M1 Stage Research Articles

Analysis of the diagnosis and treatment of patients with SMARCB1 (INI-1)-deficient sinonasal carcinoma

Objective: To summarize the clinical features, treatments and outcomes of patients with SMARCB1(INI-1)-deficient sinonasal carcinoma (SDSC). Methods: Fifteen patients who were diagnosed as SDSC in Beijing Tongren Hospital from October 2016 to June 2021 were retrieved, including nine males and six females, ranged from 25 to 78 years old. For TNM stage, one case was in stage T2, one case was in stage T3, 13 cases were in stage T4; 13 cases were in stage N0, two cases were in stage N2; 14 cases were in stage M0, one case was in stage M1. The most common paranasal sinus affected by tumor was the ethmoid sinus. Five patients were treated by radical surgical resection combined with postoperative adjuvant therapy, four patients treated by neoadjuvant therapy with surgical resection, three patients treated by surgical resection only, one patient treated by neoadjuvant therapy with concurrent chemoradiotherapy, one patient treated by preoperative radiotherapy with surgery, and one patient received palliative chemotherapy. Immunohistochemical analysis was performed in all cases. The Kaplan-Meier method was used to draw the survival curve, and the Log-rank test was used to compare the difference to 20 undifferentiated carcinoma patients with positive INI-1 expression in the same period. Results: Immunohistochemical analysis showed the complete absence of INI-1 expression in the tumor nuclei in all 15 cases. The follow-up information was available with a median follow-up time of 21 months (3-56 months). The 3-year overall survival rate, disease specific survival rate, disease-free survival rate and metastasis-free survival rate were 58.9%, 58.9%, 36.4% and 31.2%, respectively. Disease-free survival in SDSC patients was significantly lower compared with undifferentiated carcinoma patients with positive INI-1 expression (HR=2.87,95%CI:0.92~8.91,P=0.043). Cox regression analysis showed that patients with comprehensive treatment based on surgery had a better prognosis than others (HR=8.61,95%CI:1.38~53.73,P=0.021). Conclusion: SDSC is a highly aggressive malignant tumor with the characteristics of easy recurrence, early metastasis and poor prognosis. INI-1 immunohistochemical analysis is recommended in the pathologically poorly differentiated sinonasal carcinoma. Comprehensive treatment based on radical resection may be the first choice for SDSC patients.

Development and validation of a nomogram for predicting the cancer-specific survival of fibrolamellar hepatocellular carcinoma patients.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare subtype of hepatocellular carcinoma. Our study aimed to construct a nomogram to predict the cancer-specific survival (CSS) of FLC. Data of 200 FLC patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) database were divided into the training group and the validation group. Prognostic factors identified in the univariate and multivariate Cox regression analyses were used to construct the nomogram. The concordance index (C-index), calibration curves, time-dependent receiver operating characteristic curve (ROC), and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. As a result, age ≥ 59, N1 stage, M1 stage, tumor size ≤ 2.0cm, and no surgery were significantly associated with lower CSS in multivariate Cox regression analysis. The calibration plot showed good consistency of the nomogram between predicted and observed outcomes in the training and validation groups. Compared with the TNM staging system, the prognostic evaluation model (PEM) showed a higher C-index (0.823 vs 0.656). The PEM also showed better predictive performance, with areas under the curve of 0.909 and 0.890 for predicting the 1- and 5-year survival. The AUCs of the TNM stage model for predicting 1- and 5-year survival were 0.629 and 0.787, respectively. In addition, the DCA curve showed that the nomogram had better clinical utility. Finally, we concluded that Age, N stage, M stage, tumor size, and surgery are independent prognostic factors for FLC. PEM established based on these five prognostic indicators can help predict the CSS of patients with FLC.

