Platelets are tightly connected with the liver, as both their production and their clearance are mediated by the liver. Platelets, in return, participate in a variety of liver diseases, ranging from ...non-alcoholic fatty liver diseases, (viral) hepatitis, liver fibrosis and hepatocellular carcinoma to liver regeneration. Due to their versatile functions, which include (1) regulation of hemostasis, (2) fine-tuning of immune responses and (3) release of growth factors and cellular mediators, platelets quickly adapt to environmental changes and modulate disease development, leading to different layers of complexity. Depending on the (patho)physiological context, platelets exert both beneficial and detrimental functions. Understanding the precise mechanisms through which platelet function is regulated at different stages of liver diseases and how platelets interact with various resident and non-resident liver cells helps to draw a clear picture of platelet-related therapeutic interventions. Therefore, this review summarizes the current knowledge on platelets in acute and chronic liver diseases and aims to shed light on how the smallest cells in the circulatory system account for changes in the (patho)physiology of the second largest organ in the human body.
The death of laparoscopy Ferrari, Davide; Violante, Tommaso; Novelli, Marco ...
Surgical endoscopy,
05/2024, Letnik:
38, Številka:
5
Journal Article
Recenzirano
Background
The introduction of laparoscopy in 1989 revolutionized surgical practices, reducing post-operative complications, and enhancing outcomes. Despite its benefits, limitations in laparoscopic ...tools have led to continued use of open surgery. Robotic-assisted surgery emerged to address these limitations, but its adoption trends and potential impact on open and laparoscopic surgery require analysis.
Methods
A retrospective analysis used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) databases from 2012 to 2021. The study encompassed various abdominal procedures, employing Vector Autoregressive (VAR) models to analyze the dynamic relationships between surgical techniques. The models predicted future trends in open, laparoscopic, and robotic surgery until Q2 of 2025.
Results
The analysis included 360,171 patients across diverse procedures. In urology, robotic surgery dominated prostatectomies (83.1% in 2021) and nephrectomies (55.1% in 2021), while the open approach remained the predominant surgical technique for cystectomies (72.5% in 2021). In general surgery, robotic colectomies were forecasted to surpass laparoscopy, becoming the primary approach by 2024 (45.7% in 2025). Proctectomies also showed a shift towards robotic surgery, predicted to surpass laparoscopy and open surgery by 2025 (32.3%). Pancreatectomies witnessed a steady growth in robotic surgery, surpassing laparoscopy in 2021, with forecasts indicating further increase. While hepatectomies remained predominantly open (70.0% in 2025), esophagectomies saw a rise in robotic surgery, predicted to become the primary approach by 2025 (52.3%).
Conclusions
The study suggests a transformative shift towards robotic-assisted surgery, poised to dominate various minimally invasive procedures. The forecasts indicate that robotic surgery may surpass laparoscopy and open surgery in colectomies, proctectomies, pancreatectomies, and esophagectomies by 2025. This anticipated change emphasizes the need for proactive adjustments in surgical training programs to align with evolving surgical practices. The findings have substantial implications for future healthcare practices, necessitating a balance between traditional laparoscopy and the burgeoning role of robotic-assisted surgery.
Platelets play a pivotal role in stimulating liver regeneration after partial hepatectomy in rodents and humans. Liver regeneration in rodents is delayed when platelets are inhibited. However, the ...exact mechanisms whereby platelets accumulate and promote liver regeneration remain uncertain. Thrombin-dependent intrahepatic fibrin(ogen) deposition was recently reported after partial hepatectomy (PHx) in mice, but the role of fibrin(ogen) deposits in liver regeneration has not been investigated. We tested the hypothesis that fibrin(ogen) contributes to liver regeneration by promoting intrahepatic platelet accumulation and identified the trigger of rapid intrahepatic coagulation after PHx. PHx in wild-type mice triggered rapid intrahepatic coagulation, evidenced by intrahepatic fibrin(ogen) deposition. Intrahepatic fibrin(ogen) deposition was abolished in mice with liver-specific tissue factor deficiency, pinpointing the trigger of coagulation after PHx. Direct thrombin activation of platelets through protease-activated receptor-4 did not contribute to hepatocyte proliferation after PHx, indicating that thrombin contributes to liver regeneration primarily by driving intrahepatic fibrin(ogen) deposition. Fibrinogen depletion with ancrod reduced both intrahepatic platelet accumulation and hepatocyte proliferation after PHx, indicating that fibrin(ogen) contributes to liver regeneration after PHx by promoting intrahepatic platelet accumulation. Consistent with the protective function of fibrin(ogen) in mice, low postoperative plasma fibrinogen levels were associated with liver dysfunction and mortality in patients undergoing liver resection. Moreover, increased intrahepatic fibrin(ogen) deposition was evident in livers of patients after liver resection but was remarkably absent in patients displaying hepatic dysfunction postresection. The results suggest a novel mechanism whereby coagulation-dependent intrahepatic fibrin(ogen) deposition drives platelet accumulation and liver regeneration after PHx.
