Abstract
Background
The risk of death after surgery for perihilar cholangiocarcinoma is high; nearly one in every five patients dies within 90 days after surgery. When the oncological benefit is ...limited, a high-risk resection may not be justified. This retrospective cohort study aimed to create two preoperative prognostic models to predict 90-day mortality and overall survival (OS) after major liver resection for perihilar cholangiocarcinoma.
Methods
Separate models were built with factors known before surgery using multivariable regression analysis for 90-day mortality and OS. Patients were categorized in three groups: favourable profile for surgical resection (90-day mortality rate below 10 per cent and predicted OS more than 3 years), unfavourable profile (90-day mortality rate above 25 per cent and/or predicted OS below 1.5 years), and an intermediate group.
Results
A total of 1673 patients were included. Independent risk factors for both 90-day mortality and OS included ASA grade III–IV, large tumour diameter, and right-sided hepatectomy. Additional risk factors for 90-day mortality were advanced age and preoperative cholangitis; those for long-term OS were high BMI, preoperative jaundice, Bismuth IV, and hepatic artery involvement. In total, 294 patients (17.6 per cent) had a favourable risk profile for surgery (90-day mortality rate 5.8 per cent and median OS 42 months), 271 patients (16.2 per cent) an unfavourable risk profile (90-day mortality rate 26.8 per cent and median OS 16 months), and 1108 patients (66.2 per cent) an intermediate risk profile (90-day mortality rate 12.5 per cent and median OS 27 months).
Conclusion
Preoperative risk models for 90-day mortality and OS can help identify patients with resectable perihilar cholangiocarcinoma who are unlikely to benefit from surgical resection. Tailored shared decision-making is particularly essential for the large intermediate group.
When the oncological benefit is limited, a high-risk resection may be not be justified. Two preoperative prognostic models were created to predict 90-day mortality and survival after major liver resection for perihilar cholangiocarcinoma. These can help identify patients with resectable perihilar cholangiocarcinoma who are unlikely to benefit from surgical resection.
An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI ...cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA), two-second messengers with versatile cellular functions. Notably, some DGK isoforms, such as DGKα, have been reported to possess promising therapeutic potential in cancer therapy. However, further studies are needed in order to better comprehend their involvement in cancer. In this review, we highlight that DGKs are an essential component of the PI cycle that localize within several subcellular compartments, including the nucleus and plasma membrane, together with their PI substrates and that they are involved in mediating major cancer cell mechanisms such as growth and metastasis. DGKs control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some DGKs control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA.
Aim
Textbook outcome (TO) is a new surgical quality measure that combines structure, process and surgical outcomes into a single element. Our study aimed to determine the incidence of TO after ...simultaneous rectal and liver surgery and to use the achievement of TO as a tool to identify the best candidates for these complex procedures.
Methods
In total, 256 patients who underwent simultaneous liver and rectal surgery for Stage IV rectal cancer between January 2004 and August 2019 at five tertiary centres were enrolled. TO was defined as a lack of complication, prolonged length of stay, readmission and death.
Results
Mortality rate at 90 days and major morbidity rate were 2.3% and 15.6%, respectively. An overall TO was achieved in 59% of the patients, which is associated with significantly improved overall (median TO 86.3 months vs. no TO 37.4 months) and disease‐free (median TO 70.6 months vs. no TO 24.9 months) survival. On multivariate analysis the presence of multi‐comorbidities (OR 3.073) was associated with a reduced likelihood of achieving TO. Left lateral sectionectomy/limited resection was a protective factor (OR 0.416).
Conclusion
TO was achieved in six of 10 patients undergoing simultaneous resections for rectal cancer and liver metastases. Achieving a TO is strongly associated with improved long‐term survival. The best candidates for these procedures were patients without multiple comorbidities and those treated with left lateral sectionectomy/limited resection.
