71 research outputs found
Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) A Stepwise Evaluation of a New Surgical Procedure
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Constitutive androstane receptor (Car)-driven regeneration protects liver from failure following tissue loss
No full textBackground & Aims Liver can recover following resection. If tissue loss is too excessive, however, liver failure will develop as is known from the small-for-size-syndrome (SFSS). The molecular processes underlying liver failure are ill-understood. Here, we explored the role and the clinical potential of Nr1i3 (constitutive androstane receptor, Car) in liver failure following hepatectomy. Methods Activators of Car, various hepatectomies, Car-/- mice, humanized CAR mice, human tissue and ex vivo liver slice cultures were used to study Car in the SFSS. Pathways downstream of Car were investigated by in vivo siRNA knockdown. Results Excessive tissue loss causing liver failure is associated with deficient induction of Car. Reactivation of Car by an agonist normalizes all features associated with experimental SFSS. The beneficial effects of Car activation are relayed through Foxm1, an essential promoter of the hepatocyte cell cycle. Deficiency in the CAR-FOXM1 axis likewise is evident in human SFSS. Activation of human CAR mitigates SFSS in humanized CAR mice and improves the culture of human liver slices. Conclusions Impaired hepatic Car-Foxm1 signaling provides a first molecular characterization of liver that fails to recover after tissue loss. Our findings place deficient regeneration as a principal cause behind the SFSS and suggest CAR agonists may bear clinical potential against liver failure. Lay summary The unique regenerative capacity of liver has its natural limits. Following tissue loss that is too excessive, such as through extended resection in the clinic, liver failure may develop. This is known as small-for-size-syndrome (SFSS) and represents the most frequent cause of death due to liver surgery. Here we show that deficient induction of the protein Car, a central regulator of liver function and growth, is a cause of liver failure following extended resection; reactivation of Car through pharmacological means is sufficient to prevent or rescue the SFS
Reply to the Letter: Improving the Safety of ALPPS Procedure: The Optimal Compromise Between the Optimal Compromise Between Drop-out and Mortality Risk? Comment on: Schadde E et al Prediction of Mortality After ALPPS Stage-1: An Analysis of 320 Patients From the International ALPPS Registry. Ann Surg. 2015;262: 780-786.
Get PDFParenchyma-Sparing Liver Resection or Regenerative Liver Surgery: Which Way to Go?
No full textLiver resection for malignant tumors should respect oncological margins while ensuring safety and improving the quality of life, therefore tumor staging, underlying liver disease and performance status should all be attentively assessed in the decision process. The concept of parenchyma-sparing liver surgery is nowadays used as an alternative to major hepatectomies to address deeply located lesions with intricate topography by means of complex multiplanar parenchyma-sparing liver resections, preferably under the guidance of intraoperative ultrasound. Regenerative liver surgery evolved as a liver growth induction method to increase resectability by stimulating the hypertrophy of the parenchyma intended to remain after resection (referred to as future liver remnant), achievable by portal vein embolization and liver venous deprivation as interventional approaches, and portal vein ligation and associating liver partition and portal vein ligation for staged hepatectomy as surgical techniques. Interestingly, although both strategies have the same conceptual origin, they eventually became caught in the never-ending parenchyma-sparing liver surgery vs. regenerative liver surgery debate. However, these strategies are both valid and must both be mastered and used to increase resectability. In our opinion, we consider parenchyma-sparing liver surgery along with techniques of complex liver resection and intraoperative ultrasound guidance the preferred strategy to treat liver tumors. In addition, liver volume-manipulating regenerative surgery should be employed when resectability needs to be extended beyond the possibilities of parenchyma-sparing liver surgery
Timing of surgical repair of bile duct injuries after laparoscopic cholecystectomy: A systematic review
