Assessing the effective connectivity of premotor areas during real vs imagined grasping: a DCM-PEB approach

The parieto-frontal circuit underlying grasping, which requires the serial involvement of the anterior intraparietal area (aIPs) and the ventral premotor cortex (PMv), has been recently extended enlightening the role of the dorsal premotor cortex (PMd). The supplementary motor area (SMA) has been also suggested to encode grip force for grasping actions; furthermore, both PMd and SMA are known to play a crucial role in motor imagery. Here, we aimed at assessing the dynamic couplings between left aIPs, PMv, PMd, SMA and primary motor cortex (M1) by comparing executed and imagined right-hand grasping, using Dynamic Causal Modelling (DCM) and Parametrical Empirical Bayes (PEB) analyses. 24 subjects underwent an fMRI exam (3T) during which they were asked to perform or imagine a grasping movement visually cued by photographs of commonly used objects. We tested whether the two conditions a) exert a modulatory effect on both forward and feedback couplings among our areas of interest, and b) differ in terms of strength and sign of these parameters. Results of the real condition confirmed the serial involvement of aIPs, PMv and M1. PMv also exerted a positive influence on PMd and SMA, but received an inhibitory feedback only from PMd. Our results suggest that a general motor program for grasping is planned by the aIPs-PMv circuit; then, PMd and SMA encode high-level features of the movement. During imagery, the connection strength from aIPs to PMv was weaker and the information flow stopped in PMv; thus, a less complex motor program was planned. Moreover, results suggest that SMA and PMd cooperate to prevent motor execution. In conclusion, the comparison between execution and imagery reveals that during grasping premotor areas dynamically interplay in different ways, depending on task demands

Neural representations underlying mental imagery as unveiled by representation similarity analysis

It is commonly acknowledged that visual imagery and perception rely on the same content-dependent brain areas in the high-level visual cortex (HVC). However, the way in which our brain processes and organizes previous acquired knowledge to allow the generation of mental images is still a matter of debate. Here, we performed a representation similarity analysis of three previous fMRI experiments conducted in our laboratory to characterize the neural representation underlying imagery and perception of objects, buildings and faces and to disclose possible dissimilarities in the neural structure of such representations. To this aim, we built representational dissimilarity matrices (RDMs) by computing multivariate distances between the activity patterns associated with each pair of stimuli in the content-dependent areas of the HVC and HC. We found that spatial information is widely coded in the HVC during perception (i.e. RSC, PPA and OPA) and imagery (OPA and PPA). Also, visual information seems to be coded in both preferred and non-preferred regions of the HVC, supporting a distributed view of encoding. Overall, the present results shed light upon the spatial coding of imagined and perceived exemplars in the HVC

Tailored treatment for signet ring cell gastric cancer

Gastric cancer with Laur\ue8n diffuse types is increasing in the West. The raising trend is more evident when considering signet ring cells (SRC) histology. However, to control the biologic potential of this GC subtype, some hypotheses of tailored therapeutic strategies for SRC cancers have been made. A review of the literature was performed using the key words "signet ring cells" AND "gastric cancer". Results of literature review were descriptively reported. Endoscopic submucosal dissection (ESD), according to the Japanese extended criteria, could be a therapeutic option for early SRC tumours. However, according to the evidences from more recent studies, indications for ESD to these tumours types should be carefully considered. Concerning the optimal surgical treatment, considering the high lymphotropism and infiltrating behaviour of SRC histotype, the extension of gastric resection should be wider than for intestinal type cancer and laparoscopic surgery should be performed carefully. Moreover, D3 lymphadenectomy could provide a benefit in diffuse-type and SRC histology. The role of surgery in gastric cancer with peritoneal carcinomatosis is still debated and studies on this topic should stratify the good results according to GC histotype. Finally, despite the evidences of chemoresistance in SRC, ongoing randomized trials suggest that multimodal therapy could be the best treatment. Based on the assumption that SRC tumours have specific features, they deserve a specific multimodal treatment. However, a preliminary step to generate strong evidences in this field is the standardization of terminology used to define signet ring cells carcinoma

