Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. IMPACT AND IMPLICATIONS: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699.

Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania: A prospective, cohort, multicentre study of 9000 patients.

BACKGROUND: The epidemiology of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be different worldwide. Despite similarities in medicine quality and formation, there are also significant differences concerning healthcare and ICU organisation, staffing, financial resources and population compliance and adherence. Large cohort data of critically ill patients from Central and Eastern Europe are also lacking. OBJECTIVES: The study objectives were to describe the clinical characteristics of patients admitted to Romanian ICUs with SARS-CoV-2 infection and to identify the factors associated with ICU mortality. DESIGN: Prospective, cohort, observational study. SETTING: National recruitment, multicentre study, between March 2020 to March 2021. PATIENTS: All patients with SARS-CoV-2 infection admitted to Romanian ICUs were eligible. There were no exclusion criteria. INTERVENTION: None. MAIN OUTCOME MEASURE: ICU mortality. RESULTS: The statistical analysis included 9058 patients with definitive ICU outcome. The multivariable mixed effects logistic regression model found that age [odds ratio (OR) 1.27; 95% confidence interval (CI), 1.23 to 1.31], male gender (OR 1.21; 95% CI 1.05 to 1.4), medical history of neoplasia (OR 1.74; 95% CI, 1.36 to 2.22), chronic kidney disease (OR 1.54; 95% CI, 1.27 to 1.88), type II diabetes (OR 1.23; 95% CI, 1.06 to 1.43), chronic heart failure (OR 1.24; 95% CI, 1.03 to 1.49), dyspnoea (OR 1.3; 95% CI, 1.1 to 1.5), SpO2 less than 90% (OR 3; 95% CI, 2.5 to 3.5), admission SOFA score (OR 1.07; 95% CI, 1.05 to 1.09), acute respiratory distress syndrome (ARDS) on ICU admission (OR 1.35; 95% CI, 1.1 to 1.63) and the need for noninvasive (OR 1.8, 95% CI, 1.5 to 1.22) or invasive ventilation (OR 28; 95% CI, 22 to 35) and neuromuscular blockade (OR 3.5; 95% CI, 2.6 to 4.8), were associated with larger ICU mortality.Higher GCS on admission (OR 0.81; 95% CI, 0.79 to 0.83), treatment with hydroxychloroquine (OR 0.78; 95% CI, 0.64 to 0.95) and tocilizumab (OR 0.58; 95% CI, 0.48 to 0.71) were inversely associated with ICU mortality. CONCLUSION: The SARS-CoV-2 critically ill Romanian patients share common personal and clinical characteristics with published European cohorts. Public health measures and vaccination campaign should focus on patients at risk.

Nociception Control of Bilateral Single-Shot Erector Spinae Plane Block Compared to No Block in Open Heart Surgery-A Post Hoc Analysis of the NESP Randomized Controlled Clinical Trial.

Background and Objectives: The erector spinae plane block (ESPB) is an analgesic adjunct demonstrated to reduce intraoperative opioid consumption within a Nociception Level (NOL) index-directed anesthetic protocol. We aimed to examine the ESPB effect on the quality of intraoperative nociception control evaluated with the NOL index. Materials and Methods: This is a post hoc analysis of the NESP (Nociception Level Index-Directed Erector Spinae Plane Block in Open Heart Surgery) randomized controlled trial. Eighty-five adult patients undergoing on-pump cardiac surgery were allocated to group 1 (Control, n = 43) and group 2 (ESPB, n = 42). Both groups received general anesthesia. Preoperatively, group 2 received bilateral single-shot ESPB (1.5 mg/kg/side 0.5% ropivacaine mixed with dexamethasone 8 mg/20 mL). Until cardiopulmonary bypass (CPB) was initiated, fentanyl administration was individualized using the NOL index. The NOL index was compared at five time points: pre-incision (T1), post-incision (T2), pre-sternotomy (T3), post-sternotomy (T4), and pre-CPB (T5). On a scale from 0 (no nociception) to 100 (extreme nociception), a NOL index > 25 was considered an inadequate response to noxious stimuli. Results: The average NOL index across the five time points in group 2 to group 1 was 12.78 ± 0.8 vs. 24.18 ± 0.79 (p < 0.001). The NOL index was significantly lower in the ESPB-to-Control group at T2 (12.95 ± 1.49 vs. 35.97 ± 1.47), T3 (13.28 ± 1.49 vs. 24.44 ± 1.47), and T4 (15.52 ± 1.49 vs. 34.39 ± 1.47) (p < 0.001) but not at T1 and T5. Compared to controls, significantly fewer ESPB patients reached a NOL index > 25 at T2 (4.7% vs. 79%), T3 (0% vs. 37.2%), and T4 (7.1% vs. 79%) (p < 0.001). Conclusions: The addition of bilateral single-shot ESPB to general anesthesia during cardiac surgery improved the quality of intraoperative nociception control according to a NOL index-based evaluation.