Mechanism of crustal thickening and exhumation of southern Lhasa terrane during the Late Cretaceous: Evidence from high-pressure metamorphic rocks of the Eastern Himalayan Syntaxis

AbstractThe mechanism of Late Cretaceous crustal thickening and exhumation of the southern Lhasa terrane is critical for understanding the tectonic evolution of the Tibetan Plateau. High-pressure metamorphic rocks from the lower crust are good candidates for addressing this issue. In this study, we focus on Late Cretaceous, high-pressure, garnet-bearing amphibolites from the Nyingchi Complex of the Eastern Himalayan Syntaxis and present an integrated study of geochronology, petrography, mineral chemistry, and thermodynamic modeling. Petrographic data determine three metamorphic stages (M1–M3). The M1 stage is characterized by a peak mineral assemblage of garnet + hornblende + albite + rutile + muscovite + quartz, which is followed by a post-peak (M2) assemblage of garnet + hornblende + plagioclase + epidote + biotite + rutile + quartz. The late retrograde stage (M3) is defined by hornblende + plagioclase symplectites surrounding garnet porphyroblasts. Mineral chemistry, with thermodynamic modeling, constrains the P-T conditions of the M1–M3 stages to 14–19 kbar/660–720 °C, 8–10 kbar/650–660 °C, and <7 kbar/<600 °C, respectively. Metamorphic zircons yield a concordant age at 90 Ma, which indicates the formation of garnet-bearing amphibolites. These results indicate a P-T-t path involving near-isothermal decompression for garnetbearing amphibolites, which suggests that the Nyingchi Complex underwent peak-pressure metamorphism (M1) at 90 Ma, followed by rapid exhumation to the depth of 32–26 km along the subduction channel. Moreover, the garnet-bearing amphibolites are considered to be the product of high-pressure metamorphism of mafic crust at the base of the Gangdese belt. Hence, the crust of the Gangdese belt experienced significant crustal thickening of up to 60 km at 90 Ma.

Diagnostic Value of Spiral CT and Magnetic Resonance Imaging Scanning in Gastric Cancer and Precancerous Lesions.

In order to explore the diagnostic value of spiral CT and magnetic resonance imaging scanning in gastric cancer and precancerous lesions, the author selected 56 gastric cancer patients treated in a medical center (group) as the experimental subjects, and all patients underwent MRI, multislice spiral CT scan, and enhanced CT scan two weeks before surgery; at the same time, the gastric cancer staging results of patients were diagnosed according to surgical pathology. All patients were examined under the condition of knowledge and performed breath-holding exercise before examination. The status, location, and extent of tumor lesions were evaluated. In comparison of T staging of gastric cancer patients with magnetic resonance scanning imaging and postoperative pathological examination results, among them, T staging of 3 patients did not match the results of pathological examination, the accuracy rates of T staging on magnetic resonance scanning imaging were T1 = 94.7%, T2 = 87.6%, T3 = 91.2%, and T4 = 94.7%, and the total accuracy was 92.1%. Comparison of helical CT scan imaging and postoperative pathological examination results is as follows. Among them, T staging of 8 patients did not match the results of pathological examination, 3 patients were ulcerative, 5 were protuberance, the accuracy rates of T staging in spiral CT scan imaging were T1 = 90.8%, T2 = 82.2%, T3 = 76.9%, and T4 = 87.6%, and the total accuracy was 84.5%. The total accuracy rate of imaging N staging was 77.5%, and the total accuracy rate of spiral CT scanning imaging N staging was 80.8%. The accuracy rates of M0 and M1 staging in magnetic resonance imaging were 100.0% and 96.5%, respectively, and the accuracy rates of M0 and M1 staging in spiral CT scan imaging were 96.5% and 96.5%, respectively. The accuracy rate of magnetic resonance imaging for the diagnosis of gastric cancer N staging was 77.4%, and the reason for the low accuracy rate was mainly because the enhancement effect was not obvious due to insufficient enhancement. The accuracy rate of spiral CT in diagnosing N staging of gastric cancer was 80.9%, which was mainly due to the small diameter of the middle celiac artery lymph nodes. Magnetic resonance and spiral CT scans have high value in the early diagnosis and staging of gastric cancer.

Association of multiple tumor markers with newly diagnosed gastric cancer patients: a retrospective study.

