Impact of Neoadjuvant Chemotherapy (NAC) on Biomarker Expression in Breast Cancer.

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02-0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86-182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.

A Case of Esophageal MALT Lymphoma Mimicking a Subepithelial Tumor.

Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is a low-grade B-cell lymphoma that can develop in the mucosal layer of various organs, including the gastrointestinal tract, salivary glands, lungs, and skin. The most common site is the gastrointestinal tract, particularly the stomach. On the other hand, primary esophageal lymphomas are extremely rare. MALT lymphomas can undergo histological transformation into more aggressive B-cell lymphomas, such as diffuse large B-cell lymphoma, resulting in a poor prognosis. This paper reports a rare case of primary esophageal MALT lymphoma mimicking a subepithelial tumor located in the lower esophagus that was treated successfully with radiotherapy. MALT lymphoma should be included in a differential diagnosis when subepithelial tumors are found in the esophagus, particularly if endoscopic ultrasonography reveals the tumor to be located in the deep mucosal and submucosal layers. Following the precise diagnosis, accurate staging and appropriate treatment are crucial. Regular follow-up is necessary to assess the possibility of recurrence or transformation to high-grade lymphoma.

Tumor budding as a predictor of disease-free survival in patients with cholangiocarcinoma.

Background: Tumor budding is considered a prognostic factor in several solid cancer types. However, we lack comprehensive information on the importance of tumor budding in cholangiocarcinoma. Therefore, we aimed to assess the prognostic value of tumor budding in intrahepatic and extrahepatic cholangiocarcinomas and to evaluate its correlations with other clinicopathological parameters. Methods: We monitored 219 patients who underwent surgery for intrahepatic or extrahepatic cholangiocarcinoma at the Pusan National University Hospital between 2012 and 2021. Tumor budding was evaluated using the International Tumor Budding Consensus Conference scoring system. Tumor budding was classified into low (0-4), intermediate (5-9), and high (≥10). For statistical analysis, tumor budding was divided into two groups based on the cut-off value of 10 (lower: 0-9 vs. higher: ≥10). The correlations between clinicopathological parameters were examined using the chi-square and Fisher's exact test. The prognostic values of the variables were analyzed using the log-rank test and Cox regression analysis. Results: Low, intermediate, and high tumor buddings were identified in 135 (61.6%), 63 (28.8), and 21 (9.6%), patients, respectively. Higher tumor budding was related to the presence of lymphatic invasion (p = 0.017), higher tumor grade (p = 0.001), higher N category (p = 0.034). In the univariable and multivariable analyses, higher tumor budding was associated with shorter disease-free survival in 97 (44.3%) patients who underwent R0 resection (p < 0.001 and p = 0.011). Tumor budding did not significantly correlate with disease-specific survival in entire patients. Conclusion: Tumor budding may serve as a prognostic factor for intrahepatic and extrahepatic cholangiocarcinomas treated with R0 resection.

Laparoscopic gastric wedge resection and spleen-preserving distal pancreatectomy performed on a 6-cm gastric desmoid tumour with pancreatic invasion.

Desmoid tumours are rare tumours originating from fibroblasts, and are characterised by local infiltration and no metastasis. When complete resection is possible, surgical resection is considered a first-line treatment. In the case of large desmoid tumours, it is mainly performed by laparotomy, not laparoscopy. We report a case of a 43-year-old female patient presenting with a hypodense mass of approximately 5 cm in the posterior wall of the gastric antrum on computed tomography. There was no history of familial adenomatous polyposis, trauma or abdominal surgery. The patient underwent laparoscopic gastric wedge resection and spleen-preserving distal pancreatectomy without peri-operative complications. Pathological analysis revealed a desmoid tumour, which originated from the stomach and invaded the pancreas. Despite the large size and the locally infiltrative characteristics of these tumours, laparoscopic surgery can be an optimal treatment option due to its advantages.

[Paneth Cell Carcinoma of the Stomach].

