Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Purpose: Acinar adenocarcinoma with mucinous components is a rare histologic variant of prostate cancer (PC) that was previously reported to exhibit more aggressive behavior than typical PC. However, recent studies have suggested that PC with mucinous components may not be more aggressive and could even have a more favorable prognosis. Therefore, this study investigated the clinical outcomes of PC with mucinous components. Materials and Methods: We reviewed 7,983 patients with PC who underwent radical prostatectomy between 2006 and 2019. Propensity score matching and Kaplan-Meier analyses were performed to compare outcomes between patients with typical PC (group 1) and those with PC containing mucinous components (group 2). Matching variables included age, initial prostate-specific antigen level, clinical stage, and pathological Gleason score (GS). Biochemical recurrence-free survival (BCRFS) and cancer-specific survival (CSS) were analyzed using Cox regression analysis to identify survival predictors. Results: Sixty-one patients (0.76%) had PC with mucinous components. No significant differences were observed in matched variables between the 2 groups. Pathological stage, lymph node invasion (LNI), and positive surgical margin rates were also comparable. At a median follow-up of 53 (interquartile range, 24–80) months, biochemical recurrence occurred in 29 patients in group 1 and 24 in group 2 (p=0.361). Two patients in group 1 and 3 in group 2 died from PC (p>0.999). BCRFS and CSS did not differ significantly between the 2 groups (p=0.676 and p=0.458, respectively). High GS (≥8) (p=0.007) and pT3b stage (p=0.035) were independent risk factors for BCRFS, while LNI (p=0.001) predicted CSS. The presence of mucinous components was not a significant predictor of either BCRFS or CSS (p=0.127 and p=0.561, respectively). Conclusion PC with mucinous components demonstrated clinical outcomes comparable to those of typical PC and was not an independent prognostic factor for survival. PC with mucinous components may not be as aggressive as previously believed.

Purpose: In men with metastatic castration-resistant prostate cancer (mCRPC), new bone lesions are sometimes not properly categorized through a confirmatory bone scan, and clinical significance of the test itself remains unclear. This study aimed to demonstrate the performance rate of confirmatory bone scans in a real-world setting and their prognostic impact in enzalutamide-treated mCRPC. Materials and Methods: Patients who received oral enzalutamide for mCRPC during 2014-2017 at 14 tertiary centers in Korea were included. Patients lacking imaging assessment data or insufficient drug exposure were excluded. The primary outcome was overall survival (OS). Secondary outcomes included performance rate of confirmatory bone scans in a real-world setting. Kaplan-Meier analysis and multivariate Cox regression analysis were performed. Results: Overall, 520 patients with mCRPC were enrolled (240 [26.2%] chemotherapy-naïve and 280 [53.2%] after chemotherapy). Among 352 responders, 92 patients (26.1%) showed new bone lesions in their early bone scan. Confirmatory bone scan was performed in 41 patients (44.6%), and it was associated with prolonged OS in the entire population (median, 30.9 vs. 19.7 months; p < 0.001), as well as in the chemotherapy-naïve (median, 47.2 vs. 20.5 months; p=0.011) and post-chemotherapy sub-groups (median, 25.5 vs. 18.0 months; p=0.006). Multivariate Cox regression showed that confirmatory bone scan performance was an independent prognostic factor for OS (hazard ratio 0.35, 95% confidence interval, 0.18 to 0.69; p=0.002). Conclusion Confirmatory bone scan performance was associated with prolonged OS. Thus, the premature discontinuation of enzalutamide without confirmatory bone scans should be discouraged.

