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1.
Chirurgia (Bucur) ; 119(2): 218-226, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38743835

ABSTRACT

Introduction: Acute intestinal obstruction secondary to extensive peritoneal carcinomatosis is an end stage event. The role of palliative surgery in these patients is debatable in view of the anticipated severe complications and its doubtful role in achieving adequate palliation. The primary objective of our study was to evaluate the feasibility and ability of patients to resume oral nutrition after palliative surgery for acute intestinal obstruction due to peritoneal carcinomatosis. Patients and Methods: It is an observational study in which we retrospectively reviewed the data from a prospectively maintained clinical database of 40 patients. The predefined pre- and intraoperative variables were obtained. The immediate outcome variables like postoperative complications, length of hospital stay, and mortality were analyzed. The short-term outcomes at 3 months in the form of survival, ability to resume enteral nutrition were analyzed. Results: Among the 40 patients 18 were males and 22 females. Ovarian cancer was the most common primary (27.5%) in the study. Twelve patients had acute intestinal obstruction as their first presentation without any past events and 25 (62.5%) patients had been operated on previously or received adjuvant systemic treatment. The palliative surgical option was technically feasible in 37 (93.5%) patients. The median length of hospitalization for the patients who were discharged was 10 days with a range of 6-18 days. Six (15%) patients died in the postoperative period. Severe post-operative complications were seen in 9 (26.4%) patients. Among the patients (n=34) discharged 26 (76.4%) were alive at 3 months. In those who were alive, 21 (80.7%) of them were on some form of oral nutrition at 3 months. Conclusion: Palliative surgery in patients with acute intestinal obstruction secondary to peritoneal carcinomatosis is feasible with acceptable morbidity and mortality. The enteral nutrition can be restored in the majority of these patients.


Subject(s)
Feasibility Studies , Intestinal Obstruction , Length of Stay , Palliative Care , Peritoneal Neoplasms , Humans , Male , Female , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Palliative Care/methods , Retrospective Studies , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/complications , Peritoneal Neoplasms/surgery , Middle Aged , Treatment Outcome , Aged , Adult , Carcinoma/surgery , Carcinoma/complications , Carcinoma/secondary , Carcinoma/mortality , Aged, 80 and over , Ovarian Neoplasms/surgery , Ovarian Neoplasms/complications
2.
Sci Rep ; 14(1): 9898, 2024 04 30.
Article in English | MEDLINE | ID: mdl-38688967

ABSTRACT

The clinical significance of the combination of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.


Subject(s)
Blood Platelets , Lymphocytes , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neutrophils , Humans , Male , Female , Neutrophils/pathology , Retrospective Studies , Middle Aged , Prognosis , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/blood , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/blood , Lymphocytes/pathology , Blood Platelets/pathology , Adult , Aged , ROC Curve , Platelet Count , Lymphocyte Count , Carcinoma/blood , Carcinoma/mortality , Carcinoma/pathology , Young Adult
3.
Radiother Oncol ; 196: 110311, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38670263

ABSTRACT

OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.


Subject(s)
Carcinoma , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Humans , Male , Female , Retrospective Studies , Middle Aged , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Carcinoma/radiotherapy , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/mortality , Carcinoma/radiotherapy , Carcinoma/secondary , Carcinoma/mortality , Adult , Aged , Propensity Score , Prognosis , Survival Rate , Bone Neoplasms/secondary , Bone Neoplasms/radiotherapy , Bone Neoplasms/mortality , Lung Neoplasms/radiotherapy , Lung Neoplasms/pathology , Lung Neoplasms/mortality , Treatment Outcome , Liver Neoplasms/secondary , Liver Neoplasms/radiotherapy , Liver Neoplasms/mortality
4.
Radiother Oncol ; 194: 110189, 2024 May.
Article in English | MEDLINE | ID: mdl-38432309