Paneth cell carcinoma is a rare carcinoma composed predominantly or purely of malignant Paneth cells. An 83-year-old woman presented for evaluation of an elevated lesion in the stomach. On endoscopy, a 15 mm, discolored, elevated lesion with a central depression was found on the greater curvature of the gastric lower body. Endoscopic forceps biopsy revealed chronic gastritis with intestinal metaplasia. Magnifying endoscopy revealed an irregularly oval/tubular microsurface pattern and an irregular loop microvascular pattern with a demarcation line, suggestive of early gastric cancer. Therefore, endoscopic submucosal dissection was performed. Histopathological examination revealed a well-differentiated tubular adenocarcinoma limited to the muscularis mucosae and the tumor cells contained coarse eosinophilic granules in the cytoplasm. These tumor cells were diffusely and strongly stained for lysozyme, confirming the tumor diagnosis as Paneth cell carcinoma. Herein, we report a rare case of Paneth cell carcinoma and its endoscopic and histopathologic findings.

Lymphocyte-activating gene-3 expression is associated with tumor-infiltrating lymphocyte levels in HER2-positive breast cancers.

ABSTRACT: Lymphocyte-activating gene-3 (LAG-3, CD223) is the third inhibitory receptor targeted for immunotherapy. Several clinical trials investigating the use of interventions targeting LAG-3 are underway. The exact signaling mechanism downstream of LAG-3 is largely unknown, especially in breast cancer. The prognostic significance of tumor-infiltrating lymphocytes (TILs) in breast cancer has been previously determined.Among 167 human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, 90 and 78 patients were positive and negative for the hormone receptor, respectively. LAG-3 mRNA and protein expression levels in TILs were evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry, respectively, among 12 and 167 HER2-positive breast cancer samples, respectively.High expression of LAG-3 in TILs was significantly correlated with high levels of TILs (P = .003) and an abundance of tertiary lymphoid structures around invasive components (P = .014). In addition, high expression of LAG3 was significantly associated with positivity for programmed death-ligand 1 (PD-L1) in tumor cells, a high immunostaining score of PD-L1 in TILs, and a high total immunostaining score for PD-L1 in tumor cells and TILs (all, P < .001). High expression levels of LAG-3 mRNA were associated with high levels of TILs (P = .091).LAG-3 protein expression was not a prognostic factor in HER2-positive breast cancers, and LAG-3 expression in TILs was significantly associated with the levels of TILs in HER2-positive breast cancer, although it was not a prognostic factor.

Accelerated decomposition of Bi2S3 nanorods in water under an electron beam: a liquid phase transmission electron microscopy study.

Evaluating the stability of semiconductor photocatalysts is critical in the development of efficient catalysts. The morphological and microstructural behaviors of nanorod-shaped Bi2S3 semiconductors in aqueous solution were studied using a liquid cell transmission electron microscopy (TEM) technique. The rapid decomposition of Bi2S3 in water was observed under electron beam irradiation during TEM. Rounded bright spots due to a reduction in thickness were observed on the Bi2S3 nanorods at the initial stage of the decomposition, and rounded dark particles appeared outside of the nanorods in the solution, continuing the decomposition. This was confirmed by analyzing the atomic structure of the newly formed small particles, which consisted of an orthorhombic Bi2S3 phase. The stability-related decomposition of the Bi2S3 nanorods was demonstrated by considering the reduction and oxidation potentials of Bi2S3 in an aqueous solution. The effect of water radiolysis by the incident electron during TEM observations on the decomposition process was also determined by considering the time-dependent concentration behavior of the chemical species. Our study therefore reflects a novel route to evaluate the stabilities of semiconductor photocatalysts, which could ultimately solve a range of energy and environmental pollution problems.

The Diagnostic Accuracy and Postoperative Outcomes of Cervical Cancer Patients for MR-invisible or MR-visible Diagnosis of Combined T2- and Diffusion-weighted 3T MRI Using the External Phased-array Receiver.