Acute bleeding obstruction pancreatitis after Roux-en-Y anastomosis in total gastrectomy: a single center experience

Anastomotic intraluminal bleeding is a well-known complication after total gastrectomy. Nevertheless, few data are published on acute bleeding obstruction pancreatitis (BOP) due to a bleeding from the jejunojejunostomy (JJ). In this paper we describe our experience. A total of 140 gastrectomies for EGJ cancer were performed in our Institute from January 2012 to January 2017. All reconstructions were performed with a Roux-en-Y anastomosis: a mechanical end-to-side esophago-jejunostomy and a mechanical end-to-side JJ. Three patients suffered from a bleeding at the JJ with a consequent BOP. We analyzed the time of diagnosis, the treatment and the outcomes. The three patients presented anemia at the laboratory findings on postoperative day (POD) 1. In patient I laboratory findings of acute pancreatitis were found in POD 2. CT scan was performed and showed signs of BOP. Endoscopic treatment was tried without success. Therefore, patient underwent surgery: JJ take down, bleeding control and anastomosis rebuild were performed. In spite of this the patient died of MOF in POD 4. Patient II had a persistent anemia treated with blood transfusions until POD 3, when laboratory tests showed increased lipase and bilirubin levels. Patient was successfully treated with endoscopy but several blood transfusions and a prolonged recovery were necessary. Patient III had laboratory findings of acute pancreatitis on POD 1. Immediate surgery was performed and patient was discharged on POD 9 without sequelae. BOP is a rare but deadly complication after Roux-en-Y anastomosis. An early diagnosis and an aggressive treatment seem to improve the outcome

Primary Tumor Resection for Metastatic Colorectal, Gastric and Pancreatic Cancer Patients: In Search of Scientific Evidence to Inform Clinical Practice

The management of the primary tumor in metastatic colorectal, gastric and pancreatic cancer patients may be challenging. Indeed, primary tumor progression could be associated with severe symptoms, compromising the quality of life and the feasibility of effective systemic therapy, and might result in life-threatening complications. While retrospective series have suggested that surgery on the primary tumor may confer a survival advantage even in asymptomatic patients, randomized trials seem not to definitively support this hypothesis. We discuss the evidence for and against primary tumor resection for patients with metastatic gastrointestinal (colorectal, gastric and pancreatic) cancers treated with systemic therapies and put in context the pros and cons of the onco-surgical approach in the time of precision oncology. We also evaluate current ongoing trials on this topic, anticipating how these will influence both research and everyday practice

Multigene panel testing increases the number of loci associated with gastric cancer predisposition

The main gene involved in gastric cancer (GC) predisposition is CDH1, the pathogenic variants of which are associated with diffuse-type gastric cancer (DGC) and lobular breast cancer (LBC). CDH1 only explains a fraction (10–50%) of patients suspected of DGC/LBC genetic predisposition. To identify novel susceptibility genes, thus improving the management of families at risk, we performed a multigene panel testing on selected patients. We searched for germline pathogenic variants in 94 cancer-related genes in 96 GC or LBC Italian patients with early-onset and/or family history of GC. We found CDH1 pathogenic variants in 10.4% of patients. In 11.5% of cases, we identified loss-of-function variants in BRCA1, BRCA2, PALB2, and ATM breast/ovarian cancer susceptibility genes, as well as in MSH2, PMS2, BMPR1A, PRF1, and BLM genes. In 78.1% of patients, we did not find any variants with clear-cut clinical significance; however, 37.3% of these cases harbored rare missense variants predicted to be damaging by bioinformatics tools. Multigene panel testing decreased the number of patients that would have otherwise remained genetically unexplained. Besides CDH1, our results demonstrated that GC pathogenic variants are distributed across a number of susceptibility genes and reinforced the emerging link between gastric and breast cancer predisposition.This research was supported by the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, by the Italian Ministry of Education, University and Research (MIUR)—Dipartimenti di Eccellenza Program (2018–2022)—Department of Biology and Biotechnology L. Spallanzani, University of Pavia, and by the Dunia Beam Erasmus Mundus project (fellowship to R.A.K.)

