Clinical Research Directory

Implementation of a Pain Management Plan in Major Open Abdominal Surgeries.

Introduction: Major abdominal surgery encompasses a broad range of surgical procedures in heterogeneous patient populations.Management of postoperative pain has received keen attention in recent years with considerable concurrent advancement in the field.Despite this improvement,postoperative pain continues to be a challenge since suboptimal postoperative pain control is a risk factor for persistent surgical pain,increased morbidity,poorer functional recovery and reduced quality of life.Therefore,analgesic strategies should regard patients' factors as well as surgical procedures peculiarities.Since efforts are made throughout the years and are of utmost importance as numerous analgesic options exist for the effective pain control after abdominal surgeries including multiple classes of drugs and routes of administration(i.e.parenteral,regional,neuraxia.)In the context of the current surgical environment where improvement has been made,emphasis is placed on precision,minimizing trauma and improving the outcome.The choice of postoperative pain analgesic modality,is at the discretion of the primary anaesthesiologist and the choice depends upon the plan favored by him/her as well as the availability of drugs and equipment.Continuous re-evaluation of analgesic strategies is a necessary step toward establishing a better pain management plan in major abdominal surgeries and to design guidelines to improve our clinical approach. Study Objective: The target of the study is to compare the outcome of the selected analgesic combination of local anaesthetic and opioid(ropivacaine+fentanyl or ropivacaine +morphine)for postoperative continuous infusion,aiming to relief successfully the pain,on patients undergoing major abdominal surgeries based on hemodynamic and clinical findings. The study aims to highlight the positive impact of the chosen analgesic combination during the intraoperative period,the postoperative recovery period and also during the follow up periods in terms of physical function,pain intensity during activity,adverse effects and self efficacy. Methods: The study is prospective,comparative aiming to identify the pain management agents that will provide the best postoperative relief in order to be established and used as a primary choice to patients undergoing major open abdominal surgeries .All patients included will receive the same analgesic technique(epidural)chosen preoperatively by the anaesthesiologist in charge.All study participants are informed in detail and written informed consent is obtained.The study is in accordance with the regulations of the Declaration of Helsinki on human studies and the Greek legislation. The investigators will study 58 patients,equally divided into two groups, aged 18-80 years,administered to Evangelismos General hospital,Athens-Greece, for elective open abdominal surgeries. In group A(p:29),the investigators will administer for postoperative pain relief - Ropivacaine 200 ml/400 mg + Fentanyl for continuous epidural infusion for the first 5 days.The infusion will start 2 hours before the end of the operation and before the admission to the intensive care unit. In group B(p:29),the investigators will administer for postoperative pain relief Ropivacaine 200ml/400mg + Morphine for continuous epidural infusion for the first 5 days.The infusion will start 2 hours before the end of the operation and before the admission to the intensive care unit.

A Beta-only IL-2 ImmunoTherapY Study

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.

Targeted Nutritional Intervention (HMB, Arginine, Glutamine) in Patients With Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with cancer cachexia, a condition characterized by progressive loss of skeletal muscle mass and strength driven by systemic inflammation. Recent evidence suggests that chemotherapy and tumor-related inflammation disrupt the gut-muscle axis, leading to increased intestinal permeability and bacterial imbalance (dysbiosis), which further worsen muscle loss. The purpose of this pilot study is to evaluate whether an early, targeted nutritional supplement containing beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-glutamine can preserve or increase skeletal muscle mass in patients with locally advanced pancreatic ductal adenocarcinoma starting systemic chemotherapy. Participants will be randomly assigned to one of two groups: * Experimental group: receives standard dietary counseling plus an oral nutritional supplement (Abound, containing beta-hydroxy-beta-methylbutyrate, L-arginine, and L-glutamine) twice daily for 60 days, starting 7 to 10 days before the first cycle of chemotherapy. * Control group: receives standard dietary counseling alone. The total study participation for each patient is 60 days, during which changes in muscle mass, muscle quality, physical function, quality of life, and blood and stool biomarkers will be evaluated.

Superb Microvascular Imaging (SMI) and Two-Dimensional Endoscopic Ultrasound Guided Shear Wave Elastography (2D-SWE-EUS) in Differential Diagnosis of Pancreatic Adenocarcinoma (PA) From Other Pancreatic Solid Lesions (PSLs) and Pancreatic neuroendocrinE Tumors (pNETs) Malignancy