BackgroundThe purpose of this paper was to explore the correlation between multiple tumor markers and newly diagnosed gastric cancer.MethodsWe selected 268 newly diagnosed patients with gastric cancer and 209 healthy subjects for correlation research. The detection of multiple tumor markers was based on protein chips and the results were statistically analyzed using SPSS.ResultsWe concluded that gastric cancer was significantly related to gender, age, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and carbohydrate antigen 242 (CA242) positive levels (P < 0.001). After CA199 and CA242 were stratified by gender, the male odds ratio (OR) was 30.400 and 31.242, respectively, while the female OR was 3.424. After CA125 was stratified by age in patients over 54 years old with gastric cancer, the risk of occurrence in the CA125-positive population was 16.673 times that of the CA125-negative patients. Among patients 54 years old and younger, being CA125-positive was not a risk factor for gastric cancer (P = 0.082). AFP, CEA, CA125, CA199, and CA242 positive levels during the M1 stage were statistically significant when compared with the M0 stage and control group (P < 0.001), but the AFP (P = 0.045) and CA125 (P = 0.752) positive levels were not statistically significant when compared with the M0 stage and control group. The combined detection sensitivity of multiple tumor markers was 44.78%.ConclusionOur research shows that gastric cancer is associated with age, gender, and the positive levels of AFP, CEA, CA125, CA199, and CA242. The positive levels of AFP and CA125 were related to the distant metastasis of gastric cancer. To a certain extent, the combined detection sensitivity can be used for the initial screening of gastric cancer.

A nonendemic analysis of the patterns and prognosis of de novo metastatic nasopharyngeal carcinomas in older patients aged ≥ 65 years

This study aimed to investigate the prognostic factors related to overall survival (OS) and cancer-specific survival (CSS) in patients with de novo metastatic nasopharyngeal carcinoma (NPC) aged ≥ 65 years in nonendemic areas. The Surveillance, Epidemiology, and End Results database was queried for elderly patients with M1 stage NPC at initial diagnosis between 2004 and 2016. This study examined 100 patients and evaluated the relationship of sex, age, race, pathological grade, T stage, N stage, sequence number, site of metastasis, number of metastatic organs, and other related factors with OS and CSS. The median survival and follow-up time were 10 and 48 months, respectively. The survival curves for race, bone metastasis, radiation, and chemotherapy significantly affected OS on the log-rank test. Advanced N stage and liver metastasis may be associated with poor survival. Race, bone metastasis, and chemotherapy were independent prognostic factors of OS. Bone metastasis was associated with poor survival. The survival curves for CSS were significantly different between races, N stage, sequence number, and bone metastasis. In Cox regression multivariate analysis, only sequence number had an independent effect on prognosis. This study revealed that chemotherapy prolonged survival in elderly patients with metastatic NPC, whereas bone metastasis shortened survival.

