Sudden Sensorineural Hearing Loss after Lapaoscopic Sleeve Gastrectomy Under General Anaesthesia: A Case Report

We discuss the presentation of a sudden sensorineural hearing loss (SNHL) occurred as a rare complication after laparoscopic sleeve gastrectomy (LSG). Etiology of this complication is not clear, it seems that diverse and complex pathogenetic mechanism are involved so the prevention and treatment seems to be difficult

Hypertension, type 2 diabetes, obesity, and p53 mutations negatively correlate with metastatic colorectal cancer patients’ survival

IntroductionWe studied the predictive and prognostic influences of hypertension (HT), type 2 diabetes (T2D), weight, and p53 mutations in metastatic colorectal cancer (CRC) patients.Patients and methodsT2D was diagnosed according to the ADA criteria. HT was classified according to the ACC/AHA guidelines. BMI (body-mass index) was calculated and classified according to the WHO criteria. TruSigt™Oncology 500 kit was applied to construct the genomic libraries for Next Generation Sequencing (NGS) analysis. The Illumina NovaSeq 6000 technological platform and the Illumina TruSight Oncology 500 bioinformatics pipeline were applied to analyze results. Overall survival (OS) was calculated through Kaplan-Meier curves. Univariate and multivariate analyses were performed to assess the relationships between clinical and/or molecular covariates. Associations between HT, T2D, BMI, p53, and clinical variables were evaluated by the χ2 test. P < 0.05 were considered statistically significant.ResultsTwo-hundred-forty-four patients were enrolled. One-hundred-twenty (49.2%), 110 (45.1%), and 50 (20.5%) patients were affected by overweight, HT, and T2D, respectively. DC (disease control) was achieved more frequently in patients without T2D (83.1%) compared to the diabetic ones (16.9%) (P = 0.0246). DC, KRAS mutational status, T2D, BMI, and concomitant presence of T2D, BMI, and HT associated with survival (P < 0.05). At multivariate analysis, age (≥65 vs. <65 years), response to first-line chemotherapy (DC vs. no DC), and concomitant presence of T2D, BMI, and HT (HR: 4.56; 95% CI: 2.40–8.67; P = 0.0217) emerged as independent prognostic variables. P53 was mutated in 31/53 analyzed cases (60.4%). The most frequent gene variants were p.Arg175His and p.Cys135Tyr. High BMI (>25 kg/m2) associated with occurrence of p53 mutations (P < 0.0001). P53 mutated patients presented a worse prognosis compared to the wild-type ones (HR: 3.21; 95% CI: 1.43–7.23; P = 0.0047).ConclusionDiabetic, hypertensive and overweight metastatic CRC patients are a negative prognostic subgroup deserving specific therapeutic strategies. P53 mutations associate with prognosis and BMI unrevealing complex and unexplored connections between metabolism and cancer occurrence

Micronutrient Deficiencies in Patients Candidate for Bariatric Surgery: A Prospective, Preoperative Trial of Screening, Diagnosis, and Treatment

Bariatric surgery candidates often show preoperative micronutrient deficiency. Although it is documented that a comprehensive micronutrient assessment should be conducted preoperatively to correct the deficiencies before surgery, no previous studies have been effective in correcting deficiencies in sufficient time prior to surgery. Our aim was to identify micronutrient deficiencies preoperatively and correct them before surgery. 50 patients (18 female, 32 male) scheduled for bariatric surgery were assessed for micronutrient status 20 weeks prior to surgery. Baseline levels of vitamin B12, folic acid, 25-vitamin D, vitamin C, vitamin A, vitamin E, iron, zinc, magnesium, and selenium were measured. Data were compared with accepted clinical cutoff values. Patients found to have one or more micronutrient deficiencies were instructed to take daily micronutrient supplements specially formulated for obese patients and were evaluated every 5 weeks over a 20-week period. Nutrient intake was also evaluated before and after supplementation. Micronutrient deficiencies were observed in 40 patients (80 %, 13 female, 27 male). All 40 patients started prescribed supplementation immediately. 20 patients (10 female, 10 male) completed a follow-up at 20 weeks. Herein we found that 10 weeks of preoperative micronutrient supplementation is capable of effectively treating micronutrient deficiencies in our candidates for bariatric surgery. Considering that: 1) no new medication was allowed during the study; 2) patients already under pharmacological treatment did not change their therapy; 3) no statistically differences in nutrient intake were observed before and after the supplementation, we are confident to attribute the improvements in patients' micronutrient status directly to the supplement

