Palladium-Catalyzed Inward Isomerization Hydroaminocarbonylation of Alkenes.

In contrast to the kinetically favored outward isomerization-hydrocarbonylation of alkenes, the disfavored inward isomerization-hydrocarbonylation of alkenes remains an important challenge. Herein, we have developed a novel and effective palladium-catalyzed inward isomerization-hydroaminocarbonylation of unactivated alkenes and aniline hydrochlorides for the formation of synthetically valuable α-aryl carboxylic amides in high yields and high site-selectivities. The high efficiency of the reaction is attributed to a relay catalysis strategy, in which the Markovnikov-favored [PdH]-PtBu3 catalyst is responsible for inward isomerization, while the [PdH]-Ruphos catalyst is responsible for hydroaminocarbonylation of the resulting conjugated aryl alkenes. The reaction exhibits highly functional group tolerance and provides a new method for formal carbonylation of remote C(sp3)-H bond.

Efficacy and safety of drug-eluting bead transarterial chemoembolization (DEB-TACE) combined with tyrosine kinase inhibitors (TKIs) in patients with unresectable hepatocellular carcinoma (uHCC): A systematic review and meta-analysis.

BACKGROUND: The optimal management of unresectable hepatocellular carcinoma (uHCC) remains an unresolved challenge. There is ongoing debate regarding the efficacy and safety of drug-eluting bead TACE (DEB-TACE) with tyrosine kinase inhibitors (TKIs). METHODS: We searched PubMed, Embase, Web of Science and the Cochrane Library for eligible studies. The main endpoints under investigation were survival outcomes, including overall survival (OS), progression-free survival (PFS), and time to progression (TTP). Secondary outcomes encompassed tumor response rates and adverse events (AEs). Two researchers conducted the data extraction independently and assessed the quality of the studies. After pooling and analyzing the data, we assessed the heterogeneity and performed both subgroup analysis and sensitivity analysis. Additionally, we evaluated the potential for publication bias. RESULTS: Eight studies with 1513 patients were finally retrieved. Compared to monotherapy, although bigeminal therapy exhibited improved survival benefits (OS: HR: 0.56, 95 % CI 0.41-0.76, p < 0.001; TTP: HR: 0.72, 95 % CI 0.59-0.87, p = 0.001) and tumor response (ORR: RR: 1.59; 95 % CI 1.19-2.13, p = 0.002; DCR: RR: 1.14; 95 % CI 1.03-1.26, p = 0.010), the reliability of results was affected by significant heterogeneity. In the subgroup analysis, compared to DEB-TACE alone, the bigeminal therapy failed to show any statistical differences. Compared to TKIs, it demonstrated significant advantages in both survival (OS: HR: 0.49, 95 % CI 0.40-0.61, p < 0.001; TTP: HR: 0.60, 95 % CI 0.48-0.75, p < 0.001) and tumor response (ORR: RR: 2.40, 95 % CI 1.86-3.09, p < 0.001; DCR: RR: 1.36, 95 % CI 1.20-1.54, p < 0.001) while low heterogeneity was observed. Concerning safety, DEB-TACE provides no more severe AEs while TKIs-related AEs require close monitoring. CONCLUSION: Our findings suggest that DEB-TACE combined with TKIs may be a safe and effective treatment for uHCC, which is more suitable for patients in the advanced stage.

Transhepatic arterial approaches for ICG injection to guide laparoscopic anatomical hepatectomy: A case series study.