PD46-04 BRCA1/2 AND ATM MUTATED METASTATIC PROSTATE CANCERS MAY PRESENT WITH LOW SERUM PSA

You have accessJournal of UrologyCME1 May 2022PD46-04 BRCA1/2 AND ATM MUTATED METASTATIC PROSTATE CANCERS MAY PRESENT WITH LOW SERUM PSA Hyunho Han, Cheol Keun Park, Nam Hoon Cho, Jong Su Lee, Won Sik Ham, Woong Kyu Han, and Young Deuk Choi Hyunho HanHyunho Han More articles by this author , Cheol Keun ParkCheol Keun Park More articles by this author , Nam Hoon ChoNam Hoon Cho More articles by this author , Jong Su LeeJong Su Lee More articles by this author , Won Sik HamWon Sik Ham More articles by this author , Woong Kyu HanWoong Kyu Han More articles by this author , and Young Deuk ChoiYoung Deuk Choi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002614.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PARP inhibitors have shown survival benefits in M-CRPC patients with homologous recombination repair (HRR) genes (BRCA1/2, and ATM) mutations. Germline panel test of the HRR genes and tumor tissue next generation sequencing (NGS) are recommended in men with metastatic prostate cancer. The reported incidences of BRCA1,2 and ATM gene mutations are 5-10%, yet it is unclear whether the mutations are enriched in advanced cancer and associated with clinical features. We assessed the incidences and clinical characteristics of HRR genes BRCA1/2 and ATM mutated prostate cancer. METHODS: Our institute has incorporated prostate cancer tissue NGS in clinical practice since Jun 2019. Indications include prostate cancer of high risk (GGG4-5, cT3/4, N1 or M1). Trusight oncology 170/500 panels were used. We assessed the incidences of BRCA1/2 and ATM mutations (including variant of unknown significance) in the tested population. Clinical characteristics of HRR mutated tumors and wild-type tumors were compared. T-test (two-sided) with Welch’s correction was used. RESULTS: We evaluated 126 consecutive prostate cancer tissue NGS data (from Jun 2019 and April 2021). At the time of diagnosis, cT3/4, N1 and M1 stages were 107(85%), 54(43%) and 35(28%) samples, respectively. BRCA1/2 and ATM mutation frequencies were similar across the stages: 32% at T2 vs 34% at T3/4; 35% at N0 vs 31% at N1; 32% at M0 vs 37% at M1. HRR mutations tended to be more frequent in GGG 5 than GGG1-4 (41% vs 28%, p = 0.15). Of metastatic subgroup (N1 or M1, n=62), mean PSA at the time of diagnosis was significantly lower in HRR mutated tumors than wild-type (82ng/mL vs 561ng/mL, p = 0.02). Similar trend was noted in a M-CRPC public dataset (188ng/mL vs 76ng/mL, p = 0.09) (Abida et al., PNAS, 2019). In localized subgroup (N0 and M0, n=64), PSA was not significantly different (58ng/mL vs 26ng/mL, p=0.30). CONCLUSIONS: BRCA1/2 and ATM mutated metastatic prostate cancers may present with low serum PSA. Source of Funding: NA © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e789 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hyunho Han More articles by this author Cheol Keun Park More articles by this author Nam Hoon Cho More articles by this author Jong Su Lee More articles by this author Won Sik Ham More articles by this author Woong Kyu Han More articles by this author Young Deuk Choi More articles by this author Expand All Advertisement PDF DownloadLoading ...

Adoption of Two-Dimensional Ultrasound Gastrointestinal Filling Contrast on Artificial Intelligence Algorithm in Clinical Diagnosis of Gastric Cancer.

This research was aimed to explore the value of gastrointestinal filling contrast-enhanced ultrasound (CEUS) and computed tomography (CT-)-enhanced scanning based on artificial intelligence (AI) algorithm in the evaluation of gastric cancer staging. 102 patients with gastric cancer were selected as the research objects. All of them underwent CEUS of gastrointestinal filling and 64-slice spiral CT before surgery. In addition, an improved mean shift algorithm was proposed based on differential optical flow and deep convolutional neural network (D-CNN), which was applied in image processing. The predicted positive rate (PPR), sensitivity, specificity, and accuracy of gastric cancer in different stages by CEUS and CT were calculated using pathological diagnosis results as the gold standard. 17 patients with T1 stage, 41 patients with T2-T3 stage, and 35 patients with T4 stage were detected by CEUS. 13 patients with T1 stage, 34 patients with T2-T3 stage, and 30 patients with T4 stage were detected by CT enhanced examination. The PPRs of CEUS for T1, T2-T3, and T4 stages of gastric cancer were higher than those of CT enhanced (P < 0.05). The PPR of CEUS for N0 staging of gastric cancer was higher than that of CT enhanced (P < 0.05), and it for N3 staging of gastric cancer was lower than that of CT enhanced (P < 0.05). From the analysis of M staging of gastric cancer, the PPRs of CEUS for M0 and M1 staging of gastric cancer were not statistically different from the PPRs of CT enhanced (P > 0.05). The sensitivity (95.6%), specificity (81.82%), and accuracy (94.12%) of CEUS in assessing resectability were significantly higher than those of CT enhancement (89.01%, 63.67%, and 86.27%, respectively), and the differences were statistically significant (P < 0.05). In summary, CEUS gastrointestinal filling based on the D-CNN algorithm could better improve the display rate of the tissue lesions around the stomach. It also helped to judge the lesion progress, the depth of infiltration, and lymph node metastasis of the lesion. In addition, it had excellent performance in evaluating the resectability of gastric cancer before surgery and had clinical promotion value.