Pancreatic adenocarcinoma (PA) is the most common tumor of the pancreas. Given its poor prognosis and the major therapeutic consequences, the discrimination between PA and other pancreatic solid lesions is mandatory. Endoscopic ultrasound (EUS) is admitted as the most sensitive imaging procedure for the detection and characterization of pancreatic tumors. Over the past 30 years, EUS-guided tissue acquisition (EUS-TA), or more recently fine needle biopsy (EUS-FNB), has demonstrated its efficiency for tissue sampling and remains the gold standard for the pathologic diagnosis of pancreatic lesions. The assessment of pancreatic tumor enhancement using ultrasound contrast agents (UCAs) in real time with imaging specific methods seems useful to improve their characterization either by contrast-enhanced EUS (CE-EUS) or, more recently, by contrast-harmonic EUS (CH-EUS). CH-EUS was already demonstrated useful to differentiate pancreatic adenocarcinoma from other pancreatic lesions. EUS-Elastography (EUS-E) is another EUS image enhancement technique, which rational based on the difference in elasticity between the tissues. There are two types of elastographies: strain elastography (SE) and shear wave elastography (SWE). SE has proved useful for the characterization of pancreatic lesions and lymph nodes. However, this technique was demonstrated difficult to perform with adequate accuracy and reproducibility for pancreatic lesions and have many limitations. In some recent publications SWE was demonstrated moderate reliability. Pancreatic neuroendocrine tumors (pNETs) are rare tumors, but according to the last epidemiological data, their incidence and prevalence are steadily rising. Surgical resection is generally performed for pNETs due to their malignant potential. However, with increasing use of high-resolution conventional imaging, the significant incidence of small (≤ 2 cm) pancreatic neuroendocrine incidentaloma (pNET) has risen in recent decades. EUS is recognized as the most sensitive procedure for the detection and characterization of pNETs. Overall sensitivity of EUS-TA for the diagnosis of pNETs is high, reaching 95.1% in recently published study, appearing higher in small lesions (≤ 20 mm) than in large lesions (\> 20 mm). The overall concordance rate for EUS-TA and surgical specimens grading varies from 58% to 86.4% and is higher for lesions ≤ 10 mm, 10-20 mm, comparing to lesions \> 20 mm. These results confirm the risk of under or over-grading of pNETs on the EUS-TA specimen, independently of the needle size which used for the TA. CH-EUS was also demonstrated accurate in the prediction of pNETs malignancy and useful for decision-making management of these tumors. Hypothesis Two new image enhancement EUS technologies were recently developed, able to assess precisely tumor microvascular density and the stiffness of pancreatic lesions, that is correlated to tumor's stroma fibrosis, and thus help to characterize and predict the malignancy, and accordingly, the management of the pancreatic solid lesions. It's particularly useful in overcoming EUS false-negative cases of PA and small pNETs malignancy diagnosis. Superb Microvascular Imaging (SMI) is a novel doppler technique that enhances the range of visible blood flow, by revealing low velocity microvascular flow, enabling the capture of a higher-quality microvascular flow images. Based on the same principle as CH-EUS, which assesses tumor microvascularization, this technique is expected to be also useful for the PSLs malignancy diagnosis. Shear Wave Elastography (SWE) relies on the properties of shear-wave propagation to offer an advanced assessment of their velocity

Exercise to Improve Outcomes in Pancreatic Cancer

Pancreatic cancer surgery (Whipple's procedure) is a major operation that can lead to reduced physical fitness, delayed recovery, and difficulty starting chemotherapy after surgery. Exercise before and after surgery may help improve recovery, but it is not known whether a personalised exercise programme delivered throughout the surgical pathway is practical or acceptable for patients. The Exercise to Improve Outcomes in Pancreatic Cancer (ExO-PanC) study is a single-arm feasibility study that will recruit adults with suspected pancreatic ductal adenocarcinoma who are scheduled to undergo Whipple's procedure. Participants will receive an individualised exercise programme before surgery, during their hospital stay, and after discharge until the start of adjuvant chemotherapy. The programme will include aerobic exercise and resistance training prescribed according to each participant's fitness level. The primary objective is to determine whether this exercise programme is feasible by assessing recruitment, participant adherence, compliance with the prescribed exercise programme, and retention. Secondary exploratory objectives include evaluating surgical complications, initiation of adjuvant chemotherapy, physical fitness, quality of life, nutritional status, and blood, stool, and tumour biomarkers associated with clinical outcomes. Findings from this feasibility study will inform the design of a future multicentre randomised controlled trial evaluating the effectiveness of the ExO-PanC programme.

A Trial Using Transcriptomic Signatures to Personalize Neoadjuvant Chemotherapy (NAC) for Patients With Resectable Borderline Pancreatic Adenocarcinoma (PDAC)

Pancreatic cancer exhibits significant heterogeneity, which poses a major challenge in selecting the best treatment for patients from the very beginning of care. Modern oncology recognizes the use of companion biomarkers to guide targeted therapy or immune checkpoint inhibitors. However, with regard to chemotherapy-which has long been the cornerstone of cancer treatment and remains crucial for most cancers-few predictive tests are available to guide the choice between monotherapy and combination chemotherapy. Patients included in the PRODIGE 104 B - NEOPREDICT study will be those for whom the GEM transcriptomic signature is negative. This population will be treated according to the standard strategy and will be followed clinically and biologically to describe and identify the characteristics specific to this subgroup, and to compare the usual prognostic factors of this population with those of the GEM-positive population included in the parallel PRODIGE 104 A - NEOPREDICT study