Micronutrient Deficiencies in Patients Candidate for Bariatric Surgery: A Prospective, Preoperative Trial of Screening, Diagnosis, and Treatment

Bariatric surgery candidates often show preoperative micronutrient deficiency. Although it is documented that a comprehensive micronutrient assessment should be conducted preoperatively to correct the deficiencies before surgery, no previous studies have been effective in correcting deficiencies in sufficient time prior to surgery. Our aim was to identify micronutrient deficiencies preoperatively and correct them before surgery. 50 patients (18 female, 32 male) scheduled for bariatric surgery were assessed for micronutrient status 20 weeks prior to surgery. Baseline levels of vitamin B12, folic acid, 25-vitamin D, vitamin C, vitamin A, vitamin E, iron, zinc, magnesium, and selenium were measured. Data were compared with accepted clinical cutoff values. Patients found to have one or more micronutrient deficiencies were instructed to take daily micronutrient supplements specially formulated for obese patients and were evaluated every 5 weeks over a 20-week period. Nutrient intake was also evaluated before and after supplementation. Micronutrient deficiencies were observed in 40 patients (80 %, 13 female, 27 male). All 40 patients started prescribed supplementation immediately. 20 patients (10 female, 10 male) completed a follow-up at 20 weeks. Herein we found that 10 weeks of preoperative micronutrient supplementation is capable of effectively treating micronutrient deficiencies in our candidates for bariatric surgery. Considering that: 1) no new medication was allowed during the study; 2) patients already under pharmacological treatment did not change their therapy; 3) no statistically differences in nutrient intake were observed before and after the supplementation, we are confident to attribute the improvements in patients' micronutrient status directly to the supplement

L’ingegnerizzazione tissutale delle cellule paratiroidee

Background. L’ipoparatiroidismo postchirurgico rappresenta un’evenienza tutt’altro che rara dopo intervento di tiroidectomia totale e/o paratiroidectomia totale. I tentativi di trapiantare tessuto paratiroideo sono iniziati nel 1975 con Wells ed i risultati ancora oggi sono alquanto deludenti. Negli ultimi anni grazie a tecniche di ingegneria tissutale si cerca di costruire paratiroidi artificiali,capaci di secernere paratormone, disponibili per il trapianto in pazienti affetti da ipoparatiroidismo iatrogeno. Pazienti e metodi. I paratireociti sono stati ottenuti da paratiroidi di tre pazienti, uremici cronici in emodialisi, operati per iperparatiroidismo secondario. Le colture cellulari ottenute in RPMI sono state successivamente seminate sugli scaffold di collagene (supporti tridimensionali a lenta biodegradazione). Il collagene rappresenta la componente maggioritaria della matrice extracellulare e quindi costituisce un buon substrato su cui le cellule aderiscono e crescono. I terreni di coltura adeguatamente supplementati contenevano bassa concentrazione di calcio e quindi stimolavano in maniera fisiologica i paratireociti a produrre paratormone in maniera costante. Le colture cellulari sono state osservate in microscopia ottica ed in ESEM e sono state sottoposte al test di vitalità MTT fino alla decima settimana. Inoltre è stata misurata la concentrazione di paratormone nel liquido colturale a varie settimane. Risultati. Dopo 24 ore di coltura in RPMI le cellule estratte dalle paratiroidi umane erano quasi tutte adese e raggruppate in clusters tra di loro, a ricordare l’organizzazione ghiandolare. La popolazione cellulare era costituita prevalentemente da paratireociti (90-95%). Seminate sugli scaffold collagenici, a 10 settimane le cellule mantengono una morfologia epithelial-like, arrivando a colonizzare la superficie dello scaffold, conservano una buona progressione proliferativa, associata alla produzione di paratormone. Conclusioni. La scelta di utilizzare paratireociti di pazienti affetti da iperparatiroidismo secondario ha certamente contribuito ad ottenere questi risultati, che, seppur parziali ed in vitro, vanno sperimentati in vivo su modello animale. Il costrutto bioingegnerizzato in scaffold impiantabile nel sottocutaneo può evitare la temuta dispersione delle cellule paratiroidee impiantate e dunque favore la loro agevole rimozione in caso di complicanze. La nostra ricerca ha avuto come obiettivi innanzitutto la realizzazione di colture cellulari di paratireociti umani e successivamente la ingegnerizzazione in vitro di paratiroidi umane all’interno di scaffold tridimensionali collagenici

Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology

Cholangiocarcinoma (CCA) is a malignant neoplasm arising in the epithelium of the biliary tract. It represents the second most common primary liver cancer in the world, after hepatocellular carcinoma, and it constitutes 10–15% of hepatobiliary neoplasms and 3% of all gastrointestinal tumors. As in other types of cancers, recent studies have revealed genetic alterations underlying the establishment and progression of CCA. The most frequently involved genes are APC, ARID1A, AXIN1, BAP1, EGFR, FGFRs, IDH1/2, RAS, SMAD4, and TP53. Actionable targets include alterations of FGFRs, IDH1/2, BRAF, NTRK, and HER2. “Precision oncology” is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from “old” chemotherapies to “new” target-oriented drugs

Intrahepatic cholangiocarcinoma biomarkers: Towards early detection and personalized pharmacological treatments

Cholangiocarcinoma (CCA) is a rare malignancy originating from the biliary tree and is anatomically categorized as intrahepatic (iCCA), perihilar, and extrahepatic or distal. iCCA, the second most prevalent hepatobiliary cancer following hepatocellular carcinoma (HCC), constitutes 5–20 % of all liver malignancies, with an increasing incidence. The challenging nature of iCCA, combined with nonspecific symptoms, often leads to late diagnoses, resulting in unfavorable outcomes. The advanced phase of this neoplasm is difficult to treat with dismal results. Early diagnosis could significantly reduce mortality attributed to iCCA but remains an elusive goal. The identification of biomarkers specific to iCCA and their translation into clinical practice could facilitate diagnosis, monitor therapy response, and potentially reveal novel interventions and personalized medicine. In this review, we present the current landscape of biomarkers in each of these contexts. In addition to CA19.9, a widely recognized biomarker for iCCA, others such as A1BG, CYFRA 21–1, FAM19A5, MMP-7, RBAK, SSP411, TuM2-PK, WFA, etc., as well as circulating tumor DNA, RNA, cells, and exosomes, are under investigation. Advancing our knowledge and monitoring of biomarkers may enable us to improve diagnosis, prognostication, and apply treatments dynamically and in a more personalized manner

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

Metastatic colorectal cancer and type 2 diabetes: prognostic and genetic interactions

The present study was undertaken to analyze prognostic and genetic interactions between type 2 diabetes and metastatic colorectal cancer. Patients' survival was depicted through the Kaplan-Meier product limit method. Prognostic factors were examined through the Cox proportional-hazards regression model, and associations between diabetes and clinical-pathologic variables were evaluated by the chi(2) test. In total, 203 metastatic colorectal cancer patients were enrolled. Lymph nodes (P = 0.0004) and distant organs (> 2 distant sites, P = 0.0451) were more frequently involved in diabetic patients compared with those without diabetes. Diabetes had an independent statistically significant negative prognostic value for survival. Highly selected patients with cancer and/or diabetes as their only illness(es) were divided into three groups: (a) seven oligo-metastatic patients without diabetes, (b) 10 poly-metastatic patients without diabetes, and (c) 12 poly-metastatic diabetic patients. These groups of patients were genetically characterized through the Illumina NovaSeq 6000 (San Diego, CA, USA) platform and TruSigt (TM) Oncology 500 kit, focusing on genes involved in diabetes and colorectal cancer. Gene variants associated with diabetes and cancer were more frequent in patients in group 3. We found that type 2 diabetes is a negative prognostic factor for survival in colorectal cancer. Diabetes-associated gene variants could concur with malignancy, providing a rational basis for innovative models of tumor progression and therapy