Prognostic nomograms to predict overall survival and cause specific death in vulvar squamous cell carcinoma

ObjectiveThe incidence of vulvar squamous cell carcinoma has been rising in recent decades. The prognosis of patients with vulvar squamous cell carcinoma was explored, and nomograms were constructed to predict...

Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio on low-grade appendiceal mucinous neoplasm: A single tertiary hospital experience.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare disease, which prognostic factors were difficult to evaluate. Inflammation markers, like neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), were used as prognosticators for various cancers. This study aimed to investigate the prognostic value of pretreatment NLR and PLR on LAMN. From January 2000 to September 2018, there were 57 patients diagnosed with LAMN in Taipei Veterans General Hospital. Patients diagnosed with mucinous cystadenoma, mucinous tumor with uncertain malignant potential before 2010 were also included based on previous classification. Clinical and pathological data were collected. Patients were separated into high-NLR (NLR-H) and low-NLR (NLR-L) groups according to cutoff value of 3. Similarly, they were separated into high-PLR (PLR-H), and low-PLR (PLR-L) groups with cutoff value of 300. Overall survival (OS) and recurrence-free survival (RFS) were analyzed. Among all patients, the median follow-up time was 42 months. Age, gender, clinical manifestations, type of surgery, and T stage were similar in different NLR and PLR groups. Both NLR-H and PLR-H groups had higher rate of M1 stage of diseases (22.7% vs 9.4%, p = 0.04; 57.1% vs 8.8%, p < 0.01, respectively). PLR-H group had more presence of pseudomyxoma peritonei (PMP) (57.1% vs 15.2%, p = 0.03). In univariate analysis, factors such as age, gender, tumor perforation, and operation did not have impact on OS nor RFS. On the other hand, M1b stage is the only significantly poor prognostic factor on RFS (hazard ratio, 57.96, 95% CI, 5.16-651.23, p < 0.01). Both NLR-H and PLR-H had more M1 stage of diseases, but they were not correlated to OS nor RFS. PLR-H group had higher rate of presence PMP. Nevertheless, patients with LAMN and cellular PMP (M1b stage) had a higher rate of recurrence, and other factors showed no statistical difference in OS nor RFS.

Myoepithelial carcinoma of major salivary glands: Analysis of population-based clinicopathologic and prognostic features

BackgroundThis study aimed to investigate the effect of demographic characteristics and disease stage on the survival outcomes of patients with myoepithelial carcinoma (MECA) of the salivary glands, and to assess the role of radiotherapy in these patients. MethodsThe Epidemiology, Surveillance and End Results database was queried from 2000 to 2018 to identify patients with MECA. Data pertaining to the tumor stage, size, histological grade, and demographic characteristics were analyzed. The relationship between clinicopathological features and overall survival (OS) was assessed using statistical analyses. ResultsIn total, 290 patients (137 men and 153 women) were identified. The parotid gland was the most common tumor location (76.6% patients). Approximately half of the patients had locally advanced tumors, and 14.5 and 6.6% had lymph node and distant organ involvement, respectively. The median OS was 142 months, while the survival rates at 120 months and 180 months were 53% and 39%, respectively. In the cohort, 160 patients (55.2%) underwent surgery alone, while 130 patients (44.8%) underwent surgery combined with radiotherapy. Multivariate Cox analysis revealed that histopathological grade, stage, T3 stage (hazard ratio [HR]: 2.47, P = 0.039), T4 stage (HR: 3.33, P = 0.011), N2 stage (HR: 6.59, P = 0.002), and M1 stage (HR: 2.72, 95%confidence interval [CI]: 1.03–7.19; P = 0.044) were associated with poor prognosis. Radiotherapy (HR: 0.58, P = 0.042) was a favorable factor for OS, and it reduced the mortality risk by 42%. ConclusionsHistological grade, stage, and radiotherapy are independent risk factors for OS. The decision to administer chemotherapy for MECA should be made with caution. Adjuvant radiotherapy is recommended in high-risk patients.