BACKGROUND: Laparoscopic anatomical hepatectomy guided by near-infrared fluorescence imaging (NIR-FI) has been utilized extensively. However, it is difficult to resect "cone units" above the third branch of the Glissonean pedicle in the right posterior lobe using the laparoscopic positive or negative staining techniques. Therefore, we undertook a new laparoscopic segmentectomy based on the concept of "cone unit" assisted by interventional radiology combined with NIR-FI. METHODS: Laparoscopic segmentectomy guided by NIR-FI via super-selective hepatic arteriography and trans-arterial injection of ICG was carried out on 13 patients with early-stage HCC between September 2020 and January 2022.11 of cases were successful, and relevant pathological characteristics and perioperative outcomes were retrospectively analyzed. RESULTS: Two cases failed NIR-FI out of which one case involved over-staining to the non-target segment, and in the other case, which was to undergo laparoscopic segment V resection, only the ventral segment was stained while the imaging of the dorsal segment failed. In the intraoperative conditions, the tumor safe margin was 1.1 (0.7-1.55) cm, the interventional operation time was 50 (45.5-60.5) minutes, the operation time was 280 (242.5-307.5) minutes, the blood loss was 100 (50-200) ml, the postoperative hospital stay was 5 (4.5-5.5) days. No cases converted to laparotomy, and no serious postoperative complications developed. CONCLUSIONS: NIR-FI through super-selective hepatic arteriography and trans-arterial injection of ICG can provide a clear and lasting navigation aid for laparoscopic segmentectomy, which may have positive implication for early-stage HCC with poor preoperative liver reserves.

Safety and efficacy of laparoscopic transperitoneal versus retroperitoneal resection for benign retroperitoneal tumors: a retrospective cohort study.

BACKGROUND AND OBJECTIVE: Benign retroperitoneal tumors (BRTs) are clinically rare solid tumors. This study aimed to compare the safety and efficacy of laparoscopic transperitoneal versus retroperitoneal resection for BRTs. METHODS: The clinical data of 43 patients who had pathologically confirmed BRTs and underwent laparoscopic resection in a single center from January 2019 to May 2022 were retrospectively analyzed. Patients were divided into two groups according to the surgical methods: the Transperitoneal approach group (n = 24) and the Retroperitoneal approach group (n = 19). The clinical characteristics and perioperative data between the two groups were compared. The baseline data and surgical variables were analyzed to determine the impact of different surgical approaches on the treatment outcomes of BRTs. RESULTS: No significant difference was observed between the two groups in gender, age, body mass index, the American Society of Anesthesiologists score, presence of underlying diseases, tumor size, tumor position, operation duration, intraoperative hemorrhage, postoperative hospital stay, intestinal function recovery time, and postoperative complication rate. The conversion rate from laparoscopic to open surgery was significantly lower in the Transperitoneal approach group than in the Retroperitoneal approach group (1/24 vs. 5/19, χ2 = 4.333, P = 0.037). Tumor size was an independent influencing factor for the effect of surgery (odds ratio = 1.869, 95% confidence interval = 1.135-3.078, P = 0.014) and had a larger efficacy on the retroperitoneal group (odds ratio = 3.740, 95% confidence interval = 1.044-13.394, P = 0.043). CONCLUSION: The laparoscopic transperitoneal approach has the inherent advantages of anatomical hierarchies and surgical space, providing a better optical perspective of the targeted mass and improved bleeding control. This approach may have better efficacy than the retroperitoneal approach, especially in cases of a large tumor or when the tumor is located near important blood vessels.

Liver transplantation versus resection for patients with combined hepatocellular cholangiocarcinoma: A retrospective cohort study.