ABSTRACT

BACKGROUND AND PURPOSE: Whether concurrent chemoradiotherapy would provide survival benefits in patients with stage II and T3N0 NPC with adverse factors remains unclear in IMRT era. We aimed to assess the value of concurrent chemotherapy compared to IMRT alone in stage II and T3N0 NPC with adverse features. MATERIALS AND METHODS: 287 patients with stage II and T3N0 NPC with adverse factors were retrospectively analyzed, including 98 patients who received IMRT alone (IMRT alone group) and 189 patients who received cisplatin-based concurrent chemotherapy (CCRT group). The possible prognostic factors were balanced using propensity score matching (PSM). Kaplan-Meier analysis was used to evaluate the survival rates, and log-rank tests were employed to compare differences between groups. RESULTS: The median follow-up duration was 90.8 months (interquartile range = 75.6-114.7 months). The IMRT alone and the CCRT group were well matched; however, for all survival-related endpoints, there were no significant differences between them (5-year failure-free survival: 84.3% vs. 82.7%, P value = 0.68; 5-year overall survival: 87.3% vs. 90.6%, P value = 0.11; 5-year distant metastasis-free survival: 92.8% vs. 92.5%, P value = 0.97; 5-year locoregional relapse-free survival: 93.4% vs. 89.9%, P value = 0.30). The incidence of acute toxicities in the IMRT alone group was significantly lower than that in the CCRT group. CONCLUSION: For patients with stage II and T3N0 NPC with adverse features treated using IMRT, no improvement in survival was gained by adding concurrent chemotherapy; however, the occurrence of acute toxicities increased significantly. For those combined with non-single adverse factors, the comprehensive treatment strategy needs further exploration.


Subject(s)
Chemoradiotherapy , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Neoplasm Staging , Propensity Score , Radiotherapy, Intensity-Modulated , Humans , Male , Female , Chemoradiotherapy/adverse effects , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/mortality , Middle Aged , Nasopharyngeal Carcinoma/therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Retrospective Studies , Adult , Radiotherapy, Intensity-Modulated/adverse effects , Cisplatin/therapeutic use , Cisplatin/administration & dosage , Cohort Studies , Survival Rate , Carcinoma/therapy , Carcinoma/pathology , Carcinoma/mortality , Aged
5.
Cancer Biother Radiopharm ; 38(2): 116-121, 2023 Mar.
Article in English | MEDLINE | ID: mdl-32783641

ABSTRACT

Objective: LncRNA IUR has been recently identified as a key regulator of Bcr-Abl-induced tumorigenesis, while its role in gastric carcinoma (GC) is unknown. This study investigated the involvement of IUR in GC. Materials and Methods: Gene expression levels were measured by performing quantitative polymerase chain reaction. Interactions between IUR and ROCK1 were analyzed by transfection experiments. Cell invasion and migration were analyzed by Transwell assay. Results: In this study, the authors showed that IUR was downregulated in GC. A follow-up study showed that low IUR expression levels predicted poor survival. In GC tissues, ROCK1 was upregulated in GC tissues and inversely correlated with IUR. In GC cells, IUR overexpression mediated the downregulation of ROCK1. ROCK1 overexpression resulted in increased GC cell invasion and migration, while IUR overexpression played an opposite role. Conclusion: IUR is downregulated in GC and inhibits GC cell invasion and migration by downregulating ROCK1.


Subject(s)
Carcinoma , MicroRNAs , RNA, Long Noncoding , Stomach Neoplasms , Humans , Carcinoma/genetics , Carcinoma/mortality , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Follow-Up Studies , Gene Expression Regulation, Neoplastic , MicroRNAs/metabolism , rho-Associated Kinases/genetics , rho-Associated Kinases/metabolism , RNA, Long Noncoding/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality
6.
BMC Cancer ; 22(1): 242, 2022 Mar 05.
Article in English | MEDLINE | ID: mdl-35248011

ABSTRACT

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-positive tumors are defined by protein overexpression (3+) or gene amplification using immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), respectively. HER2-positive tumors have historically included both IHC(3+) and IHC(2+, equivocal)/FISH(+) tumors and received the same treatment. Differences in biology between these two tumor types, however, are poorly understood. Considering anti-HER2 drugs bind directly to HER2 protein on the cell surface, we hypothesized anti-HER2 therapies would be less effective in IHC(2+)/FISH(+) tumors than in IHC(3+) tumors, leading to differences in patient outcomes. METHODS: A total of 447 patients with HER2-positive invasive carcinoma who underwent curative surgery were retrospectively investigated. HER2 status was assessed in surgical specimens, except in patients who received neo-adjuvant chemotherapy, where biopsy specimens were employed. RESULTS: Age, tumor size, lymph node status and ER status were independent factors relating to disease-free-survival, but no difference was observed between IHC(3+) and IHC(2+)/FISH(+) tumors. Kaplan-Meier analysis found patient outcomes did not differ, even after stratifying into those that did (n = 314), or did not (n = 129), receive chemotherapy with anti-HER2 drugs. In 134 patients who received NAC, pathological complete response rates in IHC(3+) and IHC(2+)/FISH(+) tumors were 45% and 21%, respectively. Survival after developing metastasis was significantly shorter in the IHC(2+)/FISH(+) group. CONCLUSIONS: The prognosis of patients with IHC(2+)/FISH(+) tumors did not differ from IHC(3+) tumors. However, the significance of HER2 protein overexpression in relation to treatment response remains unclear and warrants further investigations.