The effect of a viscoelastic-guided bleeding algorithm implementation on blood products use in adult liver transplant patients. A propensity score-matched before-after study.

BACKGROUND: Perioperative blood products transfusion is correlated with increased morbidity and mortality in liver transplantation (LTx). The objectives of our study are to assess the effect of a standardized viscoelastic test (VET)-guided bleeding management algorithm implementation on intraoperative bleeding, allogenic blood products and factor concentrates requirements and on early postoperative complications in LTx. METHODS: Retrospective before-after study comparing two matched cohorts of patients undergoing LTx before (control cohort) and after (intervention cohort) the implementation of a VET-based bleeding algorithm in a single center academic hospital. RESULTS: After propensity score matching, we included 94 patients in each cohort. Patients in intervention cohort received significantly less blood products, fresh frozen plasma (FFP), and cryoprecipitate (p < 0.001 for each), while the amount of fibrinogen concentrate used was significantly higher (p < 0.001). Postoperatively, intervention cohort patients had significantly lower postoperative hemoglobin and fibrinogen levels and longer prothrombin time compared to control cohort. There were no significant differences in red blood cells transfusions, intraoperative bleeding, early postoperative complications, and short term survival. CONCLUSIONS: The implementation of a VET-guided bleeding algorithm decreases allogenic blood products requirements, mainly FFP use and allows a more restrictive management of coagulopathy in patients with chronic liver disease undergoing LTx.

Lung mechanics during video-assisted abdominal surgery in Trendelenburg position: a cross-sectional propensity-matched comparison between classic laparoscopy and robotic-assisted surgery.

BACKGROUND: Video-assisted surgery has become an increasingly used surgical technique in patients undergoing major thoracic and abdominal surgery and is associated with significant perioperative respiratory and cardiovascular changes. The aim of this study was to investigate the effect of intraoperative pneumoperitoneum during video-assisted surgery on respiratory physiology in patients undergoing robotic-assisted surgery compared to patients undergoing classic laparoscopy in Trendelenburg position. METHODS: Twenty-five patients undergoing robotic-assisted surgery (RAS) were compared with twenty patients undergoing classic laparoscopy (LAS). Intraoperative ventilatory parameters (lung compliance and plateau airway pressure) were recorded at five specific timepoints: after induction of anesthesia, after carbon dioxide (CO2) insufflation, one-hour, and two-hours into surgery and at the end of surgery. At the same time, arterial and end-tidal CO2 values were noted and arterial to end-tidal CO2 gradient was calculated. RESULTS: We observed a statistically significant difference in plateau pressure between RAS and LAS at one-hour (26.2 ± 4.5 cmH2O vs. 20.2 ± 3.5 cmH2O, p = 0.05) and two-hour intervals (25.2 ± 5.7 cmH2O vs. 17.9 ± 3.1 cmH2O, p = 0.01) during surgery and at the end of surgery (19.9 ± 5.0 cmH2O vs. 17.0 ± 2.7 cmH2O, p = 0.02). Significant changes in lung compliance were also observed between groups at one-hour (28.2 ± 8.5 mL/cmH2O vs. 40.5 ± 13.9 mL/cmH2O, p = 0.01) and two-hour intervals (26.2 ± 7.8 mL/cmH2O vs. 54.6 ± 16.9 mL/cmH2O, p = 0.01) and at the end of surgery (36.3 ± 9.9 mL/cmH2O vs. 58.2 ± 21.3 mL/cmH2O, p = 0.01). At the end of surgery, plateau pressures remained higher than preoperative values in both groups, but lung compliance remained significantly lower than preoperative values only in patients undergoing RAS with a mean 24% change compared to 1.7% change in the LAS group (p = 0.01). We also noted a more significant arterial to end-tidal CO2 gradient in the RAS group compared to LAS group at one-hour (12.9 ± 4.5 mmHg vs. 7.4 ± 4.4 mmHg, p = 0.02) and two-hours interval (15.2 ± 4.5 mmHg vs. 7.7 ± 4.9 mmHg, p = 0.02), as well as at the end of surgery (11.0 ± 6.6 mmHg vs. 7.0 ± 4.6 mmHg, p = 0.03). CONCLUSION: Video-assisted surgery is associated with significant changes in lung mechanics after induction of pneumoperitoneum. The observed changes are more severe and longer-lasting in patients undergoing robotic-assisted surgery compared to classic laparoscopy.