Background: Combined hepatocellular cholangiocarcinoma (CHC) is a rare primary liver cancer, and whether liver transplantation should be implemented among CHC patients is still controversial. We intend to conduct a retrospective cohort study based on the Surveillance, Epidemiology, and End Results (SEER) database to investigate the prognosis of liver transplantation vs. liver resection among CHC patients. Methods: Patients diagnosed with CHC (ICD-O-3:8180/3) and treated with transplantation or hepatectomy were extracted from the SEER database (2000-2018). We utilized Propensity Score Matching to control confounding bias. Kaplan-Meier curve was used for survival analysis, and Cox regression was used to find independent factors associated with prognosis. Results: We identified 123 (transplantation: 49; resection: 74) patients with CHC who were treated between 2004 and 2015. In the entire cohort, survival analysis demonstrated transplantation group was associated with better overall survival and cancer-specific survival (log-rank p = 0.004 and p = 0.003, respectively). In addition, liver transplantation still conferred better overall and cancer-specific survival than liver resection after Propensity Score Matching (log-rank p = 0.024 and p = 0.048, respectively). However, this advantage didn't appear in the subgroup, regardless of whether the tumor size was greater than 3 cm or not. (≤3 cm: OS log-rank p = 0.230, CSS log-rank p = 0.370; >3 cm: OS log-rank p = 0.110, CSS log-rank p = 0.084). Multivariate analysis validated the finding that liver transplantation was a protective factor for overall survival (HR = 0.55 [0.31-0.95], p = 0.032). Conclusions: Liver transplantation may be an option in individuals with CHC and should be taken into consideration due to its advantages in terms of overall survival and cancer-specific survival. However, a sizable sample is required for future studies to determine which subset of CHC patients may benefit more from liver transplantation.

Surgical indications for solid hepatic benign tumors: An updated literature review.

Hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma are the most common benign solid liver tumors. However, their surgical indications have been the subject of debate. Minimally invasive liver resection reduces the cost of surgery and may lead to overtreatment of benign liver tumors. Recently, there has been a growing understanding of the etiology, pathogenesis, and natural history of these tumors. Great progress has also been made in imaging. The use of MRI and contrast agents has improved the accuracy of non-invasive diagnosis of these tumors, and especially in the identification of specific molecular subtypes of liver adenoma. These factors have resulted in alterations of surgical indications for these tumors. This article examines recent literature and it discusses the surgical indications for hepatic hemangioma, focal nodular hyperplasia, and hepatic adenoma while summarizing modifications in clinical management.

The prophylactic role of mitomycin C-based hyperthermic intraperitoneal chemotherapy (MMC-based HIPEC) on peritoneal metastasis of spontaneously ruptured hepatocellular carcinoma (srHCC): A pilot study.

Hepatocellular carcinoma (HCC) was featured as spontaneous rupture hemorrhage under intratumoral overpressure. Spontaneous rupture hepatocellular carcinoma (srHCC) has a high propensity for peritoneal metastasis (PM). Although HIPEC has become standard treatment for malignancies with PM, it has been poorly described in srHCC. We conducted a single-arm, open-label, single-center, prospective study to explore the prophylactic role of MMC-based HIPEC on PM of srHCC. A total of 7 patients were collected from April 1, 2021 to April 30, 2022. HIPEC was conducted 3 times on the first, third and fifth postoperative days. 15 mg/m2 of MMC was used with 60 minutes perfusion at 43°C. The primary end-point was local peritoneum recurrence free survival (RFS), whereas the secondary end-point was systemic RFS and overall survival (OS). The mean hepatectomy operation time was 232 minutes (SD: 124.08 minutes). The median bleeding loss was 200 mL (range 50-400 mL). The mean hospital stay was 13 days (SD: 3.42 days). Only mild abdominal distension was reported in 4 patients (57%). There were no patients who suffered from life-threatening intra-abdominal and extra-abdominal complications (EAC). At the data cut-off (April 30, 2023), one patient (14%) had died due to cachexia. Local peritoneal recurrence occurred in three patients (43%). Median follow-up was 16.1 months (IQR: 12.8-16.6 months). Median local peritoneum RFS was 12.3 months (95% CI: 7.0- 17.5; 4 events) and median overall RFS was 7.5 months (95% CI: 4.2-10.8; 6 events). MMC-based HIPEC was safe and feasible in selected patients of srHCC. It showed a positive tendency in preventing PM, but large-scale research should be continued.

Acupuncture decreases amygdala functional connectivity in subjective tinnitus.