Subject(s)
Breast Neoplasms/genetics , Carcinoma/genetics , Gene Amplification/genetics , Gene Expression/genetics , Receptor, ErbB-2/metabolism , Biomarkers, Tumor/genetics , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Carcinoma/mortality , Carcinoma/therapy , Chemotherapy, Adjuvant , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome
7.
Anticancer Res ; 42(3): 1571-1577, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35220254

ABSTRACT

BACKGROUND/AIM: The optimal timing of switching from platinum-based chemotherapy to pembrolizumab in patients with advanced urothelial carcinoma (UC) remains unclear. PATIENTS AND METHODS: Thirty-four patients who received pembrolizumab as second-line treatment after first-line platinum-based chemotherapy were retrospectively evaluated. RESULTS: According to overall survival (OS) from pembrolizumab, there was a significant difference between ≤4 and >4 prior chemotherapy cycles (7.0 and 25.5 months, p=0.034), but not between ≤6 and >6 cycles (11.3 and 6.6 months, p=0.658). According to the Cox proportional hazards regression model, the number of chemotherapy cycles was not correlated with better OS in pembrolizumab-treated patients. According to the OS from the first-line treatment, there was a significant difference between ≤4 and >4 prior chemotherapy cycles (17.3 and 37.1 months, p<0.001), but not between ≤6 and >6 cycles (18.6 and 27.3 months, p=0.276). CONCLUSION: The optimal timing of switching from platinum-base chemotherapy to pembrolizumab in advanced UC is around six cycles.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma/drug therapy , Drug Substitution , Immune Checkpoint Inhibitors/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma/mortality , Carcinoma/pathology , Drug Substitution/adverse effects , Drug Substitution/mortality , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Japan , Male , Middle Aged , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
8.
Anticancer Res ; 42(3): 1629-1634, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35220261

ABSTRACT

BACKGROUND/AIM: This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups. The factors associated with survival were also investigated. RESULTS: The objective response rate was significantly lower in the group with PPIs compared with the group without PPIs. Both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the group with PPIs than in the group without PPIs. The use of PPIs was a significant predictor of poor PFS and OS in multivariate analysis. CONCLUSION: The use of PPIs was negatively associated with tumor response and survival in patients with advanced UC treated with pembrolizumab.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Carcinoma/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Proton Pump Inhibitors/therapeutic use , Urinary Bladder Neoplasms/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/adverse effects , Carcinoma/immunology , Carcinoma/mortality , Carcinoma/pathology , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Male , Progression-Free Survival , Proton Pump Inhibitors/adverse effects , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
9.
BMC Cancer ; 22(1): 10, 2022 Jan 03.
Article in English | MEDLINE | ID: mdl-34979987

ABSTRACT

BACKGROUND: New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increased levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers. METHODS: Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results. RESULTS: We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12-2.85, p <0.001). Subgroup analysis showed that high expression levels of SNHG7 were also significantly associated with unfavorable OS in digestive system cancer (HR = 2.31, 95% CI: 1.90-2.80, p <0.001) and non-digestive system cancer (HR = 2.67, 95% CI: 2.12-3.37, p <0.001). Additionally, increased SNHG7 expression was found to be associated with tumor stage and progression (III/IV vs. I/II: HR = 1.76, 95% CI: 1.57-1.98, p <0.001). Furthermore, elevated SNHG7 expression significantly predicted lymph node metastasis (LNM) (HR = 1.98, 95% CI: 1.74-2.26, p <0.001) and distant metastasis (DM) (HR = 2.49, 95% CI: 1.88-3.30, p <0.001) respectively. No significant heterogeneity was observed among these studies. SNHG7 was significantly upregulated in four cancers and the elevated expression of SNHG7 predicted shorter OS in four cancers, worse DFS in five malignancies and worse PFI in five carcinomas based on the validation using the GEPIA on-line analysis tool. CONCLUSIONS: The present analysis suggests that elevated SNHG7 is significantly associated with unfavorable OS, tumor progression, LNM and DM in various carcinomas, and may be served as a promising biomarker to guide therapy for cancer patients.