•Liver-associated tissue factor drives rapid intrahepatic coagulation after PHx.•Intrahepatic fibrin(ogen) deposition, but not thrombin-mediated platelet activation, promotes liver regeneration after PHx.
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Platelets store a plethora of different molecules within their granules, modulating numerous pathways, not only in coagulation, but also in angiogenesis, wound healing, and inflammatory diseases. ...These molecules get rapidly released upon activation and therefore represent an easily accessible indirect marker for platelet activation. Accurate analysis of platelet-derived molecules in the plasma requires appropriate anticoagulation to avoid in vitro activation and subsequent degranulation of platelets, potentially causing artificially high levels and masking biologically relevant differences within translational research studies. However, there is still enormous heterogeneity among anticoagulants used to prevent unwanted platelet activation, so that plasma levels reported for platelet granule contents range over several orders of magnitude. To address this problem and to define the most robust method of plasma preparation to avoid in vitro platelet activation during processing, we compared plasma concentrations of the three platelet-stored factors thrombospondin (TSP-1), platelet factor 4 (PF4), and soluble P-selectin (sCD62P) between human blood samples anticoagulated with either citrate-theophylline-adenosine-dipyridamole (CTAD), acid-citrate-dextrose (ACD), citrate, ethylenediaminetetraacetic acid (EDTA) or heparin. Additionally, we assessed the effect of storage temperature and time between blood drawing and sample processing within the differentially anticoagulated samples. Our data strongly support the use of CTAD as anticoagulant for determining plasma concentrations of platelet-stored molecules, as anticoagulation with heparin or EDTA led to a 12.4- or 8.3-fold increase in plasma levels of PF4, respectively. Whereas ACD was similar effective as CTAD, citrate only showed comparable PF4 plasma levels when plasma was kept at 4°C. Moreover, blood sampling with CTAD as anticoagulant resulted in the most reproducible values, even when samples were processed at ambient temperature or after storage over 6 hours. In the latter case, anticoagulation with heparin or EDTA led to artificially high plasma levels indicative of in vitro platelet activation. Therefore, we want to raise scientific awareness for choosing CTAD as optimal anticoagulant for the detection of platelet-stored molecules in plasma.
Postoperative liver dysfunction may lead to morbidity and mortality after liver resection. Preoperative liver function assessment is critical to identify preexisting liver dysfunction in patients ...prior to resection. The aim of this study was to evaluate the predictive potential of perioperative indocyanine green (ICG)-clearance testing to prevent postoperative liver dysfunction and morbidity using standardized outcome parameters in a routine Western-clinical-setting.
137 patients undergoing partial hepatectomy between 2011 and 2013, at the general hospital of Vienna, were included. ICG-clearance was recorded one day prior to surgery as well as on the first and fifth postoperative day. Postoperative liver dysfunction was defined according to the International Study Group of Liver Surgery and evaluation of morbidity was based on the Dindo-Clavien classification. Statistical analyses were based on non-parametric tests.
Preoperative reduced ICG-plasma disappearance rate (PDR) as well as increased ICG-retention rate at 15 min (R15) were able to significantly predict postoperative liver dysfunction (Area under the curve = PDR: 0.716, P = 0.018; R15: 0.719, P = 0.016). Furthermore, PDR <17%/min. or R15 >8%, were able to accurately predict postoperative complications prior to surgery. In addition to this, ICG-clearance on postoperative day 1 comparably predicted postoperative liver dysfunction (Area under the curve = PDR: 0.895; R15: 0.893; both P <0.001), specifically, PDR <10%/min or R15 >20% on postoperative day 1 predicted poor postoperative outcome.
PDR and R15 may represent useful parameters to distinguish preoperative high and low risk patients in a Western collective as well as on postoperative day 1, to identify patients who require closer monitoring for potential complications.
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•Preoperative IP5-HT levels affect patient outcomes after liver resection for liver tumors.•There is a narrow window of IP5-HT levels where liver regeneration and tumor progression is ...balanced.•High IP5-HT levels (>134ng/ml IP5-HT) lead to an increased incidence of early tumor recurrence.•Low IP5-HT levels (<73ng/ml IP5-HT) lead to a higher rate of morbidity.
