The fifth version of the Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence‐based medicine and partly ...to the Grading of Recommendations Assessment, Development and Evaluation system, which was published in October 2021 in Japanese. In addition to surveillance–diagnostic and treatment algorithms, a new algorithm for systemic therapy has been created, as multiple drugs for hepatocellular carcinoma can be currently selected. Here, new or revised algorithms and evidence on which the recommendations are based are described.
Background
Age‐related events, such as cardiopulmonary complications, delirium, transfer to a rehabilitation facility, and dependency are a major problem after hepatic resection in the elderly. This ...prospective multicenter study aimed to preoperatively evaluate frailty in the elderly according to a phenotypic frail index, named the “Kihon Checklist (KCL),” to predict “age‐related events” after hepatic resection.
Methods
Between May 2016 and September 2017, 217 independently living patients who consented among all patients aged ≥65 years who planned to undergo hepatic resection were included in the study. Preoperative frailty was defined as a total KCL score ≥8. We analyzed clinical characteristics and outcomes, including age‐related events (major respiratory and cardiac complications, delirium medication needed, transfer to rehabilitation facility, and dependency) between patients with and without frailty.
Results
Of the 217 patients, 63 and 154 were classified into the frail and non‐frail groups, respectively. The incidences of age‐related events (31.7% vs. 7.8%, P < 0.001) were higher in the frail group. Multivariate analysis indicated that frailty (P < 0.001, hazard ratio 5.16) and resection of ≥2 sectors (P = 0.014, hazard ratio 2.98) were independent risk factors for age‐related events.
Conclusions
Frailty evaluated by KCL in the elderly can predict postoperative age‐related events after hepatic resection.
Highlight
In elderly patients scheduled to undergo hepatic resection, preoperative assessment of age‐related events, including respiratory complications, cardiac events, delirium, transfer to a rehabilitation facility and dependency, is essential. This prospective multicenter study by Tanaka and colleagues found that frailty evaluated by a phenotypic frailty index predicted age‐related events after hepatic resection.
Molecular hydrogen had been considered inactive in vivo but is an antioxidant that selectively reduces highly toxic reactive oxygen species (ROS). Animal studies have reported that hydrogen gas ...inhalation helped alleviate cerebral and cardiac ischemia-reperfusion injuries. In humans, hydrogen inhalation therapy is presently approved as a treatment under Advanced Medical Care B in Japan (jRCTs031180352: limited to adult patients who suffered out-of-hospital cardiac arrest and are in a continuous coma) and its effectiveness is being examined in a clinical trial. The Japanese government has introduced the "Advanced Medical Care System" to promote the development of drugs and devices under governmental regulations. Advanced Medical Care B is a system designed for unapproved or off-label drugs or medical technologies used in a clinical trial setting. Hepatectomy is generally performed with repeated hepatic blood-flow occlusion and then reperfusion (ischemia and reperfusion). No report, however, has been made on ROS inhibition by hydrogen inhalation therapy or its effectiveness in post-hepatectomy patients. Hydrogen gas inhalation in the early stages after hepatectomy is anticipated to inhibit liver dysfunction by inhibiting ROS.
This study is a randomized, controlled, double-blind superiority trial, which will be conducted as a "specified clinical trial" in accordance with the Clinical Trials Act in Japan. Trial registration was prospectively completed before the first participant was enrolled. The subjects will be patients who will undergo hepatectomy and will be allocated randomly into group A with hydrogen gas inhalation or group B with air inhalation after hepatectomy. The study will examine if hydrogen gas inhalation improves QOL of post-hepatectomy patients. The primary endpoint is patient QOL (score of a 40-item quality of recovery questionnaire, QoR40) on postoperative day 3 and the secondary endpoints are QoR40s besides that on postoperative day 3, grade of postoperative complications (Clavien-Dindo score), level of pain (Numerical Rating Scale (NRS)), amount of dietary intake, liver function, inflammation level, 8-hydroxydeoxyguanosine (urinary 8-OHdG) level, and number of pedometer-assessed steps.
The study protocol has been approved by the Niigata University Central Review Board of Clinical Research. The findings of this study will be widely disseminated through peer-reviewed publications and conference presentations.
jRCTs 03220332 . Registered on 21 January 2021.
Background
Adjuvant chemotherapy for resectable colorectal liver metastasis (CRLM) is widely used, but its efficacy lacks clear evidence. This retrospective cohort study investigated the ...effectiveness of neoadjuvant chemotherapy (NAC) compared to upfront surgery for CRLM.
Methods
Data from patients with resectable CRLM were analyzed. Short-term outcomes and long-term prognosis were analyzed using propensity score matching. CRLM was stratified according to the H-classification (H1 and H2), and the effectiveness of adjuvant chemotherapy was analyzed in each group.
Results
We analyzed 599 cases that were matched into an NAC group (
n
= 136) and an upfront surgery group (
n
= 136). The proportion of synchronous metastases, H2-classification, and postoperative chemotherapy rate did not differ between the groups. Overall survival (OS) after initial treatment was significantly worse in the NAC group than in the upfront surgery group (
P
= 0.029). The 5-, 7-, and 10-year OS rates for H1 patients were significantly better in the upfront surgery group than in the NAC group (64%, 51%, and 44% vs. 50%, 31%, and 18%, respectively) (
P
= 0.004).