Subject(s)
Carcinoma/genetics , Carcinoma/mortality , Neoplasms/genetics , Neoplasms/mortality , RNA, Long Noncoding/genetics , Biomarkers, Tumor/genetics , Computational Biology , Humans , Lymphatic Metastasis/genetics , Predictive Value of Tests , Prognosis , Proportional Hazards Models
10.
Sci Rep ; 12(1): 862, 2022 01 17.
Article in English | MEDLINE | ID: mdl-35039565

ABSTRACT

Individual cell types of human tissues have their own CpG site methylation profiles, which might be utilized for the development of methylation markers to denote tumor-infiltrating lymphocytes (TILs). We aimed to develop DNA methylation markers that recapitulate the densities of TILs in gastric carcinoma (GC). Through genome-wide methylation profiling, NCOR2, PARK2, and ZSCAN12 were found to be highly methylated in CD3-positive and CD8-positive cells and rarely methylated in tumor cells. Scores of the three methylation markers were analyzed for their relationship with the overall survival and recurrence-free survival of patients with advanced GC (n = 471). The scores of three methylation markers were closely associated with densities of CD3-positive or CD8-positive cells at the tumor center or invasive front of GCs and found to be a significant prognostic factor in univariate analysis of overall survival and recurrence-free survival. In multivariate analysis, the highest score showed hazard ratios of 0.513 (CI 0.306-0.857) and 0.434 (CI 0.261-0.720) for overall survival and recurrence-free survival, respectively. The findings suggest that methylation markers signifying TILs might be utilized for the recapitulation of TIL density in GCs and serve as biomarkers for predicting prognosis in patients with GC.


Subject(s)
Carcinoma/genetics , Carcinoma/pathology , DNA Methylation/genetics , Kruppel-Like Transcription Factors/genetics , Kruppel-Like Transcription Factors/metabolism , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Nuclear Receptor Co-Repressor 2/genetics , Nuclear Receptor Co-Repressor 2/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Biomarkers/metabolism , CD8-Positive T-Lymphocytes/metabolism , Carcinoma/mortality , Female , Forecasting , Humans , Male , Middle Aged , Prognosis , Stomach Neoplasms/mortality , Survival Rate , Tumor Microenvironment/genetics
11.
Diagn Pathol ; 17(1): 5, 2022 Jan 07.
Article in English | MEDLINE | ID: mdl-34996485

ABSTRACT

BACKGROUND: According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated. METHODS: 195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed. RESULTS: 183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn't receive targeted therapy. CONCLUSIONS: In this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Carcinoma/diagnosis , Carcinoma/genetics , In Situ Hybridization, Fluorescence , Receptor, ErbB-2/genetics , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma/mortality , Carcinoma/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Practice Guidelines as Topic , Prognosis , Survival Analysis
12.
Sci Rep ; 12(1): 1238, 2022 01 24.
Article in English | MEDLINE | ID: mdl-35075138

ABSTRACT

The phase III MAX clinical trial randomised patients with metastatic colorectal cancer (mCRC) to receive first-line capecitabine chemotherapy alone or in combination with the anti-VEGF-A antibody bevacizumab (± mitomycin C). We utilised this cohort to examine whether single nucleotide polymorphisms (SNPs) in VEGF-A, VEGFR1, and VEGFR2 are predictive of efficacy outcomes with bevacizumab or the development of hypertension. Genomic DNA extracted from archival FFPE tissue for 325 patients (69% of the MAX trial population) was used to genotype 16 candidate SNPs in VEGF-A, VEGFR1, and VEGFR2, which were analysed for associations with efficacy outcomes and hypertension. The VEGF-A rs25648 'CC' genotype was prognostic for improved PFS (HR 0.65, 95% CI 0.49 to 0.85; P = 0.002) and OS (HR 0.70, 95% CI 0.52 to 0.94; P = 0.019). The VEGF-A rs699947 'AA' genotype was prognostic for shorter PFS (HR 1.32, 95% CI 1.002 to 1.74; P = 0.048). None of the analysed SNPs were predictive of bevacizumab efficacy outcomes. VEGFR2 rs11133360 'TT' was associated with a lower risk of grade ≥ 3 hypertension (P = 0.028). SNPs in VEGF-A, VEGFR1 and VEGFR2 did not predict bevacizumab benefit. However, VEGF-A rs25648 and rs699947 were identified as novel prognostic biomarkers and VEGFR2 rs11133360 was associated with less grade ≥ 3 hypertension.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Colorectal Neoplasms/drug therapy , Receptors, Vascular Endothelial Growth Factor/genetics , Vascular Endothelial Growth Factor A/genetics , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Carcinoma/genetics , Carcinoma/mortality , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Female , Humans , Hypertension/genetics , Male , Middle Aged , Pharmacogenomic Variants , Polymorphism, Single Nucleotide
13.
Sci Rep ; 12(1): 1222, 2022 01 24.
Article in English | MEDLINE | ID: mdl-35075167