Besides its critical role during liver regeneration, serotonin (5-HT) has been found to act as a mitogenic factor in several neoplastic entities. Accordingly, we aimed to evaluate whether intra-platelet 5-HT (IP5-HT) was associated with oncological outcome after liver resection and concomitantly evaluate its ability to serve as a therapeutic target to promote liver regeneration.
A total of 96 patients undergoing liver resection for malignant liver tumors were prospectively included. Optimized plasma and serum preparation were performed and IP5-HT levels were determined. Patients were followed up for postoperative liver dysfunction (LD), morbidity, disease free and overall survival (OS).
We found increased preoperative IP5-HT levels in patients with disease recurrence at 6 and 12months (p=0.046, p=0.020, respectively). In clear contrast, patients suffering from postoperative morbidity, severe morbidity or LD had significantly reduced IP5-HT levels (p=0.011, p=0.035, p=0.003, respectively). Patients with high IP5-HT levels (>134ng/ml) suffered from an increased incidence of postoperative disease recurrence at 6 and 12months (p=0.045, p=0.006, respectively) but exhibited a reduction in morbidity, severe morbidity, and LD (p=0.006, p=0.008, p=0.005, respectively). We confirmed these results in our two largest subgroups, demonstrating that they were independent of tumor type. This bivalent effect of IP5-HT was also reflected in patients receiving selective serotonin reuptake inhibitor treatment, who displayed a reduction in disease recurrence accompanied by an increase in postoperative morbidity. Yet, both early disease recurrence and morbidity worsened OS.
Herein, we present first clinical evidence for IP5-HT being associated with early disease recurrence after liver resection in humans. Thus, pharmacological intervention at the level of platelets and platelet-derived 5-HT to promote liver regeneration should be considered with caution. A careful definition of indications and timing is needed to promote liver regeneration without inducing deleterious effects.
Preoperative intra-platelet serotonin (IP5-HT) levels seem to substantially affect patient outcomes after liver resection for liver tumors. While there is a narrow window of IP5-HT levels where liver regeneration and tumor progression is balanced, excessively high IP5-HT levels (>134ng/ml IP5-HT) lead to an increased incidence of early tumor recurrence and excessively low IP5-HT levels (<73ng/ml IP5-HT) lead to a higher rate of morbidity. Ultimately, overall survival is negatively affected by both postoperative early disease recurrence and morbidity.
ClinicalTrials.gov-Identifier: NCT01700231.
Background
The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to ...have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy.
Methods
All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS).
Results
This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (
p
= 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%;
p
= 0.447), CA19.9 normalization (85% vs. 76%,
p
= 0.290), and radiological response (32% vs. 37%,
p
= 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan–Meier analysis, with a
p
-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death.
Conclusions
I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.
Portal or superior mesenteric vein (PV-SMV) resection and reconstruction is sometimes required during pancreatic tumor resection. In patients requiring segmental venous resection with interposition ...grafting, the left renal vein (LRV) is an accessible autologous solution. However, long-term patency outcomes of the LRV as an interposition conduit in this setting have not been analyzed.
We conducted a retrospective analysis of patients undergoing pancreatic resection with PV-SMV reconstruction using LRV between 2002 and 2022. The primary outcome was PV-SMV patency at last follow-up, assessed with postoperative CT scans and analyzed using Kaplan-Meier survival methods that account for variation in follow-up duration. Development of any postoperative acute kidney injury within 7 days of surgery and morbidity were secondary outcomes.
The study cohort includes 65 patients who underwent LRV harvest; 60 (92%) ultimately underwent successful reconstruction with harvested LRV graft. Kaplan-Meier 2-year estimated patency rate of the LRV graft was 88%, with no cases of complete occlusion. Six (10%) patients experienced graft stenosis. Nine of 61 (15%) patients experienced grade II or III acute kidney injury, 6 of 9 returning to normal renal function before discharge. No difference in median serum creatinine was observed at baseline, 6 and 12 months from surgery. LRV remnant thrombosis was seen in 7 of 65 (11%) patients. Only 3 of 61 (5%) patients had persistent acute kidney injury caused by complications unrelated to LRV harvesting.
Autologous LRV graft was a reliable conduit for segmental PV-SMV reconstruction, resulting in a high patency rate and marginal impact on renal function. LRV harvest is a safe and potentially ideal surgical option for PV-SMV reconstruction in pancreatic surgery.
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