AIM To identify predictors for synchronous liver metastasis from resectable pancreatic ductal adenocarcinoma(PDAC) and assess unresectability of synchronous liver metastasis.METHODS Retrospective ...records of PDAC patients with synchronous liver metastasis who underwent simultaneous resections of primary PDAC and synchronous liver metastasis, or palliative surgical bypass, were collected from 2007 to 2015. A series of pre-operative clinical parameters, including tumor markers and inflammation-based indices, were analyzed by logistic regression to figure out predictive factors and assess unresectability of synchronous liver metastasis. Cox regression was used to identify prognostic factors in liver-metastasized PDAC patients after surgery, with intention to validate their conformance to the indications of simultaneous resections and palliative surgical bypass. Survival of patients from different groups were analyzed by the Kaplan-Meier method. Intra- and post-operative courses were compared, including complications. PDAC patients with no distant metastases who underwent curative resection served as the control group.RESULTS CA125 > 38 U/mL(OR = 12.397, 95%CI: 5.468-28.105, P < 0.001) and diabetes mellitus(OR = 3.343, 95%CI: 1.539-7.262, P = 0.002) independently predicted synchronous liver metastasis from resectable PDAC. CA125 > 62 U/mL(OR = 5.181, 95%CI: 1.612-16.665, P = 0.006) and age > 62 years(OR = 3.921, 95%CI: 1.217-12.632, P = 0.022) correlated with unresectability of synchronous liver metastasis, both of which also indicated a worse long-term outcome of liver-metastasized PDAC patients after surgery. After the simultaneous resections, patients with postoperatively elevated serum CA125 levels had shorter survival than those with post-operatively reduced serum CA125 levels(7.7 mo vs 16.3 mo, P = 0.013). The survival of liver-metastasized PDAC patients who underwent the simultaneous resections was similar to that of non-metastasized PDAC patients who underwent curative pancreatectomy alone(7.0 mo vs 16.9 mo, P < 0.001), with no higher rates of either pancreatic fistula(P = 0.072) or other complications(P = 0.230) and no greater impacts on length of hospital stay(P = 0.602) or post-operative diabetic control(P = 0.479).CONCLUSION The criterion set up by CA125 levels could facilitate careful diagnosis of synchronous liver metastases from PDAC, and prudent selection of appropriate patients for the simultaneous resections.
Pancreatic cancer is one of the most common gastrointestinal tumors, with its incidence staying at a high level in both the United States and China. However, the overall 5-year survival rate of ...pancreatic cancer is still extremely low. Surgery remains the only potential chance for long-term survival. Early diagnosis and precise staging are crucial to make proper clinical decision for surgery candidates. Despite advances in diagnostictechnology such as computed tomography(CT)and endoscopic ultrasound,diagnosis,staging and monitoring of the metabolic response remain a challenge for this devastating disease.Positron emission tomography/CT(PET/CT),a relatively novel modality,combines metabolic detection with anatomic information.It has been widely used in oncology and achieves good results in breast cancer,lung cancer and lymphoma.Its utilization in pancreatic cancer has also been widely accepted.However,the value of PET/CT in pancreatic disease is still controversial.Will PET/CT change the treatment strategy for potential surgery candidates?What kind of patients benefits most from this exam?In this review,we focus on the utility of PET/CT in diagnosis,staging,and assessment of resectability of pancreatic cancer.In addition,its ability to monitor metabolic response and recurrence after treatment will be emphasis of discussion.We hope to provide answers to the questions above,which clinicians care most about.
Abstract
The Parker Solar Probe (PSP) provides us with an unprecedentedly close approach to the observation of the Sun and hence the possibility of directly understanding the elementary process that ...occurs on the kinetic scale of particles' collective interaction in solar coronal plasmas. We report a type of weak solar radio burst (SRB) that was detected by PSP when it passed a low-density magnetic channel during its second encounter phase. These weak SRBs have a low starting frequency of ∼20 MHz and a narrow frequency range from a few tens of MHz to a few hundred kHz. Their dynamic spectra display a strongly evolving feature of the intermediate relative drift rate decreasing rapidly from above 0.01 s
−1
to below 0.01 s
−1
. Analyses based on common empirical models of solar coronal plasmas indicate that these weak SRBs originate from a heliocentric distance of ∼1.1–6.1
R
S
(the solar radius), a typical solar wind acceleration region with a low-
β
plasma, and that their sources have a typical motion velocity of ∼
v
A
(Alfvén velocity) obviously lower than that of the fast electrons required to effectively excite SRBs. We propose that solitary kinetic Alfvén waves with kinetic scales could be responsible for the generation of these small-scale weak SRBs, called solitary wave radiation.