Purpose: We investigated whether the use of a phosphodiesterase-5 inhibitor (PDE5i) after robot assited radical prostatectomy has a survival benefit over non-use patients because there are controversial results on the association between PDE5i use and survival outcomes for prostate cancer patients in literature. Materials and Methods: We designed a retrospective, matched, large-sample cohort study of 5,545 patients who underwent robot assisted radical prostatectomy (RARP) during 2013–2021 in a single institute. The exclusion criteria was patients who were aged >70 years at surgery, American Society of Anesthesiologists (ASA) physical status classification grade 4 or 5, history of other malignancies, patients who started PDE5i 6 months after survery and patients with follow up period less than 24 months after surgery. Among the 1,843 included patients, 1,298 were PDE5i users, and 545 were PDE5i non-users. We performed propensity score matching (PSM) of PDE5i users (n=529) with non-users (n=529) by adjusting for the variables of age, Gleason grade group, pathological T stage, preoperative ASA physical status grade, and International Index of Erectile Function score. Results: There were no significant difference in patient characteristics according to PSM. Kaplan–Meier curve revealed the difference of overall survival for PDE5i users and non-users (clustered log-rank test p<0.05). In a stratified Cox regression analysis, PDE5i use after RARP was associated with improved overall survival and reduced risk of death (hazard ratio 0.43; confidence interval 0.24–0.79; p=0.007). The limitation of this study was that the indication for the prescription of PDE5i was not given. Conclusions PDE5i administration after RARP were associated with overall survival of patients with prostate cancer. A further randomized control trial may reveal whether routine use of PDE5i after prostatectomy can improve survival of prostate cancer patient.

This case series study demonstrates the possibility of successful implant rehabilitation without bone augmentation in the atrophic posterior maxilla with cystic lesion in the sinus. Sinus lift without bone graft using the lateral approach was performed. In one patient, the cyst was aspirated and simultaneous implantation under local anesthesia was performed, whereas the other cyst was removed under general anesthesia, and the sinus membrane was elevated in a second process, followed by implantation. In both cases, tapered 11.5-mm-long implants were utilized. With all of the implants, good stability and appropriate bone height were achieved. The mean bone level gain was 5.73 mm; adequate bone augmentation around the implants was shown, the sinus floor was moved apically, and the cyst was no longer radiologically detected. Completion of all of the treatments required an average of 12.5 months. The present study showed that sufficient bone formation and stable implantation in a maxilla of insufficient bone volume are possible through sinus lift without bone materials. The results serve to demonstrate, moreover, that surgical treatment of mucous retention cyst can facilitate rehabilitation. These techniques can reduce the risk of complications related to bone grafts, save money, and successfully treat antral cyst.
Anesthesia, General ; Anesthesia, Local ; Dental Implants ; Humans ; Maxilla ; Maxillary Sinus* ; Membranes* ; Osteogenesis ; Rehabilitation* ; Sinus Floor Augmentation ; Transplants

PURPOSE: Transducin-like enhancer of split 1 (TLE1) is a member of the TLE family of transcriptional co-repressors that control the transcription of a wide range of genes. We investigated the prognostic significance of TLE1 protein expression in breast cancers by using immunohistochemistry and explored the relationship of TLE1 with clinicopathological parameters. METHODS: Immunohistochemistry was performed on 456 cases of breast cancer tiled on tissue microarrays. The relationship between TLE1 expression in normal breast specimens and ductal carcinoma in situ (DCIS) was also analyzed. RESULTS: TLE1 was highly expressed in 57 of 456 (12.5%) carcinoma samples. TLE1 was more frequently expressed in DCIS and invasive breast cancers than in normal breast tissue (p=0.002). High expression of TLE1 significantly correlated with negative lymph node (LN) metastasis (p=0.007), high histologic grade (p<0.001), estrogen receptor negativity (p<0.001), progesterone receptor negativity (p<0.001), human epidermal growth factor receptor 2 (HER2) positivity (p<0.001), and high Ki-67 proliferation index (p<0.001). Based on intrinsic subtypes, high TLE1 expression was strongly associated with HER2+ and triple-negative breast cancers (TNBC) (p<0.001). Survival analysis demonstrated no significant association between TLE1 expression and disease-free survival (DFS) (p=0.167) or overall survival (OS) (p=0.286). In subgroup analyses, no correlation was found between TLE1 expression and DFS or OS according to LN status or intrinsic subtype. CONCLUSION: High TLE1 expression is significantly associated with the HER2+ and TNBC subtypes. This is the first study documenting immunohistochemical expression of TLE1 in invasive breast cancer and its association with clinicopathological parameters, prognosis, and intrinsic subtype.
Breast Neoplasms* ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Co-Repressor Proteins ; Disease-Free Survival ; Estrogens ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Triple Negative Breast Neoplasms

