Clinical Research Directory

Routine Intraoperative White Test for Bile Leak Detection in Liver Resection: A Randomized Trial Protocol

Bile leakage (BL) remains one of the most frequent complications following liver resection and is associated with increased postoperative morbidity and mortality, higher reintervention rates, prolonged hospital stay, and increased healthcare costs. Effective intraoperative identification and closure of open bile ducts may reduce the risk of postoperative BL. The White Test, which involves retrograde injection of a lipid emulsion into the biliary tree, enables active detection of bile leaks during surgery; however, its routine use has not been established in randomized clinical trials across all types of liver resection. This is a single-center, prospective, randomized, parallel-group, single-blinded superiority trial designed to evaluate the effectiveness of routine intraoperative use of the White Test compared with standard intraoperative bile leak detection using a white gauze test. Adult patients undergoing elective liver resection (major or minor, including both anatomic and non-anatomic resections) who meet eligibility criteria will be enrolled after providing written informed consent. Participants will be randomized in a 1:1 ratio to either the intervention group (White Test) or the control group (standard gauze test), using stratified block randomization according to the type of resection (major vs minor). Allocation will be concealed using sequentially numbered, opaque, sealed envelopes. Patients will remain blinded to group assignment, while the operating surgeon cannot be blinded due to the nature of the intervention. In the intervention group, following completion of liver parenchymal transection and achievement of hemostasis, the cystic duct stump will be identified and cannulated. The distal bile duct will be temporarily occluded, and 10-20 mL of lipid emulsion will be injected retrogradely into the biliary tree. The transection surface will be inspected for leakage of the white emulsion. Identified leaks will be managed by ligation or suturing, and the test may be repeated until no further leakage is observed. In the control group, bile leak detection will be performed by applying sterile white gauze to the transection surface with visual inspection, followed by suturing of identified leaks as needed. All patients will have intra-abdominal drainage placed at the resection site. Drain fluid bilirubin concentration will be measured on postoperative day three. Patients will be followed for 30 days after surgery. The primary outcome is the incidence of postoperative bile leakage within 30 days, defined according to the International Study Group of Liver Surgery (ISGLS) criteria. Secondary outcomes include severity of bile leakage (ISGLS grades A-C), postoperative morbidity (Clavien-Dindo classification), need for postoperative interventions (endoscopic, radiological, or surgical), intensive care unit (ICU) admission and length of ICU stay, and total hospital length of stay. The primary analysis will follow the intention-to-treat principle and will be performed separately within strata defined by resection type (major vs minor). Secondary and subgroup analyses will be considered exploratory. No formal interim analysis is planned; however, patient safety will be continuously monitored throughout the study. The results of this trial are expected to clarify the role of routine intraoperative White Test in liver surgery and its potential to reduce postoperative bile leakage and improve clinical outcomes.

Safety of HRX215 in Patients After Minor and Major Liver Resection

The goal of this clinical trial is to learn if HRX215 is safe and tolerable in adults who have undergone surgical removal of metastatic tumor(s) due to colorectal carcinoma in the liver. The main question it aims to answer are: 1. to learn about the safety of HRX215 2. to learn about how the body absorbs, distributes, and gets rid of HRX215 . Researchers will compare HRX215 to a placebo (a look-alike substance that contains no drug) to see what medical problems participants have when taking HRX215. Participants will: Take HRX215 or a placebo twice a day for 28 days Daily visits for 7 days for checkups and tests which may either be in the hospital or outpatient after 3 days. Clinic visits every two weeks for the next two visits. The visit at two weeks may be a home visit or clinic visit. Additional clinic visits 3 months and 6 months after the start of treatment

Italian Group of Regenerative and Occlusive Worldwide-used Techniques of Hepatic Hypertrophy

The goal of this national mutlticenter observational study is to learn and describe trends over time in the use of techniques for inducing hepatic hypertrophy in Italy. Patients will be treated according to the current clinical practice of the participating centers and will be observed from the moment of recruitment and throughout their stay. Information on vital status will be collected, as far as possible, for up to 5 years after surgery in order to record any events that occur in a timely manner. There are also plans to retrospectively collect data on patients who underwent hypertrophic techniques in the previous 10 years, in order to establish a historical cohort for each center that can be used for comparison with the prospective cohort.

The Use of Artificial Intelligence for the Prediction of Recurrence After Resection of Colorectal Liver Metastases

Colorectal cancer is the third most common cancer worldwide and the fourth most common cause of cancer-related death. Survival is primarily determined by stage of disease and the presence of metastases. The combination of chemotherapy and liver resection remains the treatment option with the highest survival benefit for patients with liver metastases from colorectal cancer, with surgery still being the only recognized potential curative treatment; surgical locoregional treatment can also be combined with thermal ablation to enhance the possibility of complete liver clearance. Despite significant improvements in prognosis, a large proportion of patients (almost half) will still experience recurrence following treatment. There is a clinical need to identify a priori patients who are different likely to develop disease recurrence after locoregional treatment (liver resection ± thermal ablation) and to respond differently to chemotherapy, in order to refine risk-based allocation of treatments and resources. Widespread digitalization of healthcare generates a large amount of data, and together with today accessible high-performance computing, artificial intelligence technologies can be applied to overcome the current limitations in estimating colorectal cancer liver metastases recurrence and response to locoregional and chemotherapy treatments, thus achieving better treatment allocation than current practice. All radiomic features can also help in training the neural network aimed at detecting liver metastases before they become visually detectable by the radiologist. Therefore, this study aims to evaluate whether a multifactorial machine learning model (including clinical and radiomic) can identify patients with colorectal cancer liver metastases with a high risk of progression after chemotherapy and recurrence after liver resection

Evaluation Of Liver Resection Using Harmonic Scalpel Versus Cavitron Ultrasonic Surgical Aspirator (CUSA).

Evaluation Of Liver Resection Using Harmonic Scalpel Versus Cavitron Ultrasonic Surgical Aspirator (CUSA) Introduction The mode of parenchymal transection in hepatic resection has been a topic of great debate for decades. Many resections have now evolved into laparoscopic , and robotic-assisted procedures to limit morbidity. Morbidity and mortality after hepatic resection has progressively improved over the years due to improved equipment, operative technique \[3\], and anesthetic management. Prior to 1980, mortality rates were reported to be in the 10-20% range with many deaths related to perioperative hemorrhage. Now perioperative mortality has dropped significantly to approximately 5%. The clamp-crush technique, first reported in 1974, has been used for decades and remains the standard means of parenchymal division for many surgeons. Control of intraoperative hemorrhage has been one of the principle technical problems in advancing liver surgery. Excess blood loss and intraoperative blood transfusions have been shown to be associated with increased perioperative mortality and morbidity including an increased rate of hepatocellular carcinoma recurrence . Transfusions are also associated with increased infections and with increased cost. Costs of blood transfusions were recently examined in surgical patients. Many devices are now available to surgeons for division of the liver parenchyma in both open and minimally invasive surgery including: the CUSA (Tyco Healthcare, Mansfield, MA), Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH, USA), Ligasure (Valley Lab, Tyco Healthcare, Boulder, CO, USA), Tissue Link (Salient Surgical Technologies, Portsmouth, NH), water-jet dissection, radiofrequency, microwave assisted resection, vascular staplers, and others In this study, we looked at the TissueLink bipolar sealer device that was used in combination with the CUSA in group 1 termed the CUSA/TissueLink group, and the Harmonic Scalpel in the group 2 termed Harmonic Scalpel/TissueLink. The TissueLink uses radiofrequency energy focused near the end of the device for electrocautery and a low volume saline drip that produces ohmic heat causing precoagulation of hepatic parenchyma. The saline keeps the temperature at or below 100 C to avoid eshcar formation ultimately helping prevent delayed biliary leak and hemorrhage. The hemostatic effects of TissueLink are a result of its disruption of the collagen in blood vessels causing closing of the lumen . The CUSA, a commonly used device in hepatic resection, was used in combination with the TissueLink in this study. We previously described this combination of devices reporting a shorter length of hospital stay, decreased operative time, and decreased intraoperative blood transfusion . CUSA uses ultrasonic energy to fragment and aspirate parenchymal tissue. This exposes biliary as well as vascular structures that may then be closed in a variety of ways at the surgeon's discretion. It allows for a precise transection plane allowing preservation of normal hepatic tissue . The Harmonic Scalpel, used in this study in combination with the TissueLink, utilizes ultrasonic vibration of two blades causing destruction of hydrogen bonds. This disruption of hydrogen bonds causes protein denaturization coagulating small vessels of 3 mm diameter. The parenchyma is also cut when the blades move in a saw-like fashion In this study, we evaluated the safety and efficacy of two different techniques described above for the division of the hepatic parenchyma in order to improve perioperative outcomes.

Preoperative Anemia Affected to Postoperative Outcomes in Liver Resection

To assess the impact of preoperative anemia on postoperative outcomes in patients undergoing liver resection

Stroke Volume Variation Versus Central Venous Pressure Guidance for Reducing Perioperative Blood Loss During Open Liver Resection

Liver resection is a major surgery that can be associated with significant intraoperative blood loss and blood transfusion. Among high-volume centers, median intraoperative blood loss ranges between 300-800 ml. Excessive blood loss is a strong independent predictor of worsened postoperative outcomes, increasing morbidity and mortality rates by 20%-35%. Additionally, perioperative allogeneic blood transfusions are associated with deleterious outcomes, including tumor recurrence and increased rates of complications and death. The liver is a highly vascular organ with minimal vascular resistance, receiving up to 25% of cardiac output and pooling 20% of the splanchnic blood. Hepatic veins are a common source of venous hemorrhage. The pressure in the hepatic veins is directly correlated with the pressure in the vena cava and reducing cardiac preload results in decreased hepatic vein congestion. Therefore, low central venous pressure anesthesia (typically below 5 mmHg) can reduce the pressure gradient for retrograde venous bleeding, facilitate the outflow of blood from hepatic veins, and decrease blood volume and pressure in the liver. This anesthetic method is the standard technique to minimize blood loss during liver resection. Central venous pressure was the static parameter used to indicate the right ventricular end-diastolic volume index (RVEDI) and was believed to be correlated with volume status. Despite this, central venous pressure did not reliably predict preload responsiveness due to the curvilinear shape of the ventricular pressure-volume curve, which indicates a poor relationship between ventricular filling pressure and volume. Additionally, the placement of a central venous catheter could lead to serious complications such as arterial cannulation, pneumothorax, and infection. Arterial waveform analysis is dynamic hemodynamic monitoring based on the interaction between the heart and lungs in patients with mechanical ventilation. Stroke volume variation (SVV) is one aspect of arterial pressure waveform analysis and is a less invasive alternative technique for guiding preload status and fluid management in patients undergoing major abdominal surgery. In liver resection, several anesthetic methods are used to achieve low central venous pressure (CVP \< 5 mmHg) during the liver parenchymal dissection phase. These methods include intraoperative volume restriction, administration of venodilators or vasodilators, the use of forced diuresis with furosemide, and the implementation of hypovolemic phlebotomy. As mentioned, central venous pressure is a static hemodynamic monitoring parameter and poorly correlates with volume status. Recently, stroke volume variation has been recognized as a good parameter to predict volume status and fluid responsiveness in patients undergoing liver resection. However, no previous publications have studied the efficacy of stroke volume variation monitoring compared with central venous pressure monitoring to reduce perioperative blood loss during open liver resection. The study aimed to compare the efficacy of maintaining high stroke volume variation versus low central venous pressure in reducing perioperative blood loss during the liver transection phase in open liver resection.

Retrospective Clinical Validation of HepatoPredict

HepatoPredict is an innovative prognostic tool to support hepatologists, hepatobiliary surgeons and multidisciplinary teams in deciding on the best therapeutical approach for a patient with Hepatocellular Carcinoma, the most common type of primary liver cancer. HepatoPredict is a laboratory test that analyses a molecular signature from a small tumour sample and combines this information with details from imaging tests, such as the number of nodules and their size. Using a computational model, HepatoPredict determines whether a patient is likely to remain disease-free after hepatic surgery (good prognosis) or if there is a higher chance of the tumour returning (bad prognosis). Current selection criteria to assess the eligibility of patients with Hepatocellular Carcinoma for liver transplantation present several problems, including: 1. selection of patients that will not benefit from a transplant. This could be due to recurrence of cancer or early death from another cause. 2. exclusion of patients who could benefit from a liver transplant but are currently not eligible; 3. increased tumor recurrence rates. Thus, improved tools that predict the likelihood of cancer coming back are needed to better assess if a patient will benefit from hepatic surgery. This will allow better use of organs, waiting list times, and improve ways of identifying the most appropriate treatments for individual patients. HepatoPredict accurately selects patients for hepatic surgery, outperforming conventional clinical criteria. In previous retrospective studies, HepatoPredict predicted successful surgery outcomes in patients who were not eligible by currently used criteria. This study aims to retrospectively validate the prognostic tool HepatoPredict in assessing how well a patient with Hepatocellular Carcinoma performed considering recurrence-free survival (no cancer recurrence) and overall survival after 5 years follow-up after liver surgery or liver transplantation.