Nociception Level Index-Directed Erector Spinae Plane Block in Open Heart Surgery: A Randomized Controlled Clinical Trial.

Background and Objectives: The erector spinae plane block (ESPB) is a multimodal opioid-sparing component, providing chest-wall analgesia of variable extent, duration, and intensity. The objective was to examine the ESPB effect on perioperative opioid usage and postoperative rehabilitation when used within a Nociception Level (NOL) index-directed anesthetic protocol. Materials and Methods: This prospective, randomized, controlled, open-label study was performed in adult patients undergoing on-pump cardiac surgery in a single tertiary hospital. Eighty-three adult patients who met eligibility criteria were randomly allocated to group 1 (Control, n = 43) and group 2 (ESPB, n = 40) and received general anesthesia with NOL index-directed fentanyl dosing. Preoperatively, group 2 also received bilateral single-shot ultrasound-guided ESPB (1.5 mg/kg/side 0.5% ropivacaine mixed with dexamethasone 8 mg/20 mL). Postoperatively, both groups received intravenous paracetamol (1 g every 6 h). Morphine (0.03 mg/kg) was administered for numeric rating scale (NRS) scores ≥4. Results: The median (IQR, 25th−75th percentiles) intraoperative fentanyl and 48 h morphine dose in group 2-to-group 1 were 1.2 (1.1−1.5) vs. 4.5 (3.8−5.5) µg·kg−1·h−1 (p < 0.001) and 22.1 (0−40.4) vs. 60.6 (40−95.7) µg/kg (p < 0.001). The median (IQR) time to extubation in group 2-to-group 1 was 90 (60−105) vs. 360 (285−510) min (p < 0.001). Two hours after ICU admission, 87.5% of ESPB patients were extubated compared to 0% of controls (p < 0.001), and 87.5% were weaned off norepinephrine compared to 46.5% of controls (p < 0.001). The median NRS scores at 0, 6, 12, 24, and 48 h after extubation were significantly decreased in group 2. There was no difference in opioid-related adverse events and length of stay. Conclusions: NOL index-directed ESPB reduced intraoperative fentanyl by 73.3% and 48 h morphine by 63.5%. It also hastened the extubation and liberation from vasopressor support and improved postoperative analgesia.

Parenchyma Sparing ALPPS Ultrasound Guided Partition Through Segment 4 to Maximize Resectability (with video).

Background: Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS). Materials and Methods: Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance. Results: Between April 2017 and April 2021, five patients with median age of 68 years (range: 66-78), four male and one female, underwent psALPPS for colorectal liver metastases (N=2), intrahepatic cholangiocarcinoma (N=2), and hepatocellular carcinoma (N=1). Standardized FLR (sFLR) for segments 2-3 before stage 1 surgery would have been a median of 11.6%. PsALPPS could double the sFLR at stage 1 resulting in an increase of ps-sFLR from a median of 22.7% (at stage 1) to 34.0% (at stage 2) after a median interstage interval of 15 days. All patients tolerated surgery well and no major complications were recorded. Conclusions: Applying the principles of parenchyma sparing surgery to ALPPS offers the advantage to maximize FLR and simultaneously reduce ischemic injury of segment 4 compared to conventional ALPPS. In this way, psALPPS may markedly increase resectability while reducing morbidity. Video: https://www.revistachirurgia.ro/pdfs/?EntryID=922974&art=2021-parenchyma-sparing-ALPPS-ultrasound-guided-partition.pdf

Parenchyma Sparing ALPPS - Ultrasound Guided Partition Through Segment 4 to Maximize Resectability (with video).

