Delphian lymph node metastasis predicts occult contralateral carcinoma for unilateral papillary thyroid carcinoma patients with contralateral benign nodules.

BACKGROUND: For unilateral PTC patients with benign nodules in the contralateral lobe evaluated preoperatively, the necessity of total thyroidectomy remains controversial. This study aimed to investigate the predictive factors for occult contralateral carcinoma and whether DLN metastasis could predict it. METHODS: A total of 148 patients with unilateral PTC and contralateral benign nodules who were treated with a near-total thyroidectomy or TT at a single institution between August 2018 and April 2020 were enrolled. Clinicopathological features such as age, sex, TgAb or TPOAb level, primary tumor location, nodule number in contralateral lobe, carcinoma number in primary lobe, tumor size, capsular invasion, central lymph node metastasis, DLN metastasis were analyzed to investigate the rate and predictive factors of occult contralateral carcinoma. RESULTS: 44.6% patients were diagnosed with occult contralateral thyroid carcinoma. Univariate analysis showed that sex (P = 0.008), mulifocality of primary carcinoma (P < 0.001), tumor size (P = 0.033), capsular invasion (P = 0.042), CLN metastasis (P = 0.004), DLN metastasis (P = 0.001) were associated with occult contralateral carcinoma. Multivariate analysis showed that multifocality of primary carcinoma (p = 0.000, OR = 9.729), DLN metastasis (p = 0.042, OR = 4.701), capsular invasion (p = 0.022, OR = 2.909), and male patients (p = 0.006, OR = 3.926) were all independent predictive factors. CONCLUSION: For unilateral PTC patients with benign nodules in the contralateral lobe evaluated preoperatively, multifocality of primary carcinoma, DLN metastasis, capsular invasion, and male patients are independent predictors of occult contralateral carcinoma. We suggest separate excision and frozen section of DLN intraoperatively, if DLNs were confirmed metastasized, a TT was highly recommended.

HER2-positive metastatic breast cancer with brain metastases responds favorably to pyrotinib and trastuzumab-based treatment: A case report and literature review.

For HER2-positive metastatic breast cancer patients with the brain involved at initial diagnosis, there was no standard regimen before 2022 when the HER2CLIMB trial published its final overall survival analysis, and the prognosis is relatively poor under the current treatment strategy. We herein reported a case of a female patient who was initially diagnosed with HER2-positive metastatic breast cancer with brain metastases, receiving pyrotinib and trastuzumab-based systematic therapy after palliative craniocerebral radiotherapy as the first-line systematic therapy. During the treatment, the tumor lesions showed obvious regression, and chemotherapy drugs were gradually removed from the regimen. The patient continued receiving trastuzumab and pyrotinib for HER2-targeted therapy. She had achieved more than 26 months of progression-free survival and the disease was stable during the evaluation in April 2022. Radiotherapy followed by dual HER2-targeted therapy of macromolecular monoclonal antibodies trastuzumab and micromolecular TKI pyrotinib plus chemotherapy could be an alternative option for this subtype of patients and need to be further verified by future clinical trials.

