Prevalence, patterns, risk factors and outcomes of peritoneal metastases after laparoscopic hepatectomy for hepatocellular carcinoma: a multicenter study from China.

Background: We aim to investigate the prevalence, patterns, risk factors, and outcomes of peritoneal metastases (PM) after curative laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC). Methods: A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed. The incidence of PM following LH was evaluated and compared with that in open hepatectomy (OH) after 1:1 propensity score matching (PSM). Results: PM prevalence was 5.1% (15/295) in the early period [2010-2013], 2.6% (47/1,843) in the later period [2014-2016], and 2.9% (62/2,138) in all LH patients, which was similar to 4.0% (59/1,490) in the OH patients. The recurrence patterns, timing, and treatment did not significantly vary between the LH and OH patients (P>0.05). Multivariate logistic regression revealed that tumor diameter >5 cm, non-anatomical resection, presence of microvascular invasion, and lesions <2 cm from major blood vessels were independent risk factors of PM after LH. Of the 62 cases with PM, 26 (41.9%) had PM only, 34 (54.9%) had intrahepatic recurrence (IHR) and PM, and 2 (3.2%) had synchronous extraperitoneal metastases (EPM). Patients with resectable PM had a 5-year overall survival (OS) of 65.0% compared to 9.0% for unresectable PM (P=0.001). Conclusions: The prevalence, patterns and independent risk factors of PM were identified for HCC patients after LH. LH was not associated with increased incidence of PM in HCC patients for experienced surgeons. Surgical re-excision of PM was associated with prolonged survival.

International experts consensus guidelines on robotic liver resection in 2023.

The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

Cancer-associated fibroblast-secreted miR-421 promotes pancreatic cancer by regulating the SIRT3/H3K9Ac/HIF-1α axis.

This study was designed to explore the effects of exosomal miR-421 secreted by cancer-associated fibroblasts (CAFs) on pancreatic cancer (PC) progression and the mechanisms involved. CAFs and exosomes (exos) were isolated and identified. PC cells were treated with CAF-derived exos (CAF-exos). Western blotting and quantitative polymerase chain reaction (qPCR) were used to measure miR-421, sirtuin-3 (SIRT3), and hypoxia duciblefactors-1 alpha (HIF-1α) levels. Cell counting kit-8 (CCK-8), wound-healing, and transwell migration assays were used to measure proliferation, migration, and invasion abilities of the cells. Dual-luciferase assay and RNA immunoprecipitation (RIP) experiment analyzed the relationship between miR-421 and SIRT3. Chromatin immunoprecipitation (f)-verified H3K9Ac enrichment in the HIF-1α promoter region. In vivo tumorigenesis experiments were performed to further explore the effects of exosomal miR-421 from CAFs on PC. CAFs and exos were successfully isolated. CAF-exo-treated PC cells highly expressed miR-421 and had increased cell proliferation, migration, and invasion abilities. Knocking down miR-421 increased the expression of SIRT3. SIRT3 is a target of miR-421, and inhibiting the expression of SIRT3 reversed the negative effects of miR-421 knockdown on PC cell. Knocking down miR-421 in CAF-exo inhibited the expression of HIF-1α in PC cells. Moreover, SIRT3-mediated HIF-1α expression by regulating H3K9Ac. HIF-1α overexpression reversed the inhibiting effects of SIRT3 overexpression on PC progression and counteracted the inhibiting effects of miR-421 knockdown on glycolysis. Moreover, in vivo tumorigenesis experiments showed that knocking down miR-421 attenuated CAF-exo induced tumor growth. Exosomal miR-421 from CAFs promoted PC progression by regulating the SIRT3/H3K9Ac/HIF-1α axis. This study provided insights into the molecular mechanism of PC.

LINC00960 regulates cell proliferation and glycolysis in pancreatic cancer through the miR-326-3p/TUFT1/AKT-mTOR axis.

Pancreatic cancer (PC) is a common malignant cancer characterized by high mortality and poor prognosis. LINC00690 was involved in the occurrence and progression of PC, but the underlying mechanisms require further investigation. The goal of this study was to figure out how LINC00960 mediates glycolysis in PC. LINC00960, miR-326-3p, and Tuftelin 1 (TUFT1) expression levels were detected in PC cell lines. LINC00960 and TUFT1 expression levels were increased in PC cells when compared with normal pancreatic cells, whereas miR-326-3p expression levels were decreased. The expression levels of LINC00690 affected glycolysis in PC, and inhibition of LINC00960 inhibited tumor growth in vivo. LINC00690 targeted and suppressed the expression of miR-326-3p. MiR-326-3p bound to TUFT1, and miR-326-3p inhibited AKT-mTOR pathway activation via TUFT1. In conclusion, the depletion of LINC00960 repressed cell proliferation and glycolysis in PC by mediating the miR-326-3p/TUFT1/AKT-mTOR axis. Thus, we present a novel mechanism underlying the progression of PC that suggests LINC00960 is a potential therapeutic target for this cancer.