Conclusion
Patients with resectable CRLM should undergo upfront surgery, because NAC did not improve OS after initial treatment in these patients.
The original difficulty scoring system was revised after discussion at the 2nd International Consensus Conference on Laparoscopic Liver Resection held in Morioka (Iwate Prefecture) in Japan and ...renamed the IWATE criteria (a 4-level classification system involving 6 preoperative factors). We used Japanese and French cohorts to validate the IWATE criteria by evaluating their association with the procedure-based difficulty classification proposed by the Institut Mutualiste Montsouris.
Patients who had undergone laparoscopic liver resection at multiple Japanese multi-institutions or the Institut Mutualiste Montsouris were assigned to the multiple Japanese multi-institution (n = 1,867) or Institut Mutualiste Montsouris cohort (n = 433). We analyzed clinical characteristics and outcomes according to the 4-level IWATE criteria difficulties (low, intermediate, advanced, and expert) and evaluated their association with 11 laparoscopic liver resection procedures in the Institut Mutualiste Montsouris classification (low, intermediate, and high levels).
We found significant differences in age, surgical indications, and the 4-level IWATE criteria difficulties between the cohorts (all, P < .001). Operation time and blood loss were significantly different among the 4-level difficulties in both cohorts (all, P < .001). The rates of conversion, postoperative complications, liver failure, and in-hospital deaths also increased significantly with increasing difficulty (all, P < .001). The IWATE criteria classified the three low-level Institut Mutualiste Montsouris procedures in the low-to-intermediate levels, the two intermediate-level procedures in the intermediate-to-advanced levels, and the six high-level procedures in the advanced-to-expert levels.
We observed associations between the IWATE criteria and intraoperative and postoperative outcomes in the Japanese multi-institution and Institut Mutualiste Montsouris cohorts and thus validated the IWATE system.
The crude drug
Sojutsu
, as defined by the Japanese Pharmacopoeia, is the rhizome of
Atractylodes lancea
De Candolle,
Atractylodes chinensis
Koidzumi, or their interspecific hybrids (Asteraceae).
...Sojutsu
is one of the traditional Kampo formulas, which are administered to patients suffering from stomach disorders, edema, and nephrotic syndrome. Although antiinflammatory effects of
Sojutsu
have been reported, its effects on the liver and kidney have not been extensively investigated. Here, we used a
Sojutsu
sample identified as
A. chinensis
rhizome and isolated several constituents from its ethyl acetate (EtOAc)-soluble fraction that decreased production of the proinflammatory mediator nitric oxide (NO) in interleukin 1β-treated rat hepatocytes. Among the constituents in this fraction, atractylodin showed the highest activity to suppress NO production, whereas hinesol, β-eudesmol, and α-bisabolol showed low activity. Atractylodin decreased the levels of inducible nitric oxide synthase, tumor necrosis factor α, and lipocalin 2 messenger RNAs (mRNAs). The EtOAc-soluble fraction of the
A. chinensis
rhizome extract was administered daily for 20 weeks to high immunoglobulin A (HIGA) mice, whose pathological findings resemble human immunoglobulin A nephropathy. This fraction decreased the weight of white adipose tissue and decreased mesangial proliferation and immunoglobulin A deposition in glomeruli. These results indicate that the EtOAc-soluble fraction, which included antiinflammatory constituents, may be responsible for improvement of the mesangial lesions in HIGA mice.
OBJECTIVE:We reviewed nationwide follow-up data to determine outcomes of different treatments for early-stage hepatocellular carcinoma (HCC) in elderly patients.
SUMMARY BACKGROUND DATA:Outcomes of ...early-stage HCC treatments in elderly patients have not been prospectively compared.
METHODS:We included 6490 HCC patients, aged ≥75 years at treatment, who underwent curative hepatic resection (HR, n = 2020), radiofrequency ablation (RFA, n = 1888), microwave ablation (MWA, n = 193), or transcatheter arterial chemoembolization (TACE, n = 2389), and compared their characteristics and survival. We used matching propensity score analysis (PSA) between the HR and RFA subgroups with tumors ≤3 cm to overcome baseline bias.
RESULTS:The HR group had significantly longer recurrence-free survival (RFS) than the RFA, MWA, and TACE groups RFA vs HR—hazard ratio1.22, 95% confidence interval (CI)1.09–1.37, P < 0.001; MWA vs HR—hazard ratio1.51, 95% CI1.22–1.88, P < 0.001; TACE vs HR—hazard ratio2.70, 95% CI2.44–2.99, P < 0.001). HR and RFA patients had significantly longer overall survival (OS) than the TACE group (RFA vs HR—hazard ratio1.01, 95% CI0.87–1.17, P = 0.919, TACE vs HR—hazard ratio2.11, 95% CI1.86–2.40, P < 0.001). PSA successfully matched HR and RFA patients from with primary HCC tumors ≤3.0 cm and similar liver function and tumor characteristics; and showed significantly longer RFS (hazard ratio1.64, 95% CI1.29–2.10, P < 0.001) and OS (hazard ratio1.57, 95% CI1.12–2.20, P = 0.009) for HR than for RFA (including subgroup analyses). In Cox proportional hazard analysis, HR offered better prognosis than RFA.
CONCLUSIONS:HR decreases recurrence risk and improves OS in patients aged ≥75 years with primary HCC tumors ≤3.0 cm.
Lactosomes™ are biocompatible nanoparticles that can be used for cancer tissue imaging and drug delivery. Lactosomes are polymeric micelles formed by the self-assembly of biodegradable amphiphilic ...block copolymers composed of hydrophilic polysarcosine and hydrophobic poly-L-lactic acid chains. The particle size can be controlled in the range of 20 to 100 nm. Lactosomes can also be loaded with hydrophobic imaging probes and photosensitizers, such as indocyanine green. Indocyanine green-loaded lactosomes are stable for long-term circulation in the blood, allowing for accumulation in cancer tissues. Such lactosomes function as a photosensitizer, which simultaneously enables fluorescence diagnosis and photodynamic therapy. This review provides an overview of lactosomes with respect to molecular design, accumulation in cancer tissue, and theranostics applications. The use of lactosomes can facilitate the treatment of cancers in unresectable tissues, such as glioblastoma and head and neck cancers, which can lead to improved quality of life for patients with recurrent and unresectable cancers. We conclude by describing some outstanding questions and future directions for cancer theranostics with respect to clinical applications.
Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. Oncolytic virus therapy is probably the next major breakthrough in cancer ...treatment. The third‐generation oncolytic herpes simplex virus type 1 (HSV‐1) T‐01 kills tumor cells without damaging the surrounding normal tissues. Here we investigated the antitumor effects of T‐01 on HCC and the host's immune response to HCC cells. The cytopathic activities of T‐01 were tested in 14 human and 1 murine hepatoma cell line in vitro. In various mouse xenograft models, HuH‐7, KYN‐2, PLC/PRF/5 and HepG2 human cells and Hepa1‐6 murine cells were used to investigate the in vivo efficacy of T‐01. T‐01 was cytotoxic to 13 cell lines (in vitro). In mouse xenograft models of subcutaneous, orthotopic and peritoneal tumor metastasis in athymic mice (BALB/c nu/nu), the growth of tumors formed by the human HCC cell lines and hepatoblastoma cell line was inhibited by T‐01 compared with that of mock‐inoculated tumors. In a bilateral Hepa1‐6 subcutaneous tumor model in C57BL/6 mice, the growth of tumors inoculated with T‐01 was inhibited, as was the case for contralateral tumors. T‐01 also significantly reduced tumor growth. T‐01 infection significantly enhanced antitumor efficacy via T cell‐mediated immune responses. Results demonstrate that a third‐generation oncolytic HSV‐1 may serve as a novel treatment for patients with HCC.
Multimodality therapies are used to manage patients with hepatocellular carcinoma (HCC), although advanced HCC is incurable. The third‐generation oncolytic herpes simplex virus type 1 (HSV‐1) T‐01 kills tumor cells without damaging the surrounding normal tissues. We examined the antitumor activities of T‐01 in HCC cell lines and mouse tumor xenograft models, and evaluated the host's immune response to HCC cells. Results demonstrate that a third‐generation oncolytic HSV‐1 may serve as a novel treatment for patients with HCC.
Dynamic assessment of preoperative exercise capacity may be a useful predictor of postoperative prognosis. We aimed to clarify whether perioperative exercise capacity was related to long-term ...survival in hepatocellular carcinoma patients with chronic liver injury undergoing hepatectomy. One hundred-six patients with hepatocellular carcinoma underwent pre- and postoperative cardiopulmonary exercise testing to determine their anaerobic threshold, defined as the point between carbon dioxide production and oxygen consumption per unit of time. Testing involved 35 items including blood biochemistry analysis, in-vivo component analysis, dual-energy X-ray absorptiometry, and cardiopulmonary exercise testing preoperatively and 6 months postoperatively. We classified patients with anaerobic threshold ≥ 90% 6 months postoperatively compared with the preoperative level as the maintenance group (n = 78) and patients with anaerobic threshold < 90% as the decrease group (n = 28). Five-year recurrence-free survival rates were 39.9% vs. 9.9% (maintenance vs. decrease group) (hazard ratio: 1.87 95% confidence interval: 1.12-3.13; P = 0.018). Five-year overall survival rates were maintenance: 81.9%, and decrease: 61.7% (hazard ratio: 2.95 95% confidence interval: 1.37-6.33; P = 0.006). Multivariable Cox proportional hazards models showed that perioperative maintenance of anaerobic threshold was an independent prognostic indicator for both recurrence-free- and overall survival. Although the mean anaerobic threshold from preoperative to postoperative month 6 decreased in the exercise-not-implemented group, the exercise-implemented group experienced increased anaerobic threshold, on average, at postoperative month 6. The significant prognostic factor affecting postoperative survival for chronic liver injury patients with HCC undergoing hepatectomy was maintenance of anaerobic threshold up to 6 months postoperatively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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