AIM:To establish an orthotopic mouse model of pancreatic cancer that mimics the pathological features of exocrine pancreatic adenocarcinoma.METHODS:Pan02 cells were suspended in low-temperature ...Matrigel and injected into the parenchyma of pancreatic tails of C57BL/6 mice,with cells suspended in phosphate buffered saline(PBS)serving as a control.Primary and implanted tumors were confirmed pathologically.The rate of tumor formation and intraperitoneal implantation in the two groups were compared at different time points after injection.Leakage and intraabdominal dispersion of Matrigel and PBS,both dyed with methylene blue,were compared after injection into the parenchyma of the pancreas.We observed adherence and proliferation in Pan02 cells suspended in Matrigel in vitro.We also compared the pathological manifestation of this orthotopic pancreatic cancer model in the head and tails of the pancreas.The characteristics of the origin of epithelial cells and exocrine markers of established orthotopic pancreatic tumors were confirmed using immunohistochemistry.RESULTS:Diluted Matrigel could form a gel drip in the pancreatic parenchyma,effectively preventing leakage from the injection site and avoiding dispersion in the abdominal cavity.Pan02 cells were able to adhere to a dish,proliferate,and migrate in the gel drip.The tumor formation rate in the Matrigel group was 100%at both2 and 3 wk after injection,whereas it was 25.0%and37.5%in the PBS group at 2 and 3 wk,respectively(P<0.05).The intraperitoneal tumor implantation rate was 75.0%in the PBS group after 3 wk of injection,while it was 12.5%in the Matrigel group(P<0.05).Hepatoduodenal ligament and duodenal invasions with obstructive jaundice and upper digestive obstruction with mesenteric lymph node metastasis were observed in the pancreatic head group.In the pancreatic tail group,spleen and gastric invasion were dominant,leading to retroperitoneal lymph nodes metastasis.Positive immunohistochemical staining of cytokeratin and negative staining of vimentin and chromogranin A confirmed that the orthotopic pancreatic tumor injected with Pan02 cells suspended in Matrigel was of epithelial origin and expressed exocrine markers of cancer.CONCLUSION:This method of low-temperature Matrigel suspension and injection is effective for establishing an orthotopic mouse model of pancreatic cancer.
Purpose: This study investigated the mechanism of TSF in treating DN through network pharmacology, molecular docking, and experimental validation. Methods: To identify critical active ingredients, ...targets, and DN genes in TSF, multiple databases were utilized for screening purposes. The drug-compound-target network was constructed using Cytoscape 3.9.1 software for network topological analysis. The protein interaction relationship was analyzed using the String database platform. Metascape database conducted enrichment analysis on the key targets using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. The renoprotective effect was evaluated using a mouse model of diabetic nephropathy (db/db mice) that occurred spontaneously. Validation of the associated targets and pathways was performed using Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemical methods (IHC). Results: The network analysis showed that the TSF pathway network targeted 24 important targets and 149 significant pathways. TSF might have an impact by focusing on essential objectives such as TP53, PTEN, AKT1, BCL2, BCL2L1, PINK-1, PARKIN, LC3B, and NFE2L2, along with various growth-inducing routes. Our findings demonstrated that TSF effectively repaired the structure of mitochondria in db/db mice. TSF greatly enhanced the mRNA levels of PINK-1. WB and IHC findings indicated that TSF had a notable impact on activating the PINK-1/PARKIN signaling pathway in db/db mice, significantly increasing LC3 and NRF2 expression. Conclusion: Our results indicate that TSF effectively addresses DN by activating the PINK-1/PARKIN signaling pathway and enhancing Mitochondrion structure in experimental diabetic nephropathy. Keywords: tangshen formula, diabetes nephropathy, network pharmacology, mitophagy, PINK1/Parkin pathway
Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC), compared with genotype B. This study aims to investigate whether HBV genotypes influence the ...clinicopathologic features and long-term prognosis of patients after curative resection of HCC.
Stored serum samples from 62 patients with HBV-related HCC were tested for HBV genotype using a molecular method.
Sixty of 62 patients (96.8%) undergoing curative resection of HCC were infected with genotype B or C. Concomitant cirrhosis was encountered more frequently in patients with genotype C. During a mean follow-up period of 26.3 +/- 9.8 months, patients with genotype B had a lower overall tumor recurrence rate than those with genotype C (22% vs. 46%; P = 0.04). Stepwise multiple Cox proportional hazards regression analysis showed that multiplicity of tumor (hazard ratio, 6.84; 95% confidence interval CI, 1.45-32.2; P = 0.02) was associated with tumor recurrence, whereas genotype C and age were associated with borderline significance (P = 0.06). Stratified analysis showed that genotype C was still associated with tumor recurrence in cirrhotic patients with borderline significance by univariate analysis (hazard ratio, 3.8; 95% CI, 0.84-17.6; P = 0.07). However, cumulative 2-year survival rates were similar between patients with genotype B and C (92% vs. 85%; P = 0.23).
Our data suggest that patients with HCC with genotype C have a greater tumor recurrence rate after curative resection of HCC compared with those with genotype B. Prolonged follow-up is needed to clarify the impact of HBV genotype on postoperative outcome.
It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) ...patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus greater than or equal to5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio OR 0.70; 95% confidence intervals CI 0.30, 1.67, Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI 0.37, 1.83, Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range IQR, 50.0, 69.7 versus 55.0%, IQR 42.8, 63.8, Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR 12.8, 40.5), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio HR 0.74, 95% CI 0.50, 1.11, Log-rank p = 0.14). Grade greater than or equal to 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade greater than or equal to 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity.
The bending problem of a functionally graded anisotropic cantilever beam subjected to a linearly distributed load is investigated. The analysis is based on the exact elasticity equations for the ...plane stress problem. The stress function is introduced and assumed in the form of a polynomial of the longitudinal coordinate. The expressions for stress components are then educed from the stress function by simple differentiation. The stress function is determined from the compatibility equation as well as the boundary conditions by a skilful deduction. The analytical solution is compared with FEM calculation, indicating a good agreement.
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