The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis. METHODS: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort. PNI-related genomic and transcriptomic profiles were analyzed in MSK and ZS-ICC cohorts. GO, KEGG, and ssGSEA analyses were performed. Immunohistochemistry was used to investigate the relationship between PNI and markers of neurons, hydrolases, and immune cells. The efficacy of adjuvant therapy in ICC patients with PNI was also assessed. RESULTS: A total of 30.6% and 20.7% ICC patients had PNI in MSK and TMA cohorts respectively. Patients with PNI presented with malignant phenotypes such as high CA19-9, the large bile duct type, lymph node invasion, and shortened overall survival (OS) and relapse-free survival (RFS). Nerves involved in PNI positively express tyrosine hydroxylase (TH), a marker of sympathetic nerves. Patients with PNI showed high mutation frequency of KRAS and an immune suppressive metastasis prone niche of decreased NK cell, increased neutrophil, and elevated PD-L1, CD80, and CD86 expression. Patients with PNI had an extended OS after adjuvant therapy with TEGIO, GEMOX, or capecitabine. CONCLUSION: Our study deciphered the genomic features and the immune suppressive metastasis-prone niche in ICC with PNI. Patients with PNI showed a poor prognosis after surgery but a good response to adjuvant chemotherapy.

The LINC00261/MiR105-5p/SELL axis is involved in dysfunction of B cell and is associated with overall survival in hepatocellular carcinoma.

Background: Previous studies have been reported the immune dysfunction of various live tissues. However, the potential molecular mechanism of post-transcriptional regulation of immune related genes in hepatocellular carcinoma (HCC) is still not clear. We tried to identify crucial immune related biomarkers associated with HCC patients' outcomes and to reveal the transcriptional regulation. Method: The fractions of 22 immune cells in tumor and adjacent tissues were estimated by CIBERSORT. Kruskal-Wallis test and differentially expressed analyzes were used for comparative studies. Cox proportional hazard regression model, Kaplan-Meier estimates and Log-rank test were used for survival analyses. Results: From The Cancer Genome Atlas (TCGA), the gene, lncRNA and miRNA expression profiles of 379 HCC samples with clinical information were used for comparative studies. Eleven adaptive and innate immune cell types were significantly altered in HCC samples, including B cell memory, regulatory T cells and follicular helper T cells. Differentially expressed competing endogenous RNA (ceRNA) network associated with patients' overall survival was identified. Then, the novel pathway, including LINC00261, MiR105-5p and selectin L(SELL) was found and may be potential novel biomarkers for patients' outcomes and immunotherapy. Furthermore, SELL was significantly positively correlated (correlation coefficients: 0.47-0.69) with 12 known gene signatures of immunotherapy except for programmed cell death 1 (PDCD1). Conclusions: Our findings could provide insights into the selection of novel LINC00261/MiR105-5p/SELL pathway which is associated with overall survival and may impact on efficacy of immunotherapy in HCC.

Challenges in Cross-Cultural Communication in Breast Cancer Surgery: Is there a Gender Gap?

The aim of this study is to identify [1] facilitators and barriers to cross-cultural communication with Canadian immigrants during the breast cancer (BC) surgical consultation and [2] the impact of cultural sensitivity training on the perception of cross-cultural communication barriers. A 29-item questionnaire mailed to 450 surgeons was developed based on the Ottawa Decision Support Framework, informed by interviews with BC practitioners and a literature review. The inclusion criteria are English-speaking general surgeons practicing in Vancouver, Montréal, and Toronto, home to > 60% of Canada's immigrant population. The association between surgeon characteristics and barriers to communication was assessed using the chi-square or Fisher's exact test. Univariate and multivariable logistic regression models estimated odds ratios and 95% confidence intervals for the association between frequent perception of each barrier to communication and gender, career stage, and percentage of foreign-born patients. Between June and September 2017, 130 surveys were returned for a 29% response rate. The majority of practitioners reported experiencing language barriers in consultation with immigrant patients (71.4%). In the patient-provider relationship, the most commonly reported barrier was the patient's lack of medical understanding (81.4%). At the system level, the absence of a relative for translation was the most frequently encountered challenge (77.1%). On multivariable analysis adjusting for career stage and percentage of foreign-born patients, female gender of a surgeon was associated with more frequent perception of barriers related to language (OR 4.91, [95% CI 1.43, 16.82; p = 0.0114]), the patient's desired role in decision-making (OR 3.000 [95% CI 1.116-8.059; p = 0.0294]), and poor access to interpreters (OR 3.63 [95% CI 1.24, 10.64; p = 0.0189]). Furthermore, on multivariable analysis adjusting for gender and career stage, surgeons identified as having < 25% foreign-born patients in their practice were less likely to identify communication barriers due to the patients' perception and understanding of their healthcare (OR 0.32 [95% CI 0.11, 0.95; p = 0.041]). Cultural sensitivity training did not appear to be an influential factor though this may be due to the low number of surgeons who received training (5.7%). There are multiple cross-cultural communication challenges. Gender, years in practice, and the cultural diversity of a practice might play significant roles in the identification and perception of these barriers.