Background: Associating liver partition and portal vein ligation (ALPPS) has evolved as a treatment strategy for patients with liver tumors who are not amenable for upfront hepatectomy because of an insufficient future liver remnant (FLR). Aim of this study was to test the applicability of ultrasound guided parenchyma sparing surgery to ALPPS concept, by non-anatomically shifting the plane of transection in favor of FLR, resulting in a new technical variant of ALPPS, entitled parenchyma sparing ALPPS (psALPPS). Materials and Methods: Patients who could not safely undergo right trisectionectomy ALPPS because of insufficient FLR were considered eligible for psALPPS, consisting in liver partition through segment 4 using ultrasound guidance. Results: Between April 2017 and April 2021, five patients with median age of 68 years (range: 66-78), four male and one female, underwent psALPPS for colorectal liver metastases (N=2), intrahepatic cholangiocarcinoma (N=2), and hepatocellular carcinoma (N=1). Standardized FLR (sFLR) for segments 2-3 before stage 1 surgery would have been a median of 11.6%. PsALPPS could double the sFLR at stage 1 resulting in an increase of ps-sFLR from a median of 22.7% (at stage 1) to 34.0% (at stage 2) after a median interstage interval of 15 days. All patients tolerated surgery well and no major complications were recorded. Conclusions: Applying the principles of parenchyma sparing surgery to ALPPS offers the advantage to maximize FLR and simultaneously reduce ischemic injury of segment 4 compared to conventional ALPPS. In this way, psALPPS may markedly increase resectability while reducing morbidity. Video version: https://www.revistachirurgia.ro/pdfs/?EntryID=922974&art=2021-parenchyma-sparing-ALPPS-ultrasound-guided-partition.pdf

Aggressive surgical approach in patients with adrenal-only metastases from hepatocellular carcinoma enables higher survival rates than standard systemic therapy.

BACKGROUND: Although guidelines recommend systemic therapy even in patients with limited extrahepatic metastases from hepatocellular carcinoma (HCC), a few recent studies suggested a potential benefit for resection of extrahepatic metastases. However, the benefit of adrenal resection (AR) for adrenal-only metastases (AOM) from HCC was not proved yet. This is the first study to compare long-term outcomes of AR to those of sorafenib in patients with AOM from HCC. METHODS: The patients with adrenal metastases (AM) from HCC were identified from the electronic records of the institution between January 2002 and December 2018. Those who presented AM and other sites of extrahepatic disease were excluded. Furthermore, the patients with AOM who received other therapies than AR or sorafenib were excluded. RESULTS: A total of 34 patients with AM from HCC were treated. Out of these, 22 patients had AOM, 6 receiving other treatment than AR or sorafenib. Eventually, 8 patients with AOM underwent AR (AR group), while 8 patients were treated with sorafenib (SOR group). The baseline characteristics of the two groups were not significantly different in terms of age, sex, number and size of the primary tumor, timing of AM diagnosis, Child-Pugh and ECOG status. After a median follow-up of 15.5 months, in the AR group, the 1-, 3-, and 5-year overall survival rates (85.7%, 42.9%, and 0%, respectively) were significantly higher than those achieved in the SOR group (62.5%, 0% and 0% at 1-, 3- and 5-year, respectively) (P = 0.009). The median progression-free survival after AR (14 months) was significantly longer than that after sorafenib therapy (6 months, P = 0.002). CONCLUSIONS: In patients with AOM from HCC, AR was associated with significantly higher overall and progression-free survival rates than systemic therapy with sorafenib. These results could represent a starting-point for future phase II/III clinical trials.

Ultrasound-Guided Regional Anesthesia-Current Strategies for Enhanced Recovery after Cardiac Surgery.

With the advent of fast-track pathways after cardiac surgery, there has been a renewed interest in regional anesthesia due to its opioid-sparing effect. This paradigm shift, looking to improve resource allocation efficiency and hasten postoperative extubation and mobilization, has been pursued by nearly every specialty area in surgery. Safety concerns regarding the use of classical neuraxial techniques in anticoagulated patients have tempered the application of regional anesthesia in cardiac surgery. Recently described ultrasound-guided thoracic wall blocks have emerged as valuable alternatives to epidurals and landmark-driven paravertebral and intercostal blocks. These novel procedures enable safe, effective, opioid-free pain control. Although experience within this field is still at an early stage, available evidence indicates that their use is poised to grow and may become integral to enhanced recovery pathways for cardiac surgery patients.

Is Long-Term Survival in Metastases from Neuroendocrine Neoplasms Improved by Liver Resection?