Complete resection of perihilar cholangiocarcinoma (pCCA) is the only potentially curative treatment. Long-term survival data is rare and prognostic analyses are hindered by the rarity of the ...disease. This study aimed to determine the cure rate and to identify clinicopathological factors that may preclude cure. All consecutive resections for pathologically confirmed pCCA between 2000 and 2009 in 22 centers worldwide were included in a retrospective cohort study. Each center included its retrospective data series. A total of 460 patients were included with a median follow-up of 10 years for patients alive at last follow-up. Median overall survival (OS) was 29.9 months and 10-year OS was 12.8%. Twenty-nine (6%) patients reached 10-year OS. The observed cure rate was 5%. Factors that virtually precluded cure (i.e., below 1%) according to the mixture cure model included age above 70, Bismuth-Corlette type IV tumors, hepatic artery reconstruction, and positive resection margins. Cure was unlikely (i.e., below 3%) in patients with positive lymph nodes or poor tumor differentiation. These factors need to be considered in patient counseling and long-term follow-up after surgery.
Background
Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection.
Objective
...This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort.
Methods
Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection.
Results
A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (
p
< 0.001 and
p
= 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%,
p
< 0.001), as was biliary leakage (10% vs. 35%,
p
< 0.01), intra-abdominal abscesses (19% vs. 34%,
p
= 0.01), and 90-day mortality (7% vs. 18%,
p
= 0.03).
Conclusion
PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC.
In the present study, an organic substrate (coffee silverskin) enriched with spirulina (
; 15%
/
), as a source of lipids and bioactive molecules, was used to rear the black soldier fly (
) prepupae. ...Three grossly isonitrogenous, isoproteic, isolipidic and isoenergetic experimental diets for rainbow trout (
) juveniles were then produced: a control diet (HM0) mostly including fish meal and fish oil, and two other test diets named HM3 and HM20, in which 3 or 20% of the marine ingredients were substituted with full fat black soldier fly prepupae meal (HM), respectively. Experimental diets were provided for 6 weeks, and at the end of the trial the physiological responses and marketable traits of the fish were investigated using a multidisciplinary approach. Generally, all test diets were well accepted, and fish growth, gut and liver health status, and marketable characteristics were not impaired by the experimental diets. However, an increased immuno-related gene expression along with a slight reduction of fillet redness and yellowness was evident in fish from the HM20 group.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Aim
The identification of new prognostic factors able to stratify hepatocellular carcinoma patients candidate to first‐line therapy is urgent. In the present work we validated the prognostic value of ...the lenvatinib prognostic index.
Methods
Data of Eastern and Western patients treated with lenvatinib as first‐line for Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma were recollected. The lenvatinib prognostic index was composed by three classes of risk according with our previous study. The “low risk” group includes patients with prognostic nutritional index (PNI) >43.3 and with previous transarterial chemoembolization. The “medium risk” group includes patients with PNI >43.3, but without previous transarterial chemoembolization and patients with PNI <43.3, albumin‐bilirubin grade 1 and Barcelona Clinic Liver Cancer stage B. The “high risk” group includes patients with PNI <43.3, albumin‐bilirubin grade 2, and patients with PNI <43.3, albumin‐bilirubin grade 1 and Barcelona Clinic Liver Cancer stage C.
Results
A total of 717 patients were included. The median overall survival was 20.7 months (95% CI 16.1–51.6) in patients with low risk (n = 223), 16.7 months (95% CI 13.3–47.0) in patients with medium risk (n = 264), and 10.7 months (95% CI 9.3–12.2) in patients with high risk (n = 230; HR 1, 1.29, and 1.92, respectively; p < 0.0001). Median progression‐free survival was 7.3 months (95% CI 6.3–46.5) in patients with low risk, 6.4 months (95% CI 5.3–8.0) in patients with medium risk ,and 4.9 months (95% CI 4.3–5.5) in patients with high risk (HR 1, 1.07, 1.47 respectively; p = 0.0009).