Introduction: Subjective tinnitus is a common and intractable ear disease. The effectiveness of acupuncture in the treatment of subjective tinnitus has been confirmed, but its mechanism of action is not clear. The structures of the amygdala (AMYG) are mainly closely related to emotion in the human brain. This study aimed to investigate the changes in functional connectivity (FC) of AMYG in subjective tinnitus to elucidate the neural mechanism of acupuncture. Methods: Correlation scale scores of 26 patients with subjective tinnitus were collected, including Tinnitus Evaluation Questionnaire (TEQ), Tinnitus Handicap Inventory (THI) and Visual Analog Scale (VAS). Meanwhile, rs-fMRI data were collected before and after acupuncture treatment in the patients, and in healthy controls (HC) matching the patient's gender and age. Then, AMYG was selected as region of interest to perform FC analysis. Finally, FC patterns of AMYG were first compared between patients with subjective tinnitus and HC, and then within subjects pre-acupuncture and post-acupuncture. Simple linear regression models between correlation scale scores and FC-values were established as well. Results: Acupuncture treatment relieved the severity of tinnitus. With the acupuncture treatment, the total THI score, TEQ score, and VSA score of patients were significantly lower than before (p < 0.05). Compared with HC, FC of tinnitus patients between AMYG and right inferior temporal gyrus and right precuneus significantly decreased before acupuncture (voxel p < 0.001, cluster p < 0.05, corrected with GRF), while FC of tinnitus patients between AMYG and left superior frontal gyrus and right superior temporal gyrus significantly decreased after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). FC of tinnitus patients between the AMYG and right superior frontal gyrus and left paracingulate gyrus showed significant decrease after acupuncture treatment (voxel p < 0.001, cluster p < 0.05, corrected with GRF). Besides, the linear regression models of the effect of THI on FC and VAS on FC performed were statistically significant (p < 0.05). Discussion: The findings demonstrate that acupuncture can decrease FC of AMYG, which could be positively correlated with the relief of tinnitus symptoms. This result suggests that acupuncture stimulation can effectively relieve the severity of tinnitus by decreasing FC of AMYG in subjective tinnitus patients.

Liver transplantation in China: Achievements over the past 30 years and prospects for the future.

Over the last three decades, liver transplantation (LT) in China has made breakthroughs from scratch. Now, new techniques are being continuously incorporated. However, LT in China differs from that in other countries due to cultural differences and the disease burden. The advances made in and the current issues with LT in China need to be summarized. Living donor LT (LDLT) has developed dramatically in China over the last 30 years, with the goal of increasing transplant opportunities and dealing with the shortage of donors. Western candidate selection criteria clearly are not appropriate for Chinese patients. Thus, the current authors reviewed the literature, and this review has focused on the topics of technological advancements in LDLT and Chinese candidate selection. The Milan criteria in wide use emphasize tumor morphology rather than pathology or biomarkers. α-fetoprotein (AFP) and pathology were incorporated as predictors for the first time in the Hangzhou criteria. Moreover, Xu et al. divided the Hangzhou criteria into type A (tumor size ≤ 8 cm or tumor size > 8 cm but AFP ≤ 100 ng/mL) and type B (tumor size > 8 cm but AFP between 100 and 400 ng/mL), with type B serving as a relative contraindication in the event of a liver donor shortage. In addition, surgeons in Chengdu and Shanghai have the ability to perform a laparoscopic hepatectomy for right and left lobe donors, respectively. China has established a complete LT system, including recipient criteria suitable for Chinese people, a fair donor allocation center, a transplant quality monitoring platform, and mature deceased donor or living donor LT techniques.

Trocar layouts in laparoscopic liver surgery.