Background and Objectives: Although many of the neuroendocrine neoplasms (NEN) have a typically prolonged natural history compared with other gastrointestinal tract cancers, at least 40% of patients develop liver metastases. This study aims to identify whether liver resection improves the overall survival of patients with liver metastases from NEN. Materials and Methods: We conducted a retrospective study at "Fundeni" Clinical Institute over a time period of 15 years; we thereby identified a series of 93 patients treated for NEN with liver metastases, which we further divided into 2 groups as follows: A (45 patients) had been subjected to liver resection complemented by systemic therapies, and B (48 patients) underwent systemic therapy alone. To reduce the patient selection bias we performed at first a propensity score matching. This was followed by a bootstrapping selection with Jackknife error correction, with the purpose of getting a statistically illustrative sample. Results: The overall survival of the matched virtual cohort under study was 41 months (95% CI 37-45). Group A virtual matched patients showed a higher survival rate (52 mo., 95% CI: 45-59) than B (31 mo., 95% CI: 27-35), (p < 0.001, Log-Rank test). Upon multivariate analysis, seven independent factors were identified to have an influence on survival: location (midgut) and primary tumor grading (G3), absence of concomitant LM, number (2-4), location (unilobar), grading (G3) of LM, and 25-50% hepatic involvement at the time of the metastatic disease diagnosis. Conclusions: Hepatic resection is nowadays the main treatment providing potential cure and prolonged survival, for patients with NEN when integrated in a multimodal strategy based on systemic therapy.

Ultrasound-Guided Liver Resection of a Tumor Involving the Hepatocaval Confluence.

We present the case of a 72-year-old patient with multiple cardiovascular comorbidities, hospitalized in our center for a liver tumor, impossible to biopsy percutaneously. CT examination detected a tumor formation with radiological features of cholangiocarcinoma, located in the upper part of segment I, extending to segments VII, VIII, IV superior and II, invading the right and middle hepatic vein, adherent to the left hepatic vein and to the retrohepatic inferior vena cava. Worth mentioning is the existence of 2 accessory lower right hepatic veins, which allowed us to perform a superior transverse non-anatomical ultrasound resection of the upper I, VII, VIII, IV and II segments, which also involved the right and middle hepatic veins, preserving the left hepatic vein, by detaching the tumor from it, but also from the retrohepatic inferior vena cava. Although the literature still debates the R1 vascular resection for cholangiocarcinoma, we decided to adopt this approach on the hepatic veins. Of note, we consider this policy not applicable for the portal pedicles. By adopting this strategy, the venous drainage of the remaining left hemiliver was ensured by the hepatic vein, and of the right one by the accessory veins. Although resecting tumors located at the hepato-caval confluence involving all hepatic veins is technically difficult, we consider it feasible especially when intraoperative ultrasound is used. (video article https://www.revistachirurgia.ro/pdfs/video/Ultrasound-Guided-Liver-Resection-Tumor-2282.mp4).

Resection of Giant Liver Metastasis of Gastrointestinal Stromal Tumor Using Intraoperative Ultrasound Guidance.

We present the case of a 37-year-old patient with a surgical history of a gastrointestinal stromal tumor with jejunal location, AFIP classification 6a, hospitalized in our center for synchronous liver metastases. The oncological assessment performed after 12 months from surgery for primary tumor, during which Imatinib was administered, reveals stable disease. CT scan showed a single very large centrally located liver metastasis, 14 cm in diameter, involving segments V and VIII IV, IV and VII, compressing the main portal bifurcation, right hepatic vein, umbilical (scizural) vein and left hepatic vein, invading the middle hepatic vein. We considered it feasible to apply the concept of R1 vascular resection, performing a limited, non-anatomical, ultrasound-guided central hepatectomy, allowing detachment of the tumor from the right hepatic vein and from the umbilical vein. Thus, we sacrificed only the ventral portal pedicles of segments V and VIII and partially preserved these segments to avoid the risk of post-resection liver failure.Currently, the patient is disease-free after 53 months, supporting the concept of ultrasound-guided R1 vascular resection, in the context of systemic therapy with tyrosine kinase inhibitors for metastases of stromal gastrointestinal tumors. (video article https://www.revistachirurgia.ro/pdfs/video/Liver-Resection-Metastases-Stromal-Tumors-2283.mp4).