ABSTRACT

The significance of N6-methyladenosine (m6A) RNA modifications in the progression of breast cancer (BC) has been recognised. However, their potential role and mechanism of action in the tumour microenvironment (TME) and immune response has not been demonstrated. Thus, the role of m6A regulators and their downstream target gene components in BC remain to be explored. In this study, we used a series of bioinformatics methods and experiments to conduct exploratory research on the possible role of m6A regulators in BC. First, two regulatory modes of immune activation and inactivation were determined by tumour classification. The TME, immune cell infiltration, and gene set variation analysis results confirmed the reliability of this pattern. The prognostic model of the m6A regulator was established by the least absolute shrinkage and selection operator and univariate and multivariate Cox analyses, with the two regulators most closely related to survival verified by real-time quantitative reverse transcription polymerase chain reaction. Next, the prognostic m6A regulator identified in the model was crossed with the differential copy number of variant genes in invasive BC (IBC), and it was determined that YTHDF1 was a hub regulator. Subsequently, single-cell analysis revealed the expression patterns of m6A regulators in different IBC cell populations and found that YTHDF1 had significantly higher expression in immune-related IBC cells. Therefore, we selected the intersection of the BC differential expression gene set and the differential expression gene set of a cell line with knocked-down YTHDF1 in literature to identify downstream target genes of YTHDF1, in which we found IFI6, EIR, and SPTBN1. A polymerase chain reaction was conducted to verify the results. Finally, we confirmed the role of YTHDF1 as a potential prognostic biomarker through pan-cancer analysis. Furthermore, our findings revealed that YTHDF1 can serve as a new molecular marker for BC immunotherapy.


Subject(s)
Adenosine/analogs & derivatives , Breast Neoplasms/metabolism , Carcinoma/metabolism , RNA/metabolism , Tumor Microenvironment , Adenosine/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Carcinoma/drug therapy , Carcinoma/immunology , Carcinoma/mortality , Case-Control Studies , Humans , Lymphocytes, Tumor-Infiltrating , Molecular Targeted Therapy , Prognosis , RNA-Binding Proteins/metabolism
14.
Diagn Pathol ; 17(1): 1, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34986845

ABSTRACT

BACKGROUND: Breast cancer is one of the most common types of cancer. Ribonucleotide reductase (RNR) is a heterodimeric tetramer consisting of two Ribonucleoside-diphosphate reductase large subunits (RRM1) and two Ribonucleoside-diphosphate reductase small subunits (RRM2). RRM2 is the building subunit of RNR that is important for synthesis of Deoxynucleoside triphosphate (dNTP) during S phase of cell cycle during DNA replication. RRM2 is associated with poor prognosis in lung and colorectal cancer. In breast cancer, increased RRM2 protein level is strongly correlated with large tumour size, positive lymph node and relapse. In this study, we aimed to study expression of RRM2 in breast cancer and to correlate it with different clinicopathological parameters in Egyptian women. MATERIAL AND METHODS: This study was performed by investigating RRM2 protein expression in breast cancer and correlating the results with other clinicopathological variables using immunohistochemistry and tissue microarrays. RESULTS: About 77% of cases were RRM2 positive. High Ki67 was observed in cases with high RRM2 score. The majority of non-luminal cases expressed RRM2, however this was statistically insignificant. In ER positive group, RRM2 expression was associated with shorter disease free survival with borderline significance. CONCLUSION: RRM2 protein expression can help in evaluating outcome of breast cancer patients and could be a potential therapeutic target.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms/diagnosis , Carcinoma/diagnosis , Ribonucleoside Diphosphate Reductase/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Carcinoma/metabolism , Carcinoma/mortality , Egypt , Female , Humans , Immunohistochemistry , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Tissue Array Analysis
15.
Anticancer Res ; 42(2): 981-989, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35093898