Prophylactic Central Neck Dissection for cN1b Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: The value of prophylactic central neck dissection (PCND) for papillary thyroid carcinoma (PTC) with clinically evident lateral cervical lymph node metastases (cN1b) remains unclear. Therefore, a systematic review and meta-analysis was conducted to assess the efficacy and safety of PCND. METHODS: A comprehensive systematic search was conducted on PubMed, Web of Science, Cochrane library and Embase databases up to September 2021 to identify eligible studies. Controlled clinical trials assessing therapeutic effects and safety of PCND for cN1b PTC patients were included. The risk of bias for each cohort study was assessed using the Newcastle-Ottawa Scale (NOS). The primary outcomes were indexes related to the locoregional recurrence (LRR) and surgical complications. Review Manager software V5.4.0 was used for statistical analysis. A fixed effects model was adopted for the data without heterogeneity, otherwise a random effects model was used. RESULTS: We included 4 retrospective cohort studies, which comprised 483 PTC patients. There was no statistically significant difference in the central neck recurrence (CNR) (10.2% vs. 3.8%, relative risk (RR) = 1.82; 95%CI 0.90-3.67; P = 0.09), lateral neck recurrence (LNR) (5.1% vs. 7.7%, RR = 0.47; 95% CI 0.13-1.74; P = 0.26), and overall recurrence (OR) (18.9% vs. 16.9%, RR = 0.77; 95%CI 0.34-1.76; P = 0.54), between LND + PCND group and LND group. Simultaneously, PCND increased the risk of permanent hypoparathyroidism (11.4% vs. 4.5%, RR = 2.70, 95%CI 1.05-6.94; P = 0.04) and overall complications (17.0% vs. 5.3%, RR = 3.28; 95%CI 1.37-7.86; P = 0.008). CONCLUSIONS: This meta-analysis showed that PCND did not have any advantage in preventing LRR for cN1b PTC. Meanwhile, PCND may result in the increased rate of surgical complications. However, the current evidence is limited and more clinical trials are still needed to further clarify the true role of PCND. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, CRD42021281825.

Retroperitoneal metastasis synchronous with brain and mediastinal lymph nodes metastasis from breast invasive ductal carcinoma as the first site of distant metastasis: a case report and review of literature.

Breast carcinoma retroperitoneal metastasis is rare. The clinical symptoms of this disease are always non-specific. Laboratory tests are not always helpful for diagnosis and evaluation. We reported a case of a 52 year old Chinese patient who was diagnosed with retroperitoneal metastasis from breast invasive ductal carcinoma as the first site of distant metastasis synchronous with brain and mediastinal lymph nodes metastasis 4 years after modified radical mastectomy. Second-line chemotherapy of docetaxel and capecitabine was recommended. The response evaluation every two to three months was good. Unfortunately, the metastasis in the brain advanced. The patient was transferred to a radiotherapy department to receive radiotherapy and died 10 months later. We also review the related literature.

Increased Expression of Exosomal AGAP2-AS1 (AGAP2 Antisense RNA 1) In Breast Cancer Cells Inhibits Trastuzumab-Induced Cell Cytotoxicity.

BACKGROUND Trastuzumab therapy is important for patients with HER2-positive breast cancer, but more and more patients have experienced trastuzumab resistance during recent years. Accumulating evidence from recent studies showed that long non-coding RNAs (lncRNAs) play essential roles in chemoresistance of various cancer types, but the precise role of lncRNAs in trastuzumab resistance is unclear. In the present study, we aimed to identify the biofunction of lncRNA APAP2-AS1 in tranastuzumab resistance and to reveal the underlying regulatory mechanism. MATERIAL AND METHODS By culturing HER2-positive SKBR-3 and BT474 cells with transtuzumab-containing medium, we built trastuzumab-resistant cells. Quantitative real-time PCR was used to test the expression of AGAP2-AS1 in the built trastuzumab-resistant cells. Cell viability assay and TUNEL assay were used to test the cell viability and apoptosis in each group. Exosomes were purified from cells cultured in exosomes-depleted FBS and identified by transmission electron microscopy. RESULTS qRT-PCR assay suggested that AGAP2-AS1 was upregulated in the built trastuzumab-resistant cells when compared with parental sensitive cells. Cell viability assay showed that silencing of AGAP2-AS1 enhanced the cytotoxicity induced by trastuzumab treatment. Mechanistically, we revealed that AGAP2-AS1 was secreted outside cells by incorporation into exosomes in an hnRNPA2B1-dependent manner. More importantly, co-culture AGAP2-AS1-containing exosomes with sensitive cells reduced the trastuzumab-induced cell death, and silencing of AGAP2-AS1 from exosomes reversed this effect. In summary, AGAP2-AS1 promotes trastuzumab resistance of breast cancer cells through packaging into exosomes. CONCLUSIONS Knockdown of AGAP2-AS1 may be helpful for improving the clinical outcome for HER2+ breast cancer patients and could serve as a therapeutic target.