International consensus statement on robotic hepatectomy surgery in 2018.

The robotic surgical system has been applied in liver surgery. However, controversies concerns exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. To promote the development of robotic hepatectomy, this study aimed to evaluate the current status of robotic hepatectomy and provide sixty experts' consensus and recommendations to promote its development. Based on the World Health Organization Handbook for Guideline Development, a Consensus Steering Group and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 22 topics were prepared analyzed and widely discussed during the 4 meetings. Based on the published articles and expert panel opinion, 7 recommendations were generated by the GRADE method using an evidence-based method, which focused on the safety, feasibility, indication, techniques and cost-effectiveness of hepatectomy. Given that the current evidences were low to very low as evaluated by the GRADE method, further randomized-controlled trials are needed in the future to validate these recommendations.

Design and optimization of highly nonlinear low-dispersion crystal fiber with high birefringence for four-wave mixing.

We have proposed a novel type of photonic crystal fiber (PCF) with low dispersion and high nonlinearity for four-wave mixing. This type of fiber is composed of a solid silica core and a cladding with a squeezed hexagonal lattice elliptical airhole along the fiber length. Its dispersion and nonlinearity coefficient are investigated simultaneously by using the full vectorial finite element method. Numerical results show that the proposed highly nonlinear low-dispersion fiber has a total dispersion as low as +/-2.5 ps nm(-1) km(-1) over an ultrabroad wavelength range from 1.43 to 1.8 microm, and the corresponding nonlinearity coefficient and birefringence are about 150 W(-1) km(-1) and 2.5x10(-3) at 1.55 microm, respectively. The proposed PCF with low ultraflattened dispersion, high nonlinearity, and high birefringence can have important application in four-wave mixing.

Surgical treatment and prognostic analysis of 93 cases of hilar cholangiocarcinoma.

OBJECTIVE: To explore the surgical treatment and prognosis of hilar cholangiocarcinoma. METHODS: This was a retrospective study of 93 cases of hilar cholangiocarcinoma that were treated surgically at our hospital from June 1999 to June 2005. Prognostic factors were also analyzed. RESULTS: Fifty-two cases were treated with curative resection, 21 with palliative resection, and 9 with nonoperative drainage. Eleven cases underwent palliative drainage operations. The median survive time was 31 months in the curative resection group, 13.7 months in the palliative resection group, and 11 months in the nonoperative drainage group. Patient age, serum total bilirubin, clinical type of Bismuth-Corlette, tumor differentiation, and lymph node metastases were important factors for predicting the prognosis of hilar cholangiocarcinoma. CONCLUSIONS: Resection was the main treatment for hilar cholangiocarcinoma, and curative resection was the best way to obtain better prognosis. Age, preoperative serum total bilirubin, bismuth clinical type, tumor histopathological grading, and lymph node metastases were considered to have a significant effect on prognosis.

Clinical value of serum CA19-9 levels in evaluating resectability of pancreatic carcinoma.

AIM: To evaluate the clinical value of serum CA19-9 levels in predicting the respectability of pancreatic carcinoma according to receiver operating characteristic (ROC) curve analysis. METHODS: Serum CA19-9 levels were measured in 104 patients with pancreatic cancer which were possible to be resected according to the imaging. ROC curve was plotted for the CA19-9 levels. The point closest to the upper left-hand corner of the graph were chosen as the cut-off point. The sensitivity, specificity, positive and negative predictive values of CA19-9 at this cut-off point were calculated. RESULTS: Resectable pancreatic cancer was detected in 58 (55.77%) patients and unresectable pancreatic cancer was detected in 46 (44.23%) patients. The area under the ROC curve was 0.918 and 95% CI was 0.843-0.992. The CA19-9 level was 353.15 U/mL, and the sensitivity and specificity of CA19-9 at this cut-off point were 93.1% and 78.3%, respectively. The positive and negative predictive value was 84.38% and 90%, respectively. CONCLUSION: Preoperative serum CA19-9 level is a useful marker for further evaluating the resectability of pancreatic cancer. Obviously increased serum levels of CA19-9 (> 353.15 U/mL) can be regarded as an ancillary parameter for unresectable pancreatic cancer.