ABSTRACT

BACKGROUND/AIM: The efficacy of programmed cell death 1 (PD-1) inhibitor therapy for patients with recurrent and/or metastatic salivary gland carcinoma (R/M SGC) remains unclear. PATIENTS AND METHODS: We retrospectively analyzed 36 patients with R/M SGC treated with PD-1 inhibitor. The expression of programmed cell death ligand 1 (PD-L1) and mismatch repair (MMR) proteins was also analyzed. RESULTS: The objective response rate (ORR) was 11.1%. The histopathological subtypes of patients who achieved complete response or partial response were salivary duct carcinoma (SDC) in three patients and poorly differentiated carcinoma in one patient, all of whom showed a positive PD-L1 expression. The expression of MMR proteins was not associated with the efficacy of PD-1 inhibitors. CONCLUSION: Although the efficacy of PD-1 inhibitor therapy in R/M SGC is limited, certain patients may respond and achieve long-term disease control. There is a potential therapeutic effect in SDC patients with positive PD-L1 expression.


Subject(s)
Carcinoma/drug therapy , Immune Checkpoint Inhibitors/therapeutic use , Salivary Gland Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , B7-H1 Antigen/metabolism , Carcinoma/metabolism , Carcinoma/mortality , Carcinoma/pathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/mortality , Salivary Gland Neoplasms/pathology , Survival Analysis , Treatment Outcome
16.
Mod Pathol ; 35(1): 33-43, 2022 01.
Article in English | MEDLINE | ID: mdl-34518631

ABSTRACT

Low-grade neuroendocrine carcinoma of the skin (LGNECS) was proposed in 2017 as a new primary cutaneous neoplasm with neuroendocrine differentiation; however, it is not yet well known due to its rarity. Herein, we perform a detailed clinicopathologic analysis of 13 cases as well as panel DNA sequencing in three cases. The study included 12 males and 1 female with a median age of 71 (43-85) years. All lesions occurred on the ventral trunk. The mean tumor size was 2.2 (0.8-11.0) cm. The histopathology resembled that of well-differentiated neuroendocrine tumors (NETs) in other organs, but intraepidermal pagetoid spreading was seen in 8 (61.5%) cases and stromal mucin deposits in 4 (30.8%). Immunoreactivity for CK7, CK19, EMA, BerEP4, CEA, chromogranin A, synaptophysin, INSM1, GCDFP15, GATA3, ER, and bcl-2 were present in varying degrees in all tested cases. PTEN c.165-1G>A splice site mutation was detected by panel sequencing in one case, and GATA3 P409fs*99 and SETD2 R1708fs*4 in another case. Lymph node metastasis was seen significantly in cases with tumor size >2.0 cm [8/8 (100%) vs. 1/5 (20%)]. All three cases with size >3.0 cm were in unresectable advanced-stage [3/3 (100%) vs. 1/10 (10%)], and two of the three patients succumbed to the disease. The two cases of death revealed mild nuclear atypia (mitosis: 1/10 HPFs) and moderate nuclear atypia (2/10 HPFs). Thus, tumor size would be a better prognostic factor than nuclear atypia, mitotic count, and Ki67 index, unlike in NETs. These clinicopathologic and immunohistochemical features would represent the characteristics as skin adnexal tumors with apocrine/eccrine differentiation rather than NETs; therefore, we rename it as sweat-gland carcinoma with neuroendocrine differentiation (SCAND).


