Patients who complete neoadjuvant chemotherapy for breast cancer without a pathological complete response have a high risk of relapse. A randomized trial comparing capecitabine with no additional ...adjuvant therapy showed that capecitabine prolonged disease-free and overall survival.
Patients who have residual invasive breast cancer after the receipt of neoadjuvant chemotherapy have a high risk of relapse.
1
The rate of complete response as assessed on pathological testing (hereafter, pathological complete response) ranges from 13 to 22% among patients with human epidermal growth factor receptor 2 (HER2)–negative primary breast cancer.
1
Patients who do not have a pathological complete response after the receipt of neoadjuvant taxane and anthracycline chemotherapy have a 20 to 30% risk of relapse.
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Patients with HER2-negative cancer who receive neoadjuvant chemotherapy often receive postoperative radiation therapy, whereas endocrine therapy is administered to patients with hormone-receptor–positive disease . . .
Abstract
Background
We compared the surgical outcomes of single-incision laparoscopic surgery (SILS) and conventional laparoscopic surgery (CLS) for gastric gastrointestinal stromal tumor (GIST).
...Methods
We performed single-incision gastric wedge resection on prospectively-enrolled 15 consecutive patients with gastric GIST between November 2020 and April 2022 in a single tertiary center. The early perioperative outcomes of these patients were compared to those of patients who underwent CLS. The indications did not differ from those for conventional laparoscopic procedures for gastric GIST.
Results
In total, 30 patients were assigned to the SILS (n = 15) and CLS (n = 15) groups. There were no significant differences in the estimated blood loss and intraoperative blood transfusion between the SILS and CLS groups. There were no intraoperative complications or conversions to multiple-port or open surgery in the SILS group. Proximally located tumors were more commonly treated with CLS than with SILS (
P
= 0.045). GISTs located in the greater curvature were more commonly treated with SILS than with CLS, although the difference was not statistically significant (
P
= 0.08). The mean incision length in the SILS group was 4.1 cm shorter than that in the CLS group (3.2 ± 0.7 and 7.3 ± 5.2 cm, respectively,
P
= 0.01). The postoperative analgesic dose was significantly lower in the SILS than in the CLS group (0.4 ± 1.4 and 2.1 ± 2.3, respectively
P
= 0.01). Also, the duration of postoperative use of analgesic was shorter in SILS than in CLS (0.4 ± 0.7 and 2.0 ± 1.8, respectively,
P
= 0.01). There were no significant differences in the early postoperative complications between the groups.
Conclusions
SILS is as safe, feasible, and effective for the treatment of gastric GIST as CLS with comparable postoperative complications, pain, and cosmesis. Moreover, SILS can be considered without being affected by the type or location of the tumor.
Extraction of cell-free DNA (cfDNA), which exists at an extremely low concentration in plasma, is a critical process for either targeted-sensing or massive sequencing of DNAs. However, such small ...amount of DNA cannot be fully obtained without high-speed centrifugation (<20,000 g). Here, we developed a centrifugation-free cfDNA extraction method and system that utilizes an immiscible solvent under single low vacuum pressure throughout the entire process. It has been named Pressure and Immiscibility-Based EXtraction (PIBEX). The amounts of extracted cfDNA by PIBEX were compared with those extracted by the conventional gold standards such as QIAGEN using quantitative PCR (qPCR). The PIBEX system showed equal performance regarding extraction amount and efficiency compared to the existing method. Because the PIBEX eliminates the troublous and repetitive centrifugation processes in DNA extraction, it can be further utilized in microfluidic-sample preparation systems for circulating nucleic acids, which would lead to an integrated sample-to-answer system in liquid biopsies.
Gastric cancer has been categorized into molecular subtypes including Epstein-Barr virus (EBV)-positive tumors, which provide clinicopathological and prognostic information. In this study, we ...investigated the EBV infection status of patients with gastric cancer and its correlation with the clinicopathological characteristics and multiple genes related to gastric carcinogenesis. The data of 460 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection between January 2017 and February 2022 were analyzed. The clinicopathological features and prognosis of the patients with EBV-positive gastric cancers were compared with those of EBV-negative gastric cancers. Immunohistochemistry for epidermal growth factor receptor (EGFR), C-erb B2, Ki-67, and p53 was performed. Additionally, in situ hybridization was conducted to detect EBV, and microsatellite instability (MSI) analysis was used to assess the deficiency in mismatch repair (MMR) genes. EBV-positivity and MSI were identified in 10.4% and 37.3% of gastric cancer patients, respectively. EBV positivity was associated with male gender (P = 0.001), proximal location (P = 0.004), poorly differentiated histological type (P = 0.048), moderate to severe lymphoid stroma (P = 0.006), high Ki-67 expression (P = 0.02), and a shorter resection margin. EGFR was more often expressed in EBV-negative gastric cancers (P < 0.001). MSI tumors were associated with older age (P = 0.01), the presence of lymphatic invasion (P = 0.02), less perineural invasion (P = 0.05), and the presence of H. pylori infection (P = 0.05). EBV positive gastric cancer is associated with increased Ki-67 and decreased EGFR expression and a shorter resection margin due to the prominent lymphoid stroma. However, MMR deficiency is not associated with EBV status even though MSI gastric cancer is related to H. pylori status.
Obesity is a risk factor for various types of cancer. Leptin, an adipocyte-derived hormone, may stimulate the proliferation of gastric cancer cells. However, the effect of leptin and underlying ...mechanism in gastric cancer remain unclear. In the present study, the role of leptin in gastric cancer was evaluated. The effect of leptin on the JAK-STAT and MEK signaling pathways was investigated in gastric cancer cells using wound-healing and cell invasion assays, immunoblotting and inhibition studies. Cancer-initiating cells derived from gastric cancer cells were used to investigate the effect of leptin on the maintenance of stemness and epithelial-mesenchymal transition (EMT) by immunoblotting. Clinicopathological characteristics including the serum leptin level and overall survival (OS) were analyzed in patients with (n=23) and without (n=23) obesity. Leptin induced the migration and invasion of gastric cancer cells by activating AKT and ERK and upregulating vascular endothelial growth factor (VEGF). Leptin increased the mRNA and protein levels of markers of stemness (CD44) and the EMT (Snail and N-cadherin). Pharmacological inhibitors of the JAK-STAT and MEK signaling pathways decreased leptin-induced migration and invasion, and the expression of VEGF. Obesity was associated with an elevated leptin level and body mass index was positively correlated with the leptin level (P=0.001 for both). The 5-year OS rate was not significantly different between the two groups (P=0.098). Leptin stimulates the migration and invasion of gastric cancer cells by activating the JAK-STAT and MEK pathways, and contributes to the maintenance of cancer stemness and metastatic potential. The present findings support an adverse effect of obesity in gastric cancer. Consequently, targeting of leptin-associated signaling pathways may have therapeutic potential for gastric cancer.
Prostate cancer (PCa) is the most commonly diagnosed malignancy among men in developed countries. The five-year survival rate for men diagnosed with early-stage PCa is approximately 100%, while it is ...less than 30% for castration-resistant PCa (CRPC). Currently, the detection of prostate-specific antigens as biomarkers for the prognosis of CRPC is criticized because of its low accuracy, high invasiveness, and high false-positive rate. Therefore, it is important to identify new biomarkers for prediction of CRPC progression. Extracellular vesicles (EVs) derived from tumors have been highlighted as potential markers for cancer diagnosis and prognosis. Specifically, urinary EVs directly reflect changes in the pathophysiological conditions of the urogenital system because it is exposed to prostatic secretions. Thus, detecting biomarkers in urinary EVs provides a promising approach for performing an accurate and non-invasive liquid biopsy for CPRC. In this study, we effectively isolated urinary EVs with low protein impurities using size-exclusion chromatography combined with ultrafiltration. After EV isolation and characterization, we evaluated the miRNAs in urinary EVs from healthy donors and patients with CRPC. The results indicated that miRNAs (miR-21-5p, miR-574-3p, and miR-6880-5p) could be used as potential biomarkers for the prognosis of CRPC. This analysis of urinary EVs contributes to the fast and convenient prognosis of diseases, including CRPC, in the clinical setting.
BACKGROUNDThere are increasing concerns about that sentinel lymph node biopsy (SLNB) could be omitted in patients with clinically T1-2 N0 breast cancers who has negative axillary ultrasound (AUS). ...This study aims to assess the false negative result (FNR) of AUS, the rate of high nodal burden (HNB) in clinically T1-2 N0 breast cancer patients, and the diagnostic performance of breast magnetic resonance imaging (MRI) and nomogram. METHODSWe identified 948 consecutive patients with clinically T1-2 N0 cancers who had negative AUS, subsequent MRI, and breast conserving therapy between 2013 and 2020 from two tertiary medical centers. Patients from two centers were assigned to development and validation sets, respectively. Among 948 patients, 402 (mean age ± standard deviation, 57.61 ± 11.58) were within development cohort and 546 (54.43 ± 10.02) within validation cohort. Using logistic regression analyses, clinical-imaging factors associated with lymph node (LN) metastasis were analyzed in the development set from which nomogram was created. The performance of MRI and nomogram was assessed. HNB was defined as ≥ 3 positive LNs. RESULTSThe FNR of AUS was 20.1% (81 of 402) and 19.2% (105 of 546) and the rates of HNB were 1.2% (5/402) and 2.2% (12/546), respectively. Clinical and imaging features associated with LN metastasis were progesterone receptor positivity, outer tumor location on mammography, breast imaging reporting and data system category 5 assessment of cancer on ultrasound, and positive axilla on MRI. In validation cohorts, the positive predictive value (PPV) and negative predictive value (NPV) of MRI and clinical-imaging nomogram was 58.5% and 86.5%, and 56.0% and 82.0%, respectively. CONCLUSIONThe FNR of AUS was approximately 20% but the rate of HNB was low. The diagnostic performance of MRI was not satisfactory with low PPV but MRI had merit in reaffirming negative AUS with high NPV. Patients who had low probability scores from our clinical-imaging nomogram might be possible candidates for the omission of SLNB.
The human epidermal growth factor receptor 2 (HER2)-positive breast cancer with overexpression of HER2 accounts for approximately 25% of breast cancers and is more aggressive than other types of ...breast cancer. Lapatinib has been widely used as a HER2-targeted therapy, however, a number of patients develop lapatinib resistance and still suffer from poor prognosis. Therefore, it is essential to identify novel therapeutic targets that could overcome lapatinib resistance. In this study, we carried out phosphoproteomic analysis of lapatinib sensitive and resistant cell lines (SKBR3 and SKBR3-LR) using stable isotope labeling with amino acids in cell culture (SILAC). We identified 3808 phosphopeptides from 1807 proteins and then analyzed signaling pathways, Gene Ontology, and protein-protein interaction networks. Finally, we identified PAK2 as a therapeutic target from the network analysis and validated that PAK2 knockdown and PAK inhibitor treatment resensitize the lapatinib resistant cells to lapatinib. This results suggest that PAK2 is a potent therapeutic target to overcome acquired lapatinib resistance in HER2-positive breast cancer cells.
•Phosphoproteomic analysis identified PAK2 as a drug target for lapatinib resistance.•PAK2 knockdown restores lapatinib sensitivity of lapatinib-resistant SKBR-LR cells.•Cotreatment of lapatinib with PAK inhibitor restores the sensitivity to lapatinib.
Adjuvant chemotherapy (AC) after curative gastrectomy is the standard treatment for patients with locally advanced gastric adenocarcinoma in East Asia; however, for various reasons, some patients do ...not receive this treatment. The aim of this study was to develop a system that reflects the survival rate of patients who do not receive AC.
A modified tumor-node-metastasis (TNM) staging system was developed based on the overall survival (OS) of gastric cancer patients after curative gastrectomy without AC at Seoul St. Mary's hospital. A survival prediction model was developed based on the modified staging system and risk factors for OS, which were examined using the Cox proportional hazards regression model. The model was internally validated for the power of prediction and discrimination, compared with the American Joint Committee on Cancer (AJCC) Cancer Staging Manual 8th edition; it was externally validated using data from two other tertiary teaching hospitals.
Of the 185 patients in the development set, the 5-year OS rates for modified stages IIA, IIB, IIC, IIIA, and IIIB were 80.2%, 74.0%, 56.7%, 50.0%, and 25.0%, respectively; the median OS intervals for modified stages IIIC and IIID were 21.0 and 11.0 months, respectively. Age, American Society of Anesthesiologists physical status, and postoperative complications were significantly associated with OS. The concordance index (0.768 vs. 0.686), Akaike Information Criterion (745.88 vs. 794.84), and estimated area under the curve (0.7567 vs. 0.6655) were all superior for the prediction model, compared with the AJCC TNM stage. For the validation set of 157 patients, the model performed better for the prediction and discrimination of OS.
The newly developed survival prediction model improves the accuracy of OS prediction for stage II and III gastric cancer patients without AC after curative gastrectomy.
•ASurvival prediction through AJCC 8th edition can be inaccurate in gastric cancer patients without adjuvant chemotherapy.•We developed a survival prediction model for patients with stage-II or -III gastric cancer without adjuvant chemotherapy.•The model will assist clinicians and patients with decisions regarding treatment planningwithout adjuvant chemotherapy.
IntroductionSymptoms due to chemotherapy are common in patients with cancer. Cancer-related symptoms are closely associated with the deterioration of physical function which can be associated with ...decreased quality of life and increased mortality. Thus, timely symptom identification is critical for improving cancer prognosis and survival. Recently, remote symptom monitoring system using digital technology has demonstrated its effects on symptom control or survival. However, few studies examined whether remote monitoring would contribute to retaining physical function among patients with cancer. Therefore, this study aimed to evaluate the effectiveness of mobile-based symptom monitoring in improving physical function among patients with cancer under chemotherapy.Methods and analysisThis study is a multicentre, open-label, parallel-group, randomised controlled trial. We will recruit 372 patients at three tertiary hospitals located in Seoul, South Korea. Study participants will be randomly assigned to either an intervention group receiving the ePRO-CTCAE app and a control group receiving routine clinical practice only. The primary outcome is changes in physical function from commencement to completion of planned chemotherapy. A linear mixed model will be performed under the intention-to-treat principle. The secondary outcomes include physical activity level; changes in pain interference; changes in depressive symptom; unplanned clinical visits; additional medical expenditure for symptom management; completion rate of planned chemotherapy; changes in symptom burden and health-related quality of life; and 1-year overall mortality.Ethics and disseminationThe study has been approved by the institutional review board and ethics committee at the three university hospitals involved in this trial. Written informed consent will be obtained from all the participants. The results of the trial will be submitted for publication in peer-reviewed academic journals and disseminated through relevant literatures.Trial registration numberKCT0007220.
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