Comparison of prognostic factors of esophageal cancer between a Chinese cohort and the Surveillance, Epidemiology, and End Results (SEER) database: a retrospective cohort study.

Esophageal cancer is a highly aggressive, early metastasis gastrointestinal malignancy, with geographic differences in prognosis. It is unknown whether there are differences in the survival in different regions among esophageal cancer patients who underwent the treatments. This study was to explore the influencing factors of esophageal cancer survival in patients from China and the Surveillance, Epidemiology, and End Results (SEER) database. The retrospective cohort study were conducted with 605 Chinese esophageal cancer patients in the Wuxi People's Hospital and 2,351 patients from the SEER database. The demographic and clinical data were collected from the two cohort, respectively. The outcome was the death during the follow-up. The follow-up ended on November 30, 2021. The Cox proportional hazards model was used in the univariate and multivariate survival analyses, with hazard ratio (HR) and 95% confidence interval (CI). In group one, the following were identified as the prognostic factors: female gender (HR =0.568; 95% CI: 0.398-0.811), T3 and T4 stages (HR =3.312; 95% CI: 2.493-4.401), N2 and N3 stages (HR =3.562; 95% CI: 2.631-4.824), and other subtypes of cancer (HR =0.393; 95% CI: 0.223-0.693). The following prognostic were factors identified in group two: age ≥65 years (HR =1.16; 95% CI: 1.058-1.276), female gender (HR =0.843; 95% CI: 0.752-0.945), T3 and T4 stages (HR =1.523; 95% CI: 1.373-1.690), M1 stage (HR =2.554; 95% CI: 2.303-2.832), treatment with surgery and chemotherapy (HR =0.507; 95% CI: 0.457-0.562), and other subtypes of cancer (HR =1.432; 95% CI: 1.298-1.581). There may be some differences in prognostic factors between Chinese and American patients with esophageal cancer. It is indicated that different management strategies of esophageal cancer should be considered in different populations to improve the prognosis of patients.

Prostate Cancer Disparities in Hispanics Using the National Cancer Database

ObjectivesTo evaluate the differences in prostate cancer characteristics and treatment between Hispanic Americans with different countries of origin using the National Cancer Database. MethodsWe performed a retrospective analysis of 54,947 adult Hispanic Americans diagnosed with prostate cancer between 2004 and 2015. Origin was Mexican (N = 7844; 14.3%), South/Central American (N = 4010; 7.3%), Puerto Rican (N = 2938; 5.4%), Cuban (N = 2549; 4.6%), Dominican (N = 1535; 2.8%), Hispanic not specified (N = 36,269; 65.7%). Comparison between characteristics among Hispanic American sub-groups’ categories was performed using chi-square and Kruskal-Wallis tests for categorical and continuous variables respectively. ResultsMexicans had overall worse disease at presentation including highest median PSA (7.8 ng/mL), most prevalent T3/T4 stage (6.7%), M1 stage (8.9%), and high-grade Gleason scores (24.0%) when compared to all other Hispanic American groups. Cubans were most likely to receive hormone therapy and radiation therapy and least likely to receive surgical treatment. Compared to Mexicans, Cubans (hazards ratio [HR] = 1.30, 95% confidence interval = [1.16-1.44]) had worse overall survival, while Puerto Ricans (HR = 1.08 [0.95-1.19] had similar overall survival, and Dominicans (HR = 0.63 [0 0.53-0.75]), South/Central Americans (HR = 0.75, [0.66-0.84]) and not specified (HR = 0.84 [0.79-0.91]) had better survival. ConclusionAmong Hispanic Americans with different countries of origin, disparities in prostate cancer characteristics, treatment choice, and survival do exist. Mexicans had the least favorable prostate cancer characteristics at presentation. Cubans had the worst overall survival while they were also most likely to receive hormone and/or radiation as first-line treatment. Our analysis demonstrates significant heterogeneity in the Hispanic American population.