No full textBackground: The surgical management of bile duct injuries (BDIs) after laparoscopic cholecystectomy (LC) is challenging and the optimal timing of surgery remains unclear. The primary aim of this study was to systematically evaluate the evidence behind the timing of BDI repair after LC in the literature. Aim: To assess timing of surgical repair of BDI and postoperative complications. Methods: The MEDLINE, EMBASE, and The Cochrane Library databases were systematically screened up to August 2021. Risk of bias was assessed via the Newcastle Ottawa scale. The primary outcomes of this review included the timing of BDI repair and postoperative complications. Results: A total of 439 abstracts were screened, and 24 studies were included with 15609 patients included in this review. Of the 5229 BDIs reported, 4934 (94%) were classified as major injury. Timing of bile duct repair was immediate (14%, n = 705), early (28%, n = 1367), delayed (28%, n = 1367), or late (26%, n = 1286). Standardization of definition for timing of repair was remarkably poor among studies. Definitions for immediate repair ranged from < 24 h to 6 wk after LC while early repair ranged from < 24 h to 12 wk. Likewise, delayed (> 24 h to > 12 wk after LC) and late repair (> 6 wk after LC) showed a broad overlap. Conclusion: The lack of standardization among studies precludes any conclusive recommendation on optimal timing of BDI repair after LC. This finding indicates an urgent need for a standardized reporting system of BDI repair
Ablation Strategies for Locally Advanced Pancreatic Cancer
Get PDFWith the advent of novel and somewhat effective chemotherapy against pancreas cancer, several groups developed a new interest on locally advanced pancreatic cancer (LAPC). Unresectable tumors constitute up to 80% of pancreatic cancer (PC) at the time of diagnosis and are associated with a 5-year overall survival of less than 5%. To control those tumors locally, with perhaps improved patients survival, significant advances were made over the last 2 decades in the development of ablation methods including cryoablation, radiofrequency ablation, microwave ablation, high intensity focused ultrasound and irreversible electroporation (IRE). Many suggested a call for caution for possible severe or lethal complications in using such techniques on the pancreas. Most fears were on the heating or freezing of the pancreas, while non-thermal ablation (IRE) could offer safer approaches. The multimodal therapies along with high-resolution imaging guidance have created some enthusiasm toward ablation for LAPC. The impact of ablation techniques on primarily non-resectable PC remains, however, unclear
Omega-3 fatty acids protect fatty and lean mouse livers after major hepatectomy
Get PDFObjective: To evaluate the regional distribution of ventilation in horses during spontaneous breathing and controlled mechanical ventilation (CMV) using electrical impedance tomography (EIT).
Study design: Prospective, experimental case series.
Animals: Four anaesthetized experimental horses.
Methods: Horses were anaesthetized with isoflurane in an oxygen-air mixture and medetomidine continuous rate infusion, placed in dorsal recumbency with an EIT belt around the thorax, and allowed to breathe spontaneously until PaCO2 reached 13.3 kPa (100 mmHg), when volume CMV was started. For each horse, the EIT signal was recorded for at least 2 minutes immediately before (T1), and at 30 (n = 3) or 60 (n = 1) minutes after the start of CMV (T2). The centre of ventilation (CoV), dependent silent spaces (DSS) (likely to represent atelectatic lung areas), non-dependent silent spaces (NSS) (likely to represent lung areas with low ventilation) and total ventilated area (TVA) were evaluated. Cardiac output (CO) was measured and venous admixture and oxygen delivery (DO2) were calculated at T1 and T2. Data are presented as median and range.
Results: After the initiation of CMV, the CoV moved ventrally towards the non-dependent lung by 10% [from 57.4% (49.6–60.2%) to 48.3% (41.9–54.4%)]. DSS increased [from 4.1% (0.2–13.9%) to 18.7% (7.5–27.5%)], while NSS [21.7% (9.4–29.2%) to 9.9% (1.0–20.7%)] and TVA [920 (699–1051) to 837 (662–961) pixels] decreased. CO, venous admixture and DO2 also decreased.
Conclusions and clinical relevance: In spontaneously breathing anaesthetized horses in dorsal recumbency, ventilation was essentially centred within the dependent dorsal lung regions and moved towards non-dependent ventral regions as soon as CMV was started. This shows a major lack of ventilation in the dependent lung, which may be indicative of atelectasis
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