Search

BackgroundGallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient.Case presentationThe patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient’s blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay.ConclusionOlaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

Background The first-line chemotherapy regimen for advanced gallbladder cancer (GBC) is gemcitabine plus platinum (GP), despite its efficacy is limited. The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus oxaliplatin (GEMOX) as the first-line chemotherapy for unresectable locally advanced or metastatic GBC. Methods The data of patients with unresectable locally advanced or metastatic GBC, who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were retrieved. This retrospective study evaluated the clinical characteristics, survival outcomes and adverse events. Results A total of 44 patients (n=25 in mFOLFIRINOX, n=19 in GEMOX) were included. There were no significant differences between groups in baseline characteristics. The median progression free survival (mPFS) was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group [P=0.021; hazard ratio (HR), 0.499; 95% CI, 0.266 to 0.937]. The median overall survival (mOS) was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group (P=0.019; HR, 0.471; 95% CI, 0.239 to 0.929). Disease control rate (DCR) was 76.0% in the mFOLFIRINOX group and 47.4% in the GEMOX group (P=0.051). The rate of grade 3-4 adverse events was 48% in the mFOLFIRINOX group and 36.8% in the GEMOX group (P=0.459). The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group, while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group. Conclusions mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC, and the results need to be further verified by prospective clinical studies.

ObjectivesTo investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure.MethodsBased on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system.ResultsOf the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII>510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, PConclusionsSII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT04140552).

Background Gallbladder cancer (GBC) is the most common cancer type of the biliary tract, and an association has been found between chronic calculous cholecystitis (CCC) and an increased incidence of GBC mortality. An understanding of the relationship between CCC and its carcinogenesis may enable us to prevent and cure GBC. In this study, we attempted to explore changes in the microbiome profile that take place during the transition from chronic cholecystitis mucosa to malignant lesions. Results Seven paired human GBC and CCC samples were provided by patients who had undergone laparoscopic cholecystectomy or radical cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate changes in the microbiota between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and showed apparent differences in their biliary microbial composition and gene function. Peptostreptococcus stomatis and Enterococcus faecium may potentially play a role in GBC progression. In addition, the metagenomic species profiles, co‐abundance and co‐exclusion correlations, and CAZyme prevalence showed significant differences between the CCC and GBC groups. Conclusion Our data suggested that changes in the microbiota between CCC and GBC may help deepen our understanding of the complex spectrum of different microbiotas involved in the development of GBC. Although the cohort size was small, this study has presented the first evidence of the existence of an altered biliary microbiota in GBC, which is clearly different from that in CCC patients., 1. In the development of GBC, species richness and evenness are significantly increased compared with CCC group. 2. Abundance of NAD‐dependent protein deacetylase, deoxyribonuclease V, branched‐chain amino acid transport system permease protein and chorismate mutase were enriched in the GBC group. Archaeal S‐adenosylmethionine was enriched in the CCC group. 3. GHs, GTs, PLs and GEs were significantly higher in the CCC group, while GT77 was enriched in the GBC group.

Background: Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract, and chronic calculous cholecystitis (CCC) is associated with an increased risk of GBC mortality. Understanding the relationship between CCC and its carcinogenesis might enable us to prevent and cure GBC. In this study, we attempted to explore microbiome profile changes during the transition from chronic cholecystitis mucosae to malignant lesions. Methods: Seven paired human GBC and CCC samples were obtained from patients who underwent radical cholecystectomy or laparoscopic cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate the microbiota changes between the two groups. Findings: Seven paired human GBC and CCC samples were obtained from patients who underwent radical cholecystectomy or laparoscopic cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate the microbiota changes between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and apparent differences in their biliary microbial composition and gene function. Peptostreptococcus_stomatis and Enterococcus_faecium may have potentially role in GBC progression. In addition, metagenomic species profiles, co-abundance and co-exclusion correlations and CAZyme prevalence showed significant differences between the CCC and GBC groups. Interpretation: Our data suggest microbiota changes between CCC and GBC, which might help us deepen our understanding of the complex landscape of different microbiotas in the development of GBC. Funding Statement: This study was supported by the National Natural Science Foundation of China (31600075), Shanghai Key Laboratory of Biliary Tract Disease Research Foundation (17DZ2260200), the National Natural Science Foundation of China (No. 81572819, 81773043,91440203, 31601021), the Peak Plateau Discipline Construction Project of Shanghai Jiaotong University School of medicine (No. 20181808), the Program of Shanghai Academic Research Leader (No. 19XD1422700), the Shanghai Natural Science Foundation (No 17ZR1418500) and Shanghai Pujiang Program (No 17PJD025). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Xinhua Hospital affiliated with the Shanghai Jiao Tong University School of Medicine (No. XHEC-D-2019-049). All experiments were carried out in accordance with the approved guidelines. Informed consent was obtained from the patients.

To study the psychologic status and their influencing factors in congenital microtia patients and their families.Totally one hundred and two congenital microtia patients (79 men, 23 women, mean age 13.62 +/- 7.2 years) were enrolled. The patients and their families answered the questionnaire written by ourselves to identify the psychosocial problems.(1) 23.5% patients were found to have severe psychosocial problems, such as lack of self-confidence, close and fear and so on. (2) With the growth of age, psychosocial problems of the patients were rated high (P0.05). (3) For patients who found their deformations early, psychosocial problems also were rated low. (4) For patients who found their deformations by themselves, psychosocial problems also were rated low. (5) The education and psychosocial impact for parents all affected patients deeply.To prevent psychosocial problems, we should operate for patients as early as possible. And correct guidance is very important for youngsters.