Cambridge experience in spontaneous bone regeneration after traumatic segmental bone defect: a case series and review of literature.

High-energy traumatic long bone defects are some of the most challenging to reconstruct. Although cases of spontaneous bone regeneration in these defects have been reported, we are aware of no management guidelines or recommendations for when spontaneous bone regeneration should be considered a viable management option. We aim to identify how certain patient characteristics and surgical factors may help predict spontaneous bone regeneration. A total of 26 cases with traumatic segmental defects were treated at our institution, with eight cases (30.8%) undergoing spontaneous regeneration. We discuss four in detail. Six (75%) reported a degree of periosteal preservation, four (50%) were associated with traumatic brain injury and none were complicated by infection. The average time to spontaneous bone regeneration was 2.06 months. According to our cases, patients with favourable characteristics may benefit from delaying surgical treatment by 6 weeks to monitor for any signs of spontaneous bone formation.

Comparing Observation, Axillary Radiotherapy, and Completion Axillary Lymph Node Dissection for Management of Axilla in Breast Cancer in Patients with Positive Sentinel Nodes: A Systematic Review.

PURPOSE: Several randomized controlled trials (RCTs) have investigated observation or axillary radiotherapy (ART) in place of completion axillary lymph node dissection (cALND) for management of positive sentinel nodes (SNs) in clinically node-negative women with breast cancer. The optimal treatment strategy for this population is not known. METHODS: MEDLINE, Embase, and EBM Reviews-NHS Economic Evaluation Database were searched from inception until July 2019. A systematic review and narrative summary was performed of RCTs comparing observation or ART versus cALND in clinically node-negative female breast cancer patients with positive SNs. The Cochrane risk of bias tool for RCTs was used to assess risk of bias. Outcomes of interest included overall survival (OS), disease-free survival (DFS), axillary recurrence, and axillary surgery-related morbidity. RESULTS: Three trials compared observation with cALND, and two trials compared ART with cALND. No studies blinded participants or personnel, and there was heterogeneity in inclusion criteria, study design, and follow-up. Neither observation nor ART resulted in statistically inferior 5- or 8-year OS or DFS compared with cALND. There was also no statistically significant increase in axillary recurrences associated with either approach. Four trials reported morbidity outcomes, and all showed cALND was associated with significantly more lymphedema, paresthesia, and shoulder dysfunction compared with observation or ART. CONCLUSIONS: Women with clinically node-negative breast cancer and positive SNs can safely be managed without cALND.

Rotating-hinge knee prosthesis as a viable option in primary surgery: Literature review & meta-analysis.

BACKGROUND: Rotating-hinge knee replacements are usually reserved for revision surgeries, when the extent of soft tissue loss makes a constrained implant more suitable. They remain an uncommon choice in primary surgery when the soft tissue loss is not as extensive. METHODS: We completed a systematic review and meta-analysis to assess patients who underwent a Total Knee Replacement (TKR) with the rotating-hinge prosthesis in the primary setting. We searched PubMed and Embase for articles published in the ten years prior June 2017: Prosthesis survival rates, causes of failure, and clinical/functional scores were the primary outcomes. Twenty-one articles met the inclusion criteria for meta-analysis. Articles were grouped into (1) non-tumour (n=11) and (2) tumour indications (n=10). Survival data was summarized in forest plots, generated using Stata. RESULTS: We found that for certain indications the prosthesis has impressive survival rates and functional outcomes. Short-term (1-5 year) prosthesis survival in non-tumour cases was 92% (95% CI, 87-98%) and 77% (95% CI, 68-87%) in tumour cases. Mid-term (6-10 year) survival was 82% (95% CI, 74-89%) and 69% (95% CI, 57-81%) in non-tumour and tumour studies respectively. In analysis of clinical scores, patients showed a significant improvement in their pain score. Infection was the most commonly cited cause of prosthesis failure in both non-tumour and tumour studies, attributing to 31.5% and 37.6% of failures respectively. Aseptic loosening, dislocation and fracture were also commonly cited complications. CONCLUSION: We concluded that the rotating-hinge knee prosthesis is a viable option in primary surgery when there is extensive soft tissue destruction surrounding the joint. LEVEL OF EVIDENCE: I.