Intraperitoneal perforation through lymph node metastases in a patient with esophageal squamous cell carcinoma during intensive chemotherapy: A case report with literature review.

IntroductionEsophageal fistula after treatment is a critical and fatal complication of esophageal cancer. A fistula forming from lower thoracic esophageal cancer to the peritoneum through lymph node metastases following chemotherapy has not been reported. We report a case of peritonitis due to lymph node perforation through the tumor ulcer after induction of biweekly docetaxel, cisplatin, and 5FU combined chemotherapy (Bi-DCF) for advanced esophageal squamous cell carcinoma (ESCC).Presentation of caseA 48-year-old woman was referred to us with a diagnosis of lower thoracic ESCC and thoracoabdominal aortic aneurysm. Esophagogastroduodenoscopy showed a circumferential type 3 tumor with stenosis in the lower thoracic esophagus. Contrast-enhanced computed tomography (CT) showed a thoracoabdominal aortic aneurysm and wall thickening of the lower thoracic esophagus that was suspicious of esophageal cancer. Lymph node metastases dumpling from around the tumor to abdominal cavity were also observed. The initial diagnosis was ESCC T3 N3 M1 (para-aortic lymph nodes and liver) Stage IVB. She was started on Bi-DCF (docetaxel 35 mg/m2 days 1/15, cisplatin 40 mg/m2 days 1/15, 5FU 400 mg/m2 days 1–5, 15–19) as the first-line regimen. The third day after starting chemotherapy, she felt strong abdominal pain, and internal necrosis of lymph nodes around the primary lesion and free air in the abdominal cavity were found. Peritonitis was diagnosed due to a fistula formed from the lower thoracic ESCC to the peritoneum through lymph node metastases. She underwent emergency laparoscopic drainage, omental filling, and jejunostomy. Postoperatively, her general condition and inflammatory findings improved within 10 days, and she could continue intensive chemotherapy as scheduled.DiscussionBecause of the risk of perforation and fistula in regimens that are expected to cause tumor shrinkage, careful observation may be required after starting chemotherapy.ConclusionWe report the first case of peritonitis caused by perforation through lymph node metastasis of thoracic esophageal cancer.

Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.

Value of UGT2B7-161 Single Nucleotide Polymorphism in Predicting the Risk of Cardiotoxicity in HER-2 Positive Breast Cancer Patients Who Underwent Pertuzumab Combined with Trastuzumab Therapy by PSL.

ObjectiveTo explore the value of uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7)-161 single nucleotide polymorphism in predicting the occurrence of cardiotoxicity in Chinese human epidermal growth factor 2 (HER-2) positive breast cancer patients who underwent pertuzumab combined with trastuzumab Therapy.MethodsFifty patients with HER-2 positive breast cancer who planned to receive trastuzumab and pertuzumab therapy for more than four cycles were enrolled in this study, and blood samples were collected. Thirty healthy volunteers of matching ages were selected as the control group. Myocardial parameters such as global work index, global effective work, and global wasted work were measured before treatment (M0) and at the end of four cycles of treatment month three (M3). Blood samples were collected from patients at the M0 stage, and polymorphisms of the UGT2B7-161 gene were detected to evaluate the predictive ability of different gene phenotypes on the myocardial drug toxicity injury.ResultsThere were 35 myocardial work decreased events among 50 patients. There were 24 (47.3%), 15 (40.8%), and 11 (11.8%) patients carrying UGT2B7-161 CC, CT, and TT genotypes, respectively. The occurrence of myocardial work decreased was decreased in UGT2B7-161 TT and CT genotypes (12.5%) compared with CC genotype (41.7%) with statistical significance (P < 0.001). Multivariate logistic regression model analysis exhibited that UGT2B7-161 genotypes, body mass index, and cardiac troponin I were independent factors influencing the risk of cardiotoxicity.ConclusionUGT2B7-161 single nucleotide polymorphism is a potential predictive factor for cardiotoxicity in HER-2 positive breast cancer patients receiving trastuzumab and pertuzumab dual-targeted drug therapy.