Subject(s)
Carcinoma, Neuroendocrine/pathology , Carcinoma/pathology , Sweat Gland Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma/genetics , Carcinoma/mortality , Carcinoma, Neuroendocrine/genetics , Carcinoma, Neuroendocrine/mortality , Female , Humans , Immunohistochemistry , Lymphatic Metastasis/pathology , Male , Middle Aged , Sweat Gland Neoplasms/genetics , Sweat Gland Neoplasms/mortality
17.
J Cancer Res Clin Oncol ; 148(2): 517-525, 2022 Feb.
Article in English | MEDLINE | ID: mdl-33860848

ABSTRACT

PURPOSE: As a common head and neck tumor, laryngeal cancer has attracted heightened attention for its treatment and prognosis. Surgery and radiotherapy were mainly therapeutic approaches in laryngeal cancer, and intensity-modulated radiotherapy (IMRT) was a precision treatment way in radiotherapy. However, the therapeutic effect of surgery plus IMRT in laryngeal cancer was rarely reported. This study aims to determine the effect of IMRT on the treatment of patients with laryngeal cancer. METHODS: A total of 125 patients with laryngeal cancer were collected and retrospectively analyzed based on their clinical data and follow-up results. These patients had a clear treatment plan for surgery and intensity-modulated radiotherapy. RESULTS: Smoking, lymph node metastasis, TNM staging and therapeutic approaches could affect the survival of patients with laryngeal cancer. It was shown that the laryngeal function retention rate in the simple IMRT group was significantly higher than the simple surgery group and surgery plus IMRT group. The 5-year survival rate of surgery plus IMRT, simple surgery and simple IMRT were 82.86%, 53.85% and 43.33%, respectively. The locoregional recurrences rate of surgery plus IMRT, simple surgery and simple IMRT were 14.29%, 34.62% and 43.33%. CONCLUSION: Surgery plus IMRT was a feasible and efficacious treatment technique for patients with laryngeal cancer, which effectively prolong the survival time of patients.


Subject(s)
Carcinoma , Laryngeal Neoplasms , Laryngectomy , Radiotherapy, Intensity-Modulated , Adult , Aged , Aged, 80 and over , Carcinoma/mortality , Carcinoma/pathology , Carcinoma/radiotherapy , Carcinoma/surgery , China/epidemiology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Laryngeal Neoplasms/mortality , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Laryngectomy/methods , Laryngectomy/mortality , Laryngectomy/statistics & numerical data , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/etiology , Prognosis , Radiotherapy Dosage , Radiotherapy, Intensity-Modulated/mortality , Radiotherapy, Intensity-Modulated/statistics & numerical data , Retrospective Studies , Survival Rate , Treatment Outcome
18.
J Surg Oncol ; 125(3): 399-404, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34689332

ABSTRACT

BACKGROUND: Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT). METHODS: MDT patients with complex gallbladder disease were included. Collated data included demographics, MDT discussion, operative details, and patient outcomes. RESULTS: A total of 454 patients with complex gallbladder disease were reviewed, 48 (10.6%) were offered radical surgery for suspected cancer. Twenty-five underwent frozen section that led to radical surgery in 6 (25%). All frozen sections were congruent with final histopathology but doubled the operating time (p < 0.0001). Both the surgeon's subjective and additional frozen section's objective assessment, allowed for de-escalation of unnecessary radical surgery, comparing favourably to a 13.0% cancer diagnosis among radical surgery historically. CONCLUSIONS: The MDT process was highly sensitive in identifying gallbladder cancers but lacked specificity. The surgeon's intraoperative assessment is paramount in suspected cancers, and deescalated unnecessary radical surgery. Intraoperative frozen section was a safe and viable adjunct at a cost of resources and operative time.


Subject(s)
Carcinoma/pathology , Carcinoma/surgery , Cholecystectomy , Frozen Sections , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Aged , Carcinoma/mortality , Female , Gallbladder Neoplasms/mortality , Humans , Lymphoma/mortality , Lymphoma/pathology , Lymphoma/surgery , Male , Melanoma/mortality , Melanoma/pathology , Melanoma/surgery , Middle Aged , Neoplasm Staging , Operative Time , Retrospective Studies , Sensitivity and Specificity , Survival Rate
19.
Am J Surg Pathol ; 46(1): 11-17, 2022 01 01.
Article in English | MEDLINE | ID: mdl-34334690