Nanoscale transient magnetization gratings excited and probed by femtosecond extreme ultraviolet pulses

We utilize coherent femtosecond extreme ultraviolet (EUV) pulses derived from a free electron laser (FEL) to generate transient periodic magnetization patterns with periods as short as 44 nm. Combining spatially periodic excitation with resonant probing at the dichroic M-edge of cobalt allows us to create and probe transient gratings of electronic and magnetic excitations in a CoGd alloy. In a demagnetized sample, we observe an electronic excitation with 50 fs rise time close to the FEL pulse duration and ~0.5 ps decay time within the range for the electron-phonon relaxation in metals. When the experiment is performed on a sample magnetized to saturation in an external field, we observe a magnetization grating, which appears on a sub-picosecond time scale as the sample is demagnetized at the maxima of the EUV intensity and then decays on the time scale of tens of picoseconds via thermal diffusion. The described approach opens prospects for studying dynamics of ultrafast magnetic phenomena on nanometer length scales

A pragmatic approach improves the clinical management of stage IV gastric cancer: Comparison between the Meta-Gastro results and the GIRCG's retrospective series

Introduction: The Italian Research Group for Gastric Cancer developed a prospective database about stage IV gastric cancer, to evaluate how a pragmatic attitude impacts the management of these patients. Materials and methods: We prospectively collected data about metastatic gastric cancer patients thanks to cooperation between radiologists, oncologists and surgeons and we analyzed survival and prognostic factors, comparing the results to those obtained in our retrospective study. Results: Three-hundred and eighty-three patients were enrolled from 2018 to September 2022. We observed a higher percentage of laparoscopic exploration with peritoneal lavage in the prospective cohort. In the registry only 3.6 % of patients was submitted to surgery without associated chemotherapy, while in the retrospective population 44.3 % of patients were operated on without any chemotherapy. At univariate and multivariate analyses, the different metastatic sites did not show any survival differences among each other (OS 20.0 vs 16.10 vs 16.7 months for lymphnodal, peritoneal and hepatic metastases, respectively), while the number of metastatic sites and the type of treatment showed a statistical significance (OS 16,7 vs 13,0 vs 4,5 months for 1, 2 and 3 different metastatic sites respectively, p < 0.001; 24,2 vs 12,0 vs 2,5 months for surgery with/without chemotherapy, chemotherapy alone and best supportive treatment respectively, p < 0.001). Conclusions: Our data highlight that the different metastatic sites did not show different survivals, but survival is worse in case of multiple localization. In patients where a curative resection can be achieved, acceptable survival rates are possible. A better diagnostic workup and a more accurate staging impact favorably upon survival

International External Validation of Risk Prediction Model of 90-Day Mortality after Gastrectomy for Cancer Using Machine Learning

Background: Radical gastrectomy remains the main treatment for gastric cancer, despite its high mortality. A clinical predictive model of 90-day mortality (90DM) risk after gastric cancer surgery based on the Spanish EURECCA registry database was developed using a matching learning algorithm. We performed an external validation of this model based on data from an international multicenter cohort of patients. Methods: A cohort of patients from the European GASTRODATA database was selected. Demographic, clinical, and treatment variables in the original and validation cohorts were compared. The performance of the model was evaluated using the area under the curve (AUC) for a random forest model. Results: The validation cohort included 2546 patients from 24 European hospitals. The advanced clinical T- and N-category, neoadjuvant therapy, open procedures, total gastrectomy rates, and mean volume of the centers were significantly higher in the validation cohort. The 90DM rate was also higher in the validation cohort (5.6%) vs. the original cohort (3.7%). The AUC in the validation model was 0.716. Conclusion: The externally validated model for predicting the 90DM risk in gastric cancer patients undergoing gastrectomy with curative intent continues to be as useful as the original model in clinical practice.</p

European clinical practice guidelines for the definition, diagnosis, and treatment of oligometastatic esophagogastric cancer (OMEC-4)

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI &gt; 2 years, upfront local treatment is additionally recommended. Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.</p