Sialolithiasis, the most common salivary gland pathology, is caused by calculi in the gland itself and its duct. While patients with small sialoliths can undergo conservative treatment, those with standard-size or larger sialoliths require sialolithotomy. In the present case study, we removed two sialoliths located beneath the mucosa in the posterior and anterior regions of Wharton's duct, respectively. For the posterior calculus, we performed sialolithotomy via an intra-oral approach; thereafter, the small anterior calculus near the duct orifice was removed by hydraulic power. This method has not previously been reported. There were no complications either during the operation or postoperatively, and the salivary function of the gland remained normal.
Calculi* ; Humans ; Methods* ; Mucous Membrane ; Needles* ; Pathology ; Salivary Ducts ; Salivary Gland Calculi ; Salivary Glands ; Submandibular Gland

PURPOSE: The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance. METHODS: IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed. RESULTS: High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045). CONCLUSION: EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression. Furthermore, EZH2 may be a prognostic marker, especially in patients with luminal A cancer.
Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Catalytic Domain ; Estrogens ; Histones ; Humans ; Immunohistochemistry ; Keratins ; Phenobarbital* ; Polycomb Repressive Complex 2 ; Prognosis ; Receptor, Epidermal Growth Factor ; Retrospective Studies

PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas. RESULTS: High PD-L1 expression was demonstrated in 63 of 465 tumors (13.5%). High PD-L1 expression was significantly associated with high histologic grade (p<0.001), negative lymph nodes (p=0.011), early pathologic stage (p=0.025), high tumor-infiltrating lymphocyte (TIL) (p<0.001) counts, negative estrogen receptor (p<0.001) and progesterone receptor (p=0.002) expression, positive human epidermal growth factor receptor 2 (HER2) (p=0.003), cytokeratin 5/6 (p=0.011), epidermal growth factor receptor (p<0.001), and p53 (p<0.001) expression, and high Ki-67 proliferating index (p<0.001). Based on intrinsic subtypes, high PD-L1 expression and high TIL counts were significantly associated with the HER2 and triple-negative basal type (p<0.001). PD-L1 expression was significantly associated with better disease-free survival (DFS) (p=0.041) and overall survival (OS) (p=0.026) in the univariate analysis, but not in the multivariate analysis. Higher TIL levels was an independent prognostic factor for decreased disease progression (hazard ratio [HR], 2.389; 95% confidence interval [CI], 1.284–4.445; p=0.006) and overall death (HR, 3.666; 95% CI, 1.561–8.607; p=0.003). CONCLUSION: PD-L1 protein expression in breast cancer is associated with better DFS and OS, but is not an independent prognostic factor. High PD-L1 expression was significantly associated with high TIL levels. This finding has important implications for antibody therapies targeting the PD-1/PD-L1 signaling mechanism in breast cancer.
Breast Neoplasms* ; Breast* ; Disease Progression ; Disease-Free Survival ; Estrogens ; Humans ; Immunohistochemistry ; Keratins ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating* ; Multivariate Analysis ; Prognosis* ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

PURPOSE: PIK3CA is often mutated in a variety of malignancies, including colon, gastric, ovary, breast, and brain tumors. We investigated PIK3CA expression in gastric cancer and explored the relationships between the PIK3CA expression level and clinicopathological features as well as survival of the patients. MATERIALS AND METHODS: We examined PIK3CA expression in a tissue microarray of 178 gastric adenocarcinomas by immunohisto-chemistry and reviewed patients' medical records. RESULTS: In our study, 112 of the 178 gastric cancer patients displayed positive PIK3CA expression. Overexpression of PIK3CA was correlated with low grade differentiation (P=0.001), frequent lymphatic invasion (P=0.032), and high T stage (P=0.040). Patients with positive PIK3CA staining were more likely to display worse overall survival rate than those with negative PIK3CA staining, as determined by Kaplan-Meier survival analysis with log-rank test (P=0.047) and a univariate analysis using the Cox proportional hazard model (hazard ratio=1.832, P=0.051). CONCLUSIONS: Elevated PIK3CA expression was significantly correlated with tumor invasiveness, tumor phenotypes, and poor patient survival.
Adenocarcinoma ; Brain Neoplasms ; Breast ; Colon ; Female ; Humans ; Immunohistochemistry ; Medical Records ; Ovary ; Phenotype ; Proportional Hazards Models ; Stomach Neoplasms* ; Survival Rate