BACKGROUND: Since the first laparoscopic wedge resection reported by Reich, laparoscopic liver resection (LLR) has been progressively developed, acquiring safety and feasibility. The time has witnessed a milestone leap for laparoscopic hepatectomy from pure laparoscopic partial hepatectomy to anatomical hepatectomy and from minor liver resection to major liver resection. The numerous previous studies have paid more attention to the short-time and long-time surgical outcomes caused by surgical techniques corresponding to various segments and approaches. However, focus on trocar layouts remains poorly described, but it plays an indispensable role in surgical process. METHODS: We have searched PubMed for English language articles with the key words "trocar," "laparoscopic liver resection," and "liver resection approaches." RESULTS: This review highlighted each type of trocar layouts corresponding to specific circumstances, including targeted resection segments with various approaches. Notably, surgeon preferences and patients body habitus affect the trocar layouts to some extent as well. CONCLUSIONS: Although there were fewer researches focus on trocar layouts, they determine the operation field and manipulation space and be likely to have an impact on outcomes of surgery. Therefore, further studies are warranted to firm the role of trocar layouts in LLR.

Use of chemotherapy to treat hepatocellular carcinoma.

Hepatic malignancies remain a global challenge. Hepatocellular carcinoma (HCC) accounts for around 90% of patients with liver cancer and is the sixth most common neoplasm worldwide and the fourth leading cause of cancer-related death. However, the long-term prognosis for HCC remains far from satisfactory, with a late diagnosis and limited treatment. DOX has served as conventional chemotherapy with the longest history of use. Although conventional chemotherapy is being challenged by molecular therapy and immune therapy, there is renewed optimism and interest in both systematic and locoregional therapy. Combined chemotherapy is widely used in clinical practice. In specific terms, FOLFOX can serve as a first-line (category 2B) option as recommended by the 2021 NCCN guidelines, while the efficacy of LTLD plus RFA has been confirmed in the phase III HEAT study. These approaches have challenged the dominant status of molecular therapy in terms of health economics and they have potential benefits in Asia, where HBV-related hepatocellular carcinoma is prevalent. Moreover, locoregional chemotherapy can be achieved with TACE and HAIC (possibly involving FOLFOX, DOX, mitomycin C, cisplatin, epirubicin, etc.). TACE was officially recommended by the 2021 NCCN guidelines for patients with Child-Pugh class B liver disease. In addition, HAIC has demonstrated a potential advantage in preliminary clinical practice, although it hasn't been included in any guidelines. Hence, this review summarizes large-scale trials and studies examining the development and innovative use of chemotherapeutic agents. Mounting clinical evidence warrants an exploration of the efficacy of chemotherapy.

The multidisciplinary management of hepatocellular carcinoma with portal vein tumor thrombus.

Portal vein tumor thrombus (PVTT) is one of the most common complications of hepatocellular carcinoma (HCC), which refers to the advanced stage of HCC and indicates an extremely poor prognosis. Monotherapy cannot effectively prolong the survival benefit of patients with HCC-PVTT characterized by a high recurrence rate. With great progress in the area of immune and molecular targeted therapy, there comes a promising era of multidisciplinary management of HCC. Survival benefits can be achieved based on accurate diagnosis, staging, and multidisciplinary management. Additionally, in terms of the presence of controversy about the standard treatment algorithm and the absence of universal treatment guidelines, a multidisciplinary management program may afford the best hope for HCC-PVTT patients via appropriate implement of various treatment protocols.

Interpretation of guidelines for the diagnosis and treatment of primary liver cancer (2019 edition) in China.

Primary liver cancer (PLC) is currently the fourth most common malignancy and accounts for the second most cancer-related deaths in China. Since 2017, a great deal of high-level evidence, and particularly evidence based on Chinese studies and practice, has emerged in terms of diagnosis, staging, and treatment. A new version of the guidelines for the management of PLC specifying the diagnosis and treatment of PLC (2019 edition) has recently been published. The guidelines feature major changes in the techniques for early diagnosis, the combination of surgery, local therapy, and systemic treatment, and the use of traditional Chinese medicine. The guidelines need to be further implemented in clinical practice to demonstrate their validity.