Targeting the Macrophage: Immune Cells May Be the Key to Phthalate-Induced Liver Toxicity.

Targeting the Macrophage: Immune Cells May Be the Key to Phthalate-Induced Liver Toxicity.

Neoproterozoic Eclogite-to Granulite-Facies Transition in the Ubendian Belt, Tanzania, and the Timescale of Continental Collision

AbstractIn collision-type orogens, where high-pressure and ultrahigh-pressure (HP–UHP) metamorphism usually occurs, deeply subducted continental slabs with eclogitized mafic rocks often undergo recrystallization/overprinting with various geothermal gradients after the peak conditions at lower-to-middle-crustal levels. During the crustal stabilization, the transition from eclogite-to granulite-facies is common. We conducted metamorphic petrology and zircon geochronology on (1) bimineralic and (2) partially granulitized eclogites from the Neoproterozoic Ufipa Terrane (Southwestern Tanzania). Microtextural relationships and mineral chemistry define three metamorphic stages: eclogite metamorphism (M1), HP granulite-facies overprinting (M2), and amphibolite-facies retrogression (M3). The bimineralic eclogite has a basaltic composition and lacks M2 minerals. In contrast, the kyanite eclogite is characterized by a gabbro-dioritic whole-rock composition and contains inherited magmatic zircon. Although the matrix is highly granulitized, garnet and kyanite contain eclogite-facies mineral inclusions. Phase equilibria modeling revealed P–T conditions of 2.1–2.6 GPa and 650–860°C for the M1 stage and 1.4–1.6 GPa and 750–940°C for the M2 stage. Zircon with eclogite-facies mineral inclusions from the bimineralic eclogite lacks Eu anomaly in the REE patterns and yielded the M1 eclogite metamorphic age of 588 ± 3 Ma. Zircon overgrowths surrounding the inherited Paleoproterozoic magmatic cores in kyanite eclogite yielded 562 ± 3 Ma. A weak negative Eu anomaly in the REE patterns and the absence of eclogitic mineral inclusions suggest the zircon growths at the M2 HP granulite-facies metamorphic stage. These new data indicate an eclogite-to granulite-facies transition time of 26 ± 4 million years (Myr), suggesting a rate of HP rock exhumation toward a lower crustal level of 0.7–1.5 mm/year. Furthermore, the density evolution model indicates that buoyant host orthogneiss with low-density gabbro-dioritic eclogite plays an important role in carrying high-density basaltic eclogite. Our 2D thermomechanical modeling also suggests that a slab break-off with a lower angle subduction of &amp;lt;20° triggers the exhumation of the HP slab sliver with 20–30 Myr eclogite-to granulite transition time of large HP–UHP terranes in major collision zones.

Disparities in prostate cancer: An ethnicity comparative focus among Hispanic Americans versus non-Hispanic whites.

23 Background: Prostate cancer (PCa) is a clinically heterogeneous disease and the incidence and mortality risk varies widely among racial/ethnic groups. Among Hispanic American (HA) men, PCa accounts for nearly one-quarter of the total cancer burden; in addition, advanced stage and mortality rates are significantly higher in HA compared to Non-Hispanic White (NHW) men. Despite a decade of declining overall incidence rates, incidence rates of advanced PCa appear to be increasing over time among HA men, a similar pattern seen among Non-Hispanic Blacks (NHB). Methods: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA at diagnosis between 2010 and 2016. HAs were divided into four major subgroups: Mexican/Chicano, Puerto Ricans, Cubans, and Central/South Americans. NHB, Asian, and other racial groups were excluded. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Univariable and multivariable logistic regression models were used to evaluate the association of HA ethnic subgroups with metastatic presentation and primary treatment. