Laparoscopic distal pancreatectomy in Italy: A systematic review and meta-analysis

Background The use of laparoscopic distal pancreatectomy (LDP) increased in the past twenty years but the real diffusion of this technique is still unknown as well as the type of centers (high or low volume) in which this procedure is more frequently performed. Data Source A systematic review was performed to evaluate the frequency of LDP in Italy and to compare indications and results in high volume centers (HVCs) and in low volume centers (LVCs). Results From 95 potentially relevant citations identified, only 5 studies were included. A total of 125 subjects were analyzed, of whom 95 (76.0%) were from HVCs and 30 (24.0%) from LVCs. The mean number of LDPs performed per year was 6.5. The mean number of patients who underwent LDP per year was 8.8 in HVCs and 3.0 in LVCs (P<0.001). The most frequent lesions operated on in HVCs were cystic tumors (62.1%, P<0.001) while, in LVCs, solid neoplasms (76.7%, P<0.001). In HVCs, malignant neoplasms were treated with LDP less frequently than in LVCs (17.9% vs 50.0%, P<0.001). Splenectomy was performed for non-oncologic reason frequenter in HVCs than in LVCs (70.2% vs 25.0%, P=0.004). The length of stay was shorter in HVCs than in LVCs (7.5 vs 11.3, P<0.001). No differences were found regarding age, gender, ductal adenocarcinoma treated, operative time, conversion, morbidity, postoperative pancreatic fistula, reoperation and margin status. Conclusions LDPs were frequently performed in Italy. The "HVC approach" is characterized by a careful selection of patients undergoing LDP. The "LVC approach" is based on the hypothesis that LDPs are equivalent both in short-term and long-term results to laparotomic approach. These data are not conclusive and they point out the need for a national register of laparoscopic pancreatectomy

Pre-emptive Laparoscopic Colostomy Creation in Obstructing Locally Advanced Rectal and Anal Cancer Does Not Delay the Starting of Oncological Treatments

Background: Managing patients with obstructing rectal cancer is challenging due to the risks of gastrointestinal obstruction and perforation. This study evaluates the outcomes of pre-emptive laparoscopic colostomy creation in patients with locally advanced rectal and anal cancer to prevent symptoms and facilitate therapy initiation. Methods: This retrospective cohort study includes patients with locally advanced rectal or anal cancer assessed by our Colorectal Multidisciplinary Team from January 2017 to February 2024. Patients who underwent pre-emptive laparoscopic colostomy were compared to a control group of non-obstructing rectal cancer patients who started direct oncological treatment. The primary endpoint was the time from diagnosis to the initiation of oncological treatments. The secondary endpoints were the rate and timing of subsequent radical resection, surgical morbidity and hospital stay. A Weibull regression was used to evaluate the time differences between the groups. Results: There were 37 patients who received pre-emptive laparoscopic colostomy, compared to 207 control patients. The mean time from diagnosis to the start of neoadjuvant therapy was 38.3 ± 2.3 days. Despite higher rates of malnutrition and more advanced stages in the colostomy group, no significant differences were observed in the time to start therapy (p = 0.083) or time to radical resection (p = 0.187) between the groups. The laparoscopic procedure showed low rates of postoperative complications and acceptable lengths of stay. Discussion and Conclusions: Pre-emptive laparoscopic colostomy is a feasible approach for managing obstructing rectal or anal cancer. Treatment timelines were not extended compared to timelines for non-obstructing cases, despite differences in nutritional status and staging. Further prospective studies with larger cohorts are needed to validate these findings and refine treatment protocols for obstructing gastrointestinal malignancies

Severe impact of Covid-19 pandemic on breast cancer care in Italy: a senonetwork national survey

Italy was the first Western country hit by the Coronavirus disease 2019 (COVID-19) pandemic, with over 246,000 documented cases and more than 35,000 deaths related to the infection as of July 26, 2020. The first documented case in Italy was reported on February 18, 2020, introducing a rapid sequence of events. A few towns near Milan and in Veneto were locked down soon thereafter. Finally, the entire country was locked down on March 9, 2020, with a national quarantine, which has severely limited the movement of the entire population except for documented work and health circumstances. Since then, many hospitals have restrained non-emergency admissions and ambulatory services, particularly for non-oncologic patients. Despite many medical and scientific reports on the current pandemic, little is known on the effect and magnitude of this health emergency on the care of patients with breast cancer

Prediction of functional loss in emergency surgery is possible with a simple frailty screening tool

Background: Senior adults fear postoperative loss of independence the most, and this might represent an additional burden for families and society. The number of geriatric patients admitted to the emergency room requiring an urgent surgical treatment is rising, and the presence of frailty is the main risk factor for postoperative morbidity and functional decline. Frailty assessment in the busy emergency setting is challenging. The aim of this study is to verify the effectiveness of a very simple five-item frailty screening tool, the Flemish version of the Triage Risk Screening Tool (fTRST), in predicting functional loss after emergency surgery among senior adults who were found to be independent before surgery. Methods: All consecutive individuals aged 70 years and older who were independent (activity of daily living (ADL) score ≥5) and were admitted to the emergency surgery unit with an urgent need for abdominal surgery between December 2015 and May 2016 were prospectively included in the study. On admission, individuals were screened using the fTRST and additional metrics such as the age-adjusted Charlson Comorbidity Index (CACI) and the ASA score. Thirty- and 90-day complications and postoperative decline in the ADL score where recorded. Regression analysis was performed to identify preoperative predictors of functional loss. Results: Seventy-eight patients entered the study. Thirty-day mortality rate was 12.8% (10/78), and the 90-day overall mortality was 15.4% (12/78). One in every four patients (17/68) experienced a significant functional loss at 30-day follow-up. At 90-day follow-up, only 3/17 patients recovered, 2 patients died, and 12 remained permanently dependent. On the regression analysis, a statistically significant correlation with functional loss was found for fTRST, CACI, and age≥85 years old both at 30 and 90 days after surgery. fTRST≥2 showed the highest effectiveness in predicting functional loss at 90 days with AUC 72 and OR 6.93 (95% CI 1.71–28.05). The institutionalization rate with the need to discharge patients to a healthcare facility was 7.6% (5/66); all of them had a fTRST≥2. Conclusion: fTRST is an easy and effective tool to predict the risk of a postoperative functional decline and nursing home admission in the emergency setting

Gene expression profile of human colon cancer cells treated with cross-reacting material 197, a diphtheria toxin non-toxic mutant

Cross-Reacting Material 197 (CRM197) is a diphtheria toxin non-toxic mutant that has shown anti-tumor activity in mice and humans. It is still unclear whether this anti-tumorigenic effect depends on its strong inflammatory- immunological property, its ability to inhibit heparin-binding epidermal growth factor (HB-EGF), or even its possible weak toxicity. CRM197 is utilized as a specific inhibitor of HB-EGF that competes for the epidermal growth factor receptor (EGFR), overexpressed in colorectal cancer and implicated in its progression. In this study we evaluate the effects of CRM197 on HT-29 human colon cancer cell line behaviour and, for CRM197 recognized ability to inhibit HB-EGF, its possible influence on EGFR activation. In particular, while HT-29 does not show any reduction of viability after CRM197 treatment (MTT modified assay), or changes in cell cycle distribution (flow cytometry), in EGFR localization, phospho-EGFR detected signals (immunohistochemistry) or in morphology (scanning electron microscopy, SEM) they show a change in the gene expression profile by microarray analysis (cDNA microarray SS-H19k8). The overexpression of genes like protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA), guanine nucleotide-binding protein G subunit alpha-1(GNAI1) and butyrophilin, subfamily 2, member A1 (BTN2A1) has been confirmed with real-time-qPCR. This is the first study where the CRM197 treatment on HT-29 shows a possible scarce implication of endogenous HB-EGF on EGFR expression and cancer cell development. At the same time, our results show the alteration of a specific and selected number of genes.Fil: Rivetti, S.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Lauriola, M.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Voltattorni, M.. Universidad de Bologna; ItaliaFil: Bianchini, Michele. Fundación para la Investigación, Docencia y Prevención del Cáncer; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martini, D.. Universidad de Bologna; ItaliaFil: Ceccarelli, C.. Universidad de Bologna; ItaliaFil: Palmieri, A.. Università di Ferrara; ItaliaFil: Mattei, G.. Universidad de Bologna; Italia. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; ItaliaFil: Franchi, M.. Universidad de Bologna; ItaliaFil: Ugolini, G.. Universidad de Bologna; ItaliaFil: Rosati, G.. Universidad de Bologna; ItaliaFil: Montroni, I.. Universidad de Bologna; ItaliaFil: Taffurelli, M.. Universidad de Bologna; ItaliaFil: Solmi, Rosella. Centro Di Ricerca In Genetica Molecolare Fondazione Carisbo; Italia. Universidad de Bologna; Itali

Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence

Background Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells. Results We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3 ' snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs' guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation. Conclusions Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions

Beta-Catenin/HuR Post-Transcriptional Machinery Governs Cancer Stem Cell Features in Response to Hypoxia

Hypoxia has been long-time acknowledged as major cancer-promoting microenvironment. In such an energy-restrictive condition, post-transcriptional mechanisms gain importance over the energy-expensive gene transcription machinery. Here we show that the onset of hypoxia-induced cancer stem cell features requires the beta-catenin-dependent post-transcriptional up-regulation of CA9 and SNAI2 gene expression. In response to hypoxia, beta-catenin moves from the plasma membrane to the cytoplasm where it binds and stabilizes SNAI2 and CA9 mRNAs, in cooperation with the mRNA stabilizing protein HuR. We also provide evidence that the post-transcriptional activity of cytoplasmic beta-catenin operates under normoxia in basal-like/triple-negative breast cancer cells, where the beta-catenin knockdown suppresses the stem cell phenotype in vitro and tumor growth in vivo. In such cells, we unravel the generalized involvement of the beta-catenin-driven machinery in the stabilization of EGF-induced mRNAs, including the cancer stem cell regulator IL6. Our study highlights the crucial role of post-transcriptional mechanisms in the maintenance/acquisition of cancer stem cell features and suggests that the hindrance of cytoplasmic beta-catenin function may represent an unprecedented strategy for targeting breast cancer stem/basal-like cells

HPV DNA Associates With Breast Cancer Malignancy and It Is Transferred to Breast Cancer Stromal Cells by Extracellular Vesicles

A causal link between Human Papillomavirus (HPV) and breast cancer (BC) remains controversial. In spite of this, the observation that HPV DNA is over-represented in the Triple Negative (TN) BC has been reported. Here we remark the high prevalence of HPV DNA (44.4%) in aggressive BC subtypes (TN and HER2+) in a population of 273 Italian women and we convey the presence of HPV DNA in the epithelial and stromal compartments by in situ hybridization. As previously reported, we also found that serum derived-extracellular vesicles (EVs) from BC affected patients contain HPV DNA. Interestingly, in one TNBC patient, the same HPV DNA type was detected in the serum-derived EVs, cervical and BC tissue samples. Then, we report that HPV DNA can be transferred by EVs to recipient BC stromal cells that show an activated phenotype (e.g., CD44, IL6 expression) and an enhanced capability to sustain mammospheres (MS) formation. These data suggest that HPV DNA vehiculated by EVs is a potential trigger for BC niche aggressiveness