the importance of developing effective cancer therapies that target this distinct and elusive trait of cancer.

Changes in gut microbiota composition after 12 weeks of a home-based lifestyle intervention in breast cancer survivors during the COVID-19 lockdown.

Background: Breast cancer (BC) is the second-leading cause of cancer-related death worldwide. This study aimed to investigate the effects of a 12-week home-based lifestyle intervention (based on nutrition and exercise) on gut microbial composition in twenty BC survivors of the MoviS clinical trial (protocol: NCT04818359). Methods: Gut microbiota analysis through 16S rRNA gene sequencing, anthropometrics, Mediterranean Diet (MD) adherence, and cardiometabolic parameters were evaluated before (Pre) and after (Post) the lifestyle intervention (LI). Results: Beneficial effects of the LI were observed on MD adherence, and cardiometabolic parameters (pre vs post). A robust reduction of Proteobacteria was observed after LI, which is able to reshape the gut microbiota by modulating microorganisms capable of decreasing inflammation and others involved in improving the lipid and glycemic assets of the host. A significant negative correlation between fasting glucose and Clostridia_vadinBB60 (r = -0.62), insulin and homeostatic model assessment (HOMA) index and Butyricicoccus genera (r = -0.72 and -0.66, respectively), and HDL cholesterol and Escherichia/Shigella (r = -0.59) have been reported. Moreover, positive correlations were found between MD adherence and Lachnospiraceae_ND3007 (r = 0.50), Faecalibacterium (r = 0.38) and Butyricimonas (r = 0.39). Conclusion: These data suggest that adopting a healthy lifestyle, may contribute to ameliorate several biological parameters that could be involved in the prevention of cancer relapses through the modulation of gut microbiota.

Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians.

BACKGROUND: The genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. RESULTS: The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 × 10-6), with a P-value close to a threshold that takes into account multiple testing. CONCLUSIONS: Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Pharyngocutaneous Fistula in Salvage Laryngectomy: Use of the Stapler Versus Manual Suturing Technique.

A pharyngocutaneous fistula (PCF) is the most common complication after salvage total laryngectomy (STL) with an incidence ranging from 5 to 73%, causing an increase in morbidity and delaying the patient's recovery. A surgical technique to prevent PCF formation is the use of the stapler to suture the pharyngeal mucosa.  We have reviewed the medical files of 91 patients who had undergone STL, dividing the patients into two groups (manual suture vs. stapler), based on the type of pharyngeal suture performed during the STL. We found 12/49 (24.5%) cases of a PCF in group A (manual) and 5/42 (11.9%) cases of a PCF in group B (stapler). There is a statistically significant difference between the two groups with the patients in group B presenting better results in terms of the reduction of the surgical time, the length of the hospital stay and also in the restarting of oral feeding. The advantages of mechanical suturing with the stapler are reduced surgical times, a lower PCF formation rate, which involves an early removal of the nasogastric tube, and reduced hospitalization times. Further studies with a larger case series will be necessary to confirm the results obtained and to standardize the surgical technique.