Accumulation of beta-catenin protein, mutations in exon-3 of the beta-catenin gene and a loss of heterozygosity of 5q22 in solid pseudopapillary tumor of the pancreas.

BACKGROUND: Solid pseudopapillary tumors (SPT) of the pancreas are neoplasms with a low malignant potential. The molecular events contributing to the pathogenesis of SPTs are still unknown. OBJECTIVES: This study was intended to help better understand the early steps of human SPT development. METHODS: We microdissected 20 SPTs and normal pancreatic tissue. In addition, we examined the DNA from each SPT for mutations in exon-3 of beta-catenin and loss of heterozygosity (LOH) on 9 chromosome arms using 10 microsatellite markers. Immunohistochemical staining for beta-catenin was performed. RESULTS: Activating mutations between codons 32 and 37 of beta-catenin exon-3 were present in 16 cases (80%). Allelic loss on chromosome 5q22.1 was present in 10 cases (55.5%), while no allelic loss was found on chromosomes 1p, 6q, 9p, 9q, 11p, 11q, 17p, or 22q. Nuclear accumulation of beta-catenin was found in 20 cases (100%). CONCLUSION: Mutations in exon-3 of the beta-catenin gene, nuclear accumulation of beta-catenin, and LOH on chromosome 5q22.1 in SPT tissue suggest that these mutations are involved in SPT tumorigenesis.

Solid-pseudopapillary tumours of the pancreas: 14 years experience.

BACKGROUND: Solid-pseudopapillary tumour of the pancreas (SPTP) is a low-grade malignancy lesion that is distinct from other pancreatic tumours. Preoperative diagnosis is often inaccurate and treatment strategies remain controversial. The present study reviews the clinical features, diagnosis, treatment, and outcome of Asian patients with SPTP from a single institution. METHODS: The medical records and images of patients who underwent surgery for SPTP between June 1990 and December 2003 were retrospectively reviewed. Study eligibility required that patients had undergone surgical resections and that the SPTP had been pathologically demonstrated. RESULTS: Twenty-eight patients with SPTP were identified. Eighteen patients (64.3%) reported the predominant symptom of 'vague abdominal pain', five patients (17.8%) had an apparent 'abdominal mass', and five patients (17.8%) without overt symptoms had masses that were discovered incidentally during screening. All patients underwent magnetic resonance (MR) imaging (n = 22) and/or computed tomography (n = 17), with a specificity of 90.9% and 76.4%, respectively. All masses were well-circumscribed, except for a tumour in one patient (3.6%), which adhered to the stomach wall and metastasized to the liver. Two patients (7.1%) underwent enucleation, while 25 patients (89.3%) received curative resection. The patient with the liver metastases underwent distal pancreatectomy and splenectomy with partial hepatectomy. The mean follow up was 66.9 months. No mortality occurred during follow up but the patient with the liver metastasis had progressive deterioration. CONCLUSION: Symptoms of SPTP are indistinct and preoperative diagnosis is often inaccurate. Magnetic resonance imaging improves SPTP diagnosis. In general, the prognosis of well-circumscribed SPTP is favourable after curative resection.

Laparoscopic cholecystectomy for treatment of unexpected early-stage gallbladder cancer.

BACKGROUND AND OBJECTIVES: Laparoscopic cholecystectomy (LC) may result in the incidental diagnosis of early stage (T1 and T2) gallbladder cancer. LC is useful for T1 patients, however, its role in T2 patients remains controversial. We sought to determine the effect of initial LC on patient outcome in early-stage gallbladder cancer. METHODS: Twenty-nine patients with T1 or T2 disease were reviewed retrospectively to assess preoperative diagnosis, intraoperative findings, and outcomes. RESULTS: Diagnoses included gallbladder stones (5), gallstones with polyps (5), and gallbladder polyps (19). Malignancy was suspected in 15 patients (14 polyp lesions and 1 gallbladder stone with wall thickening). After frozen sections, two T2 patients were immediately treated with radical operation owing to positive margins. Of 14 patients diagnosed by pathology, 4 T2 patients with positive margins underwent a second radical operation. Five-year survival rate was 100% and 49.6 % (T1 and T2 patients). No mortality or recurrence was detected in T1 patients (mean follow-up, 45.8 months; range, 6-98 months). Three T2 patients died, and one T2 patient relapsed after LC. No port site metastasis was detected. CONCLUSIONS: LC for T1a and T1b gallbladder cancer needs no additional treatment, however, radical operation for T2 patients is recommended, regardless of the margin condition.