ABSTRACT

The development of somatic-type malignancies (SMs) in testicular germ cell tumors (GCTs) is a rare but well-recognized phenomenon. We studied the pathologic features of 63 GCTs with SMs in the testis (n=22) or metastases (n=41) and correlated these features with clinical outcomes. The patients with SMs in the testis (median age, 26 y) were younger than those with metastatic SMs (median age, 38.5 y). The SMs consisted of carcinomas (n=21), sarcomas (n=21), primitive neuroectodermal tumors (n=15), nephroblastomas (n=3), and mixed tumors (n=3). Sarcoma was the most common SM in the testis (n=11), and most sarcomas were rhabdomyosarcomas (n=9). Carcinoma was the most common SM in metastases (n=20), and most carcinomas were adenocarcinomas (n=12). In metastases, carcinomatous SMs developed after a longer interval from the initial orchiectomy (median times, 213 mo) than sarcomatous SMs (median times, 68 mo). Patients with metastatic SMs had significantly poorer overall survival than those with SMs in the testis (5-y survival rate, 35% vs. 87%; P=0.011). Furthermore, patients with carcinomatous SMs had a significantly worse prognosis than those with sarcomatous or primitive neuroectodermal tumor SMs (5-y survival rates, 17%, 77%, and 73%, respectively; P=0.002), when the whole cohort, including testicular and metastatic SMs, were analyzed. Our results demonstrate that SMs in metastatic GCTs are associated with a significantly worse prognosis than those in the testis. Furthermore, the histologic subtype of SM has a significant effect on the clinical outcome, with the carcinomatous SM carrying the highest risk for mortality.


Subject(s)
Carcinoma/pathology , Neoplasms, Germ Cell and Embryonal/pathology , Neuroectodermal Tumors, Primitive, Peripheral/pathology , Sarcoma/pathology , Testicular Neoplasms/pathology , Wilms Tumor/pathology , Adolescent , Adult , Carcinoma/mortality , Carcinoma/surgery , Humans , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/mortality , Neoplasms, Germ Cell and Embryonal/surgery , Neuroectodermal Tumors, Primitive, Peripheral/mortality , Neuroectodermal Tumors, Primitive, Peripheral/surgery , Orchiectomy , Retrospective Studies , Sarcoma/mortality , Sarcoma/surgery , Testicular Neoplasms/mortality , Testicular Neoplasms/surgery , Wilms Tumor/mortality , Wilms Tumor/surgery , Young Adult
20.
Gynecol Oncol ; 164(2): 304-310, 2022 02.
Article in English | MEDLINE | ID: mdl-34922769

ABSTRACT

BACKGROUND: Despite significant increase in COVID-19 publications, characterization of COVID-19 infection in patients with gynecologic cancer remains limited. Here we present an update of COVID-19 outcomes among people with gynecologic cancer in New York City (NYC) during the initial surge of severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]). METHODS: Data were abstracted from gynecologic oncology patients with COVID-19 infection among 8 NYC area hospital systems between March and June 2020. Multivariable logistic regression was utilized to estimate associations between factors and COVID-19 related hospitalization and mortality. RESULTS: Of 193 patients with gynecologic cancer and COVID-19, the median age at diagnosis was 65.0 years (interquartile range (IQR), 53.0-73.0 years). One hundred six of the 193 patients (54.9%) required hospitalization; among the hospitalized patients, 13 (12.3%) required invasive mechanical ventilation, 39 (36.8%) required ICU admission. Half of the cohort (49.2%) had not received anti-cancer treatment prior to COVID-19 diagnosis. No patients requiring mechanical ventilation survived. Thirty-four of 193 (17.6%) patients died of COVID-19 complications. In multivariable analysis, hospitalization was associated with an age ≥ 65 years (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.11, 4.07), Black race (OR 2.53, CI 1.24, 5.32), performance status ≥2 (OR 3.67, CI 1.25, 13.55) and ≥ 3 comorbidities (OR 2.00, CI 1.05, 3.84). Only former or current history of smoking (OR 2.75, CI 1.21, 6.22) was associated with death due to COVID-19 in multivariable analysis. Administration of cytotoxic chemotherapy within 90 days of COVID-19 diagnosis was not predictive of COVID-19 hospitalization (OR 0.83, CI 0.41, 1.68) or mortality (OR 1.56, CI 0.67, 3.53). CONCLUSIONS: The case fatality rate among patients with gynecologic malignancy with COVID-19 infection was 17.6%. Cancer-directed therapy was not associated with an increased risk of mortality related to COVID-19 infection.


Subject(s)
COVID-19/complications , COVID-19/mortality , Carcinoma/complications , Carcinoma/mortality , Genital Neoplasms, Female/complications , Genital Neoplasms, Female/mortality , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/therapy , Carcinoma/therapy , Female , Genital Neoplasms, Female/therapy , Humans , Logistic Models , Middle Aged , New York City/epidemiology , Patient Acuity , Retrospective Studies , Risk Factors , Treatment Outcome
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