Conclusion
The lenvatinib prognostic index confirms its prognostic value on an external cohort of hepatocellular carcinoma patients treated with Lenvatinib.
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•Strains L1 and L8 showed antagonistic activity against fruit postharvest pathogens.•SCAR 3f and SCAR 3r discriminated L1 and L8 among an A. pullulans population.•ddPCR determine the ...absolute cells number related to L1 and L8 DNA concentrations.
L1 and L8 are Aureobasidium pullulans strains previously shown to effectively act as biocontrol agents (BCA) against fruit postharvest pathogens. Here, L1 and L8 strains were tested in vivo against Monilinia laxa of peaches showing the ability to reduce the brown rot incidence by 95% and by 80% respectively. To develop future bioformulation and allow commercial use of these biocontrol agents (BCAs) it is necessary to develop specific identification tools. Since A. pullulans strains share very similar morphological features and are not distinguishable by visual analysis, the RAPD (Random Amplified Polymorphic DNA) technique was applied to genomic DNA of L1 and L8 and of other 40 different A. pullulans strains, and SCAR markers were developed from a L1 and L8 specific RAPD fragment of 984 bp. These primers amplify a fragment of 137 bp exclusively in L1 and L8, and can be used to distinguish the two yeasts strains from other A. pullulans strains with high specificity. The droplet digital PCR, used to determine the precise limit of detection (LOD), showed that these markers allow to detect up to 43 and 215 cells of L1 and L8 respectively.
Background
The TOPAZ‐1 phase III trial reported a survival benefit with the anti‐programmed death cell ligand 1 (anti‐PD‐L1) durvalumab in combination with gemcitabine and cisplatin in patients with ...advanced biliary tract cancer. The present study investigated the efficacy and safety of this new standard treatment in a real‐world setting.
Methods
The analysed population included patients with unresectable, locally advanced or metastatic adenocarcinoma of the biliary tract treated with durvalumab in combination with gemcitabine and cisplatin at 17 Italian centres. The primary endpoint of the study was progression‐free survival (PFS), whereas secondary endpoints included overall survival (OS), overall response rate (ORR) and safety. Unadjusted and adjusted hazard ratios (HRs) by baseline characteristics were calculated using the Cox proportional hazards model.
Results
From February 2022 to November 2022, 145 patients were enrolled. After a median follow‐up of 8.5 months (95% CI: 7.9–13.6), the median PFS was 8.9 months (95% CI: 7.4–11.7). Median OS was 12.9 months (95% CI: 10.9–12.9). The investigator‐assessed confirmed ORR was 34.5%, and the disease control rate was 87.6%. Any grade adverse events (AEs) occurred in 137 patients (94.5%). Grades 3–4 AEs occurred in 51 patients (35.2%). The rate of immune‐mediated AEs (imAEs) was 22.7%. Grades 3–4 imAEs occurred in 2.1% of the patients. In univariate analysis, non‐viral aetiology, ECOG PS >0 and NLR ≥3 correlated with shorter PFS.
Conclusion
The results reported in this first real‐world analysis mostly confirmed the results achieved in the TOPAZ‐1 trial in terms of PFS, ORR and safety.
Results are presented of a search for heavy stable charged particles produced in proton-proton collisions at s=13 TeV using a data sample corresponding to an integrated luminosity of 2.5 fb−1 ...collected in 2015 with the CMS detector at the CERN LHC. The search is conducted using signatures of anomalously high energy deposits in the silicon tracker and long time-of-flight measurements by the muon system. The data are consistent with the expected background, and upper limits are set on the cross sections for production of long-lived gluinos, top squarks, tau sleptons, and leptonlike long-lived fermions. These upper limits are equivalently expressed as lower limits on the masses of new states; the limits for gluinos, ranging up to 1610 GeV, are the most stringent to date. Limits on the cross sections for direct pair production of long-lived tau sleptons are also determined.
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