Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

Textbook outcome in gallbladder carcinoma after curative-intent resection: a 10-year retrospective single-center study / 中华医学杂志(英文版)

BACKGROUND@#Textbook outcome (TO) can guide decision-making among patients and clinicians during preoperative patient selection and postoperative quality improvement. We explored the factors associated with achieving a TO for gallbladder carcinoma (GBC) after curative-intent resection and analyzed the effect of adjuvant chemotherapy (ACT) on TO and non-TO patients.@*METHODS@#A total of 540 patients who underwent curative-intent resection for GBC at the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to December 2020 were retrospectively analyzed. Multivariable logistic regression was used to investigate the factors associated with TO.@*RESULTS@#Among 540 patients with GBC who underwent curative-intent resection, 223 patients (41.3%) achieved a TO. The incidence of TO ranged from 19.0% to 51.0% across the study period, with a slightly increasing trend over the study period. The multivariate analysis showed that non-TO was an independent risk factor for prognosis among GBC patients after resection ( P = 0.003). Age ≤60 years ( P = 0.016), total bilirubin (TBIL) level ≤34.1 μmol/L ( P <0.001), well-differentiated tumor ( P = 0.008), no liver involvement ( P <0.001), and T1-2 stage disease ( P = 0.006) were independently associated with achieving a TO for GBC after resection. Before and after propensity score matching (PSM), the overall survival outcomes of non-TO GBC patients who received ACT and those who did not were statistically significant; ACT improved the prognosis of patients in the non-TO group ( P <0.05).@*CONCLUSION@#Achieving a TO is associated with a better long-term prognosis among GBC patients after curative-intent resection, and ACT can improve the prognosis of those with non-TO.

Underlying targets and mechanism of taohong siwu decoction in prosthetic joint infection on network pharmacology / 中国组织工程研究

BACKGROUND: Taohong Siwu Decoction has a good effect in the treatment of periprosthetic infection after joint replacement, and can improve the function of joint movement. However, most present studies focus on the antibacterial effect of single drug and its components in the prescription, and there is little research on the compound and other mechanisms. OBJECTIVE: To explore the mechanism of Taohong Siwu Decoction in the treatment of periprosthetic joint infection. METHODS: Ingredients and target genes of Semen Persicae, Carthami Flos, Rehmanniae Radix Praeparata, Paeoniae Radix Alba, Angelicae Sinensis Radixand and Chuanxiong Rhizoma were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Periprosthetic joint infection-related target genes were obtained from the human gene database (GeneCards). Cytoscape3.7.2 was used for constructing a “Drug-Ingredient-Target-Disease” network. The key target genes were introduced into the STRING to construct protein-protein interaction network. We analyzed the mechanism by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology biological enrichment analysis. RESULTS AND CONCLUSION: (1) Totally 15 active components, such as quercetin, luteolin and kaempferol, were screened from Taohong Siwu Decoction, which acted on 34 key genes, such as vascular endothelial growth factor A, tumor necrosis factor, and interleukin-6. (2) Gene Ontology function enrichment showed that the biological process and function of Taohong Siwu Decoction were concentrated in positive regulation of biological process, response to chemical stimulus, response to stress, and regulation of apoptosis. (3) Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that the treatment of periprosthetic joint infection by Taohong Siwu Decoction mainly involved pathways in cancer, AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, inflammatory bowel disease and cytokine-cytokine receptor interaction pathway. (4) Through the study of network pharmacology, it is found that Taohong Siwu Decoction could treat periprosthetic joint infection by inhibiting bacterial growth and improving hemorheology, which provided a preliminary theoretical basis for the application of “activating circulation and removing blood stasis” in periprosthetic joint infection and a new idea for subsequent experiments.

A dosimetric study of half jaw technique applied in the treatment planning for oropharyngeal cancer patients / 中华放射医学与防护杂志

Objective To investigate the potential dosimetric advantages of half jaw volumetric modulated arc therapy ( H-VMAT) applied to the Oropharyngeal Cancer, comparing with full jaw VMAT (F-VMAT) and intensity modulated radiotherapy ( IMRT ). Methods Planning CT images of 10 oropharyngeal cancer patients were retrospectively chosen and transferred to Eclipse treatment planning system v. 11. 0 (Varian Medical Systems, Pala Alto, USA), based on which H-VMAT, W-VMAT, and IMRT plans were created. Two full arcs (360°) were adopted for VMAT planning, and the 7 beams were equally distributed for IMRT planning. The optimization constraints remained the same for the three kinds of plans. The dosimetric parameters such as D2 , D98 , D50 , HI, and CI were evaluated for PGTV, PCTV1, PCTV2, PGTVln, and PCTVln. In addition, the maximum dose (Dmax) and D1 cc(minimum dose received by 1cc) of the brainstem and spinal cord were analyzed respectively. The mean dose ( Dmean ) to the parotids, oral cave, larynx, and cervical normal tissues were also reviewed. The monitor units ( MU) for all treatment plans were recorded. Results Comparisons of the three planning techniques showed that H-VAMT improved the HI and CI of the targets (except PCTV2) significantly (HI: F =3. 959, 6. 764, 10. 581, 6. 770, 13. 040, P<0. 05;CI:F=6. 594, 4. 138, 0. 842, 4. 031, 5. 388, P<0. 05);reduced Dmax(F=4. 509, 20. 331, P<0. 05) and D1 cc for brainstem and spinal cord (F=27. 432, 26. 314, P<0. 05) significantly;reduced Dmean(F=4. 279, 29. 498, 19. 295, P<0. 05) to the normal tissues of the mouth, throat and neck significantly. The V50 of the mouth and throat were slightly lower in IMRT plans (F=8. 140, P<0. 05). IMRT was slightly better than W-VMAT in sparing oral cavity and larynx, but the dose distribution was the worst. The H-VMAT plans showed the best dose distribution in the cervical normal tissues, especially for the lower and posterior parts, where IMRT plans displayed high dose curves. Conclusions H-VMAT is dosimetrically superior than W-VMAT and IMRT for oropharyngeal cancer, which could be considered for clinical applications.