BACKGROUND/AIM: This study aimed to determine the diagnostic accuracy and postoperative outcomes of early-stage cervical cancer patients [2009 FIGO stages IA2-IB1 (<2 cm)] diagnosed with magnetic resonance (MR)-invisible disease or MR-visible disease using the external phased-array receiver. PATIENTS AND METHODS: Between 2007 and 2014, 110 patients with a FIGO clinical stage IA2-IB1 (<2 cm) cervical cancer underwent primary surgical treatment after external array coil T2W and DW MR imaging following the diagnostic biopsy procedure. RESULTS: The median histological size of MR-invisible vs. MR-visible diagnosis was 3±6.4 mm and 16±5.2 mm. Eighty-five of the 110 patients had histologically residual tumor. The sensitivity, specificity, PPV, and NPV of tumor diagnosis were 63.5%, 92.0%, 96.4%, and 42.6%, respectively. Histological estimates of 54 (49.1%) MR-invisible vs. 56 (50.9%) MR-visible diagnoses were identified as 23 true-negative (TN) and 31 false-negative (FN) vs. 54 true-positive (TP) and 2 false-positive (FP). The recurrence-free rate was 98.1% in the MR-invisible group and 91.1% in the MR-visible group. The overall survival rates were 100% and 92.9%, respectively. CONCLUSION: A preoperative MR-invisible diagnosis in early-stage cervical cancer patients led to a high probability of FN and was associated with underdiagnosis.

Primary Gastric Small Cell Carcinoma: A Case Identified as a Large Subepithelial Tumor from Invisible State in 6 Months.

Primary gastric small cell carcinoma (GSCC) is one of the gastroenteropancreatic neuroendocrine tumors. It is a rare cancer with a very aggressive behavior and a poor prognosis because of the high rate of metastases. It is usually found in far advanced stage. We experienced a case of GSCC which had developed into a large subepithelial tumor (SET) from invisible state in a short period. A 65-year-old man consulted our hospital because of early gastric cancer. He underwent endoscopic submucosal dissection for the early gastric cancer at high body posterior wall. After 6 months, the follow-up endoscopy showed a large newly developed SET-like lesion with central ulceration at the gastric cardia. Endoscopic biopsy revealed GSCC. Total gastrectomy was performed. One out of the 26 perigastric lymph nodes had a metastasis. He received 6 cycles of adjuvant chemotherapy with etoposide and cisplatin. He is still in good health 12 months after operation.

Early Cervical Cancer: Predictive Relevance of Preoperative 3-Tesla Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: We assess the predictive significance of preoperative 3-Tesla multiparametric MRI findings. METHODS: A total of 260 patients with FIGO IA2-IIA cervical cancer underwent primary surgical treatment between 2007 and 2016. Univariable and multivariable logistic regression analyses were used to assess the incremental prognostic significance. RESULTS: The clinical predictive factors associated with pT2b disease were MRI parametrial invasion (PMI) (adjusted odds ratio (AOR) 3.77, 95% confidence interval(CI) 1.62-8.79; P=0.02) and MRI uterine corpus invasion (UCI) (AOR 9.99, 95% CI 4.11-24.32; P<0.0001). In multivariable analysis, for underdiagnoses, histologically squamous carcinoma versus adenocarcinoma and adenosquamous carcinoma (AOR 2.07, 95% CI 1.06-4.07; P=0.034) and MRI tumor size (AOR 0.76, 95% CI 0.63-0.92; P=0.005) were significant predictors; for overdiagnoses, these results were MRI tumor size (AOR 1.51, 95% CI 1.06-2.16; P=0.023), MRI PMI (AOR 71.73, 95% CI 8.89-611.38; P<0.0001) and MRI UCI (AOR 0.19, 95% CI 0.01-1.01; P=0.051). CONCLUSION: PMI and UCI on T2-weighted images through preoperative 3T MRI are useful coefficients for accurate prediction of the pT2b stage; however, careful surveillance is required. Therefore, preoperative decision-making for early cervical cancer patients based on MRI diagnosis should be considered carefully, particularly in the presence of factors that are known to increase the likelihood of misdiagnosis.

Low-Dose Radioactive Iodine Ablation Is Sufficient in Patients With Small Papillary Thyroid Cancer Having Minor Extrathyroidal Extension and Central Lymph Node Metastasis (T3 N1a).

PURPOSE: The aim of this study was to evaluate the effectiveness of low-dose radioactive iodine (RAI) ablation in patients with small papillary thyroid cancer (PTC) exhibiting microscopic extrathyroidal extension (mETE) and central lymph node (CLN) metastasis. METHODS: Among patients who underwent RAI ablation between March 2007 and February 2014, those who had small PTCs (≤2 cm), as well as mETE and CLN metastasis (T3 N1a M0), were enrolled. Response to ablation and long-term outcomes were assessed and compared according to the administered RAI dose. Factors associated with unsuccessful ablation were also determined. RESULTS: A total of 180 patients were included in the study. Eighty-eight patients had been treated with 1110 MBq (low-dose group) and 92 with 2960 MBq (high-dose group) of RAI. There were no significant differences in the responses to ablation (P = 0.810) and long-term outcomes (P = 0.663) between both groups. Among all patients enrolled, 13 did not achieve successful ablation at long-term follow-up. Logistic regression found that a high ratio of metastatic nodes was a significant factor for predicting unsuccessful ablation. CONCLUSIONS: Low-dose RAI ablation did not produce significantly different responses or long-term outcomes in patients with small PTCs exhibiting mETE and CLN metastasis. These findings suggest that low-dose ablation may be sufficient in this specific group of intermediate-risk patients, although careful selection is required for patients with a high ratio of metastatic nodes.

Polycomb protein EZH2 expression in diffuse large B-cell lymphoma is associated with better prognosis in patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone.

Polycomb group (PcG) proteins are evolutionarily conserved regulators of gene expression that contribute to normal lymphocyte development, and are involved in malignant transformation of these cells. Recently, BMI1 and EZH2 have been shown to be involved in lymphomagenesis and oncogenesis. We tried to elucidate the role of EZH2 as a prognostic factor for diffuse large B-cell lymphoma (DLBCL). High-level expression of EZH2 (EZH2 ≥ 70%) was associated with superior overall survival (OS) of 85.8% compared to low expression (EZH2 < 70%), with OS of 44.5% (p = 0.005). Subgroup analysis showed that the activated B-cell (ABC) subtype with high EZH2 expression had the highest overall survival (p = 0.011). In analysis of EZH2 expression within low International Prognostic Index (IPI) score, high EZH2 expression had a significant statistical correlation with longer OS (p = 0.034). With high IPI score, high EZH2 expression tended to be associated with longer OS (p = 0.130). Our results showed that EZH2 expression had a high prognostic relevance to survival outcomes. We demonstrated that DLBCL was associated with increased expression of the EZH2 PcG protein and Ki67. The distribution of EZH2 expression was wider than that of Ki67. In summary, increased EZH2 expression of tumor cells was associated with improvements in OS.

Ectomesenchymal chondromyxoid tumor in the anterior tongue: case report of a unique tumor.

Ectomesenchymal chondromyxoid tumor (ECMT) is a rare tumor, exclusively arising in the anterior tongue. Thirty-eight cases have been reported in the English literature. It usually presents as a sessile protrusion and shows round to spindle cells embedded in myxoid to chondroid stroma. Tumor cells are almost always positive for polyclonal glial fibrillary acidic protein (GFAP). We report our experience in the recent treatment of a case of ECMT, the third case in 3 years. The mass in the anterior tongue revealed characteristic morphologic features of ECMT and the expression of polyclonal GFAP. Although ECMT should be differentiated from other mesenchymal tumors including myoepithelioma, its clinical, morphological, and immunohistochemical features enable its diagnosis, especially when pathologists are aware of it.