En-Bloc Complete Segment 1 Resection and Left Hepatectomy for Klatskin Tumor.

video width="640" height="480" controls controlsList="nodownload" poster="https://www.revistachirurgia.ro/pdfs/video/Complete_segment_resection_hepatectomy_klatskin_tumor.jpg" style="margin-top: -20px;" source src="https://www.revistachirurgia.ro/pdfs/video/Complete_segment_resection_hepatectomy_klatskin_tumor.mp4" type="video/mp4" Your browser does not support the video tag. /video We present the case of a 37-year-old male patient with no significant history, hospitalized in our center for painless jaundice with sudden onset. CT contrast portal phase imaging revealed a tumor located at the main biliary confluence, in the proximity of the main portal bifurcation, with no venous or arterial vascular invasion, nor extrahepatic metastases. MRCP diagnosed a Bismuth- Corlette type Klatskin IIIb tumor. For complete assessment of biliary involvement and surgical planning, in addition to the Bismuth-Corlette classification, we took into consideration the presence of infiltration of the bile ducts for segment 1, documented at MRCP. Therefore, a left hepatectomy with en-bloc complete segment 1 resection, along with the main bile ducts and hilar lymphadenectomy, was considered best suited for achieving curative resection in this case. After an uneventful postoperative course, the patient was discharged in the 12th postoperative day. Currently, the patient is disease-free after 84 months. We consider that the long-term recurrence free survival was favored by the complete segment 1 resection. Therefore, for complete assessment of biliary involvement in Klatskin tumor, we recommend that in addition to Bismuth-Corlette classification, infiltration of the bile duct for segment 1 should always be evaluated. If present, the entire segment 1 should be removed for best oncological results.

Liver Resection for Metastases from Gastrointestinal Stromal Tumors: Does it Improve Long-Term Survival?

BACKGROUND AIMS: The emergence of tyrosine kinase inhibitors, radically altered the management of GISTs and sparked controversy regarding the role of hepatic resection for metastatic tumors. This study aims to identify whether there is improvement in the overall survival of patients with gastrointestinal liver metastases, undergoing hepatic resection in the context of multimodal treatment strategy, as to those approached only by systemic therapy. Methods: Using a retrospective database, we identified 57 patients treated at our center over a 12-year period: Group A (n=31) underwent hepatic resection alongside systemic therapies, and B (n=26) only systemic therapies. In order to obtain a more robust sample, needed for the survival analysis, we performed a propensity score matching and a bootstrapping selection with Jackknife correction for errors; thus, we created an extended sample of 1000 virtual patients. Results: The overall survival measured in all patients was 47 months (95%CI:34-60); significantly higher for group A (56 months, 95%CI:37-75) compared to group B (38 months, 95%CI:19-56), (p=0.007, Log Rank test). Multivariate analysis identified one risk factor: the presence synchronous liver metastases upon diagnosis of primary. Conclusions: Liver resection following TKI therapy is the current mainstay of treatment strategy for potential cure and prolonged survival, in appropriately selected patients evaluated in an multidisciplinary tumor board.

Definitive Surgery for Liver Trauma in a Tertiary HPB Center (with video).

Background: Surgery for severe liver trauma remains challenging even for HPB surgeons, mainly due the hemodynamical instability, involvement of major vascular and biliary elements, impaired background liver and frequent anatomical variants. In this setting, despite conservative policy, major liver resection is still required in selected cases. Also salvage liver transplantation may be needed. Our study aims to analyze the results after definitive surgery for hepatic injury (HI) in a tertiary HPB center. Methods: Sixty-six patients with HI were admitted and treated in our center between June 2000 and June 2021. The median age was 29 years (mean 35, range 10-76). The male/female ratio was 50/16. According to the American Association for the Surgery of Trauma (AAST) system, HIs were grade II in one patient (1.5%), grade III in 11 pts (16.7%), grade IV in 25 pts (37.9%), and grade V in 29 pts (43.9%); no patient had grade I or VI HI. Results: Fifty-two pts (78.8%) benefitted from surgery and 14 pts (21.2%) from non-operative treatment (NOT). Perihepatic packing was previously performed in 38 pts (73.1%). Surgery consisted in hepatic resections (HR) in 51 pts (77.3%) and liver transplantation in one patient (1.5%). The rate of major HR was 51.9% (27 HRs). The overall major morbidity and mortality rates were 33.3% (20 pts) and 13.6% (9 pts), respectively. For surgery, the major complication rate was 35.3% (18 pts), while for major and minor HR were 40.7% (11 pts) and 29.2% (7 pts), respectively; the mortality rate was 15.7% (8 pts). After NOT, the major morbidity and mortality rates were 14.3% (2 pts) and 7.1% (1 pt), respectively. Conclusions: Hepatic resections, especially major ones and/or involving vascular and biliary reconstructions, as well as non-operative treatment for severe hepatic injuries, are to be carried out in tertiary HPB centers, thus minimizing the morbidity and mortality rates, while having the liver transplantation as salvage option.

Hypothermic Oxygenated Machine Perfusion of Liver Grafts: Preliminary Experience in a Single Center.

Background: The need to maximize the use of donor organs and the issue of ischemia-reperfusion injury led to the use of thermoregulated oxygenated machine perfusion that improves the function of liver graft prior to transplantation. Among these methods, the HOPE (hypothermic oxygenated perfusion) protocol shows significant benefits. The aim of the paper is to analyze the early experience in using such procedure in a high-volume liver transplantation center. Methods: Normal liver grafts with cold ischemia time â?¥6 hours, marginal grafts and discarded (beyond ECD criteria) grafts were perfused using HOPE. Our selection criteria for dual HOPE (hepatic artery and portal perfusion) were steatosis, at least 3 associated ECD criteria, and discarded grafts. The main criteria to establish graft improvement were the progressive increase of arterial and portal flows, with lactate under 3 mmol/L or, even if over this value, with a decreasing trend during perfusion. Results: Whole liver grafts harvested from 28 donors between February 2016 and June 2021 benefitted from HOPE: 9 otherwise discarded grafts were assessed and considered not fit for transplantation, while the other 19 were ECD or standard grafts that were subsequently transplanted. Dual HOPE was used in 8 out of the 19 procedures (42.1%). We obtained a significant increase of arterial and portal flow (p=0.005 and p=0.001, respectively). In recipients, significant improvement of AST, ALT, INR and lactate values were recorded (p 0.001, p 0.001, p 0.001, and p=0.05, respectively). The rate of major postoperative complications (Dindo-Clavien grade 3) after LT was 26.3%, while the rate of early graft dysfunction was 15.8%. No PRS or acute rejection was recorded. The postoperative mortality rate was 15.8%. After a median follow-up of 9.3 months (range 2-44), the late major complication rate was 15.8%, without mortality. Conclusion: Machine perfusion is nowadays part of current clinical practice. This way, marginal liver grafts (DCD, ECD-DBD) may be safely used for transplantation improving the outcome, thus effectively enhance the use of a persistent scarce pool of donors. For best results, we believe that both techniques of HOPE (mono and dual HOPE) should be used based on specific selection criteria.

Continuous Noninvasive Hemoglobin Monitoring Reflects the Development of Acute Hemodilution After Consecutive Fluid Challenges.

BACKGROUND: Consecutive fluid challenges (FCs) are frequently administered to maximize the stroke volume (SV) as part of a goal-directed therapy (GDT) strategy. However, fluid administration may also cause acute hemodilution that might lead to an actual paradoxical decrease in oxygen delivery (DO2). The aim of this study was to examine whether continuous noninvasive hemoglobin (SpHb) monitoring can be used to detect the development of acute hemodilution after graded fluid administration. METHODS: In 40 patients who underwent major vascular or gastrointestinal surgery, an FC, consisting of 250 mL colloid solution, was administered. When the SV increased by ≥10%, the FC was repeated up to a maximum of 3 times. Laboratory-measured hemoglobin concentrations (BHb), SpHb, SV, cardiac output (CO), and DO2 values were recorded after each FC. RESULTS: All 40 patients received the first FC, 32 patients received the second FC, and 20 patients received the third FC (total of 750 mL). Out of the 92 administered FCs, only 55 (60%) caused an increase in SV ≥10% ("responders"). The first and the second FCs were associated with a significant increase in the mean CO and DO2, while the mean SpHb and BHb decreased significantly. However, the third and last FC was associated with no statistical difference in CO and SV, a further significant decrease in mean SpHb and BHb, and a significant decrease in DO2 in these patients. Compared to their baseline values (T0), BHb and SpHb decreased by a mean of 5.3% ± 4.9% and 4.4% ± 5.2%, respectively, after the first FC (T1; n = 40), by 9.7% ± 8.4% and 7.9% ± 6.9% after the second FC (T2; n = 32), and by 14.5% ± 6.2% and 14.6% ± 5.7% after the third FC (T3; n = 20). Concordance rates between the changes in SpHb and in BHb after the administration of 250, 500, and 750 mL colloids were 83%, 90%, and 100%, respectively. CONCLUSIONS: Fluid loading aimed at increasing the SV and the DO2 as part of GDT strategy is associated with acute significant decreases in both BHb and SpHb concentrations. When the administration of an FC is not followed by a significant increase (≥10%) in the SV, the DO2 decreases significantly due to the development of acute hemodilution. Continuous noninvasive monitoring of SpHb does not reflect accurately absolute BHb values, but may be reliably used to detect the development of acute hemodilution especially after the administration of at least 500 mL of colloids.

Obesity is associated with decreased lung compliance and hypercapnia during robotic assisted surgery.

Robotic assisted surgery (RAS) represents a great challenge for anesthesiology due to the increased intraabdomial pressures required for surgical optimal approach. The changes in lung physiology are difficult to predict and require fast decision making in order to prevent altered gas exchange. The aim of this study was to document the combined effect of patient physical status, medical history and intraoperative position during RAS on lung physiology and to determine perioperative risk factors for hypercapnia. We prospectively analyzed 62 patients who underwent elective RAS. Age, co-morbidities and body mass index (BMI) were recorded before surgery. Ventilatory parameters and arterial blood gas analysis were determined before induction of anesthesia, after tracheal intubation and on an hourly basis until the end of surgery. In RAS, the induction of pneumoperitoneum was associated with a significant decrease in lung compliance from a mean of 42.5-26.7 ml cm H2O-1 (p = 0.001) and an increase in plateau pressure from a mean of 16.1 mmHg to a mean of 23.6 mmHg (p = 0.001). Obesity, demonstrated by a BMI over 30, significantly correlates with a decrease in lung compliance after induction of anesthesia (p = 0.001). A significant higher increase in arterial CO2 tension was registered in patients undergoing RAS in steep Trendelenburg position (p = 0.05), but no significant changes in end-tidal CO2 were recorded. A higher arterial to end-tidal CO2 tension gradient was observed in patients with a BMI > 30 (p < 0.001). In conclusion, patients' physical status, especially obesity, represents the main risk factor for decreased lung compliance during RAS and patient positioning in either Trendelenburg or steep Trendelenburg during surgery has limited effects on respiratory physiology.

Resection of Concomitant Hepatic and Extrahepatic Metastases from Colorectal Cancer - A Worthwhile Operation?

Background: The benefit of hepatic resection in case of concomitant colorectal hepatic and extrahepatic metastases (CHEHMs) is still debatable. The purpose of this study is to assess the results of resection of hepatic and extrahepatic metastases in patients with CHEHMs in a high-volume center for both hepatobiliary and colorectal surgery and to identify prognostic factors that correlate with longer survival in these patients. METHOD: It was performed a retrospective analysis of 678 consecutive patients with liver resection for colorectal cancer metastases operated in a single Centre between April 1996 and March 2016. Among these, 73 patients presented CHEHMs. Univariate analysis was performed to identify the risk factors for overall survival (OS) in these patients. Results: There were 20 CHMs located at the lymphatic node level, 20 at the peritoneal level, 12 at the ovary and lung level, 12 presenting as local relapses and 9 other sites. 53 curative resections (R0) were performed. The difference in overall survival between the CHEHMs group and the CHMs group is statistically significant for the entire groups (p 0.0001), as well as in patients who underwent R0 resection (p 0.0001). In CHEHMs group, the OS was statistically significant higher in patients who underwent R0 resection vs. those with R1/R2 resection (p=0.004). Three variables were identified as prognostic factors for poor OS following univariate analysis: 4 or more hepatic metastases, major hepatectomy and the performance of operation during first period of the study (1996 - 2004). There was a tendency toward better OS in patients with ovarian or pulmonary location of extrahepatic disease, although the difference was not statistically significant. CONCLUSION: In patients with concomitant hepatic and extrahepatic metastases, complete resection of metastatic burden significantly prolong survival. The patients with up to 4 liver metastases, resectable by minor hepatectomy benefit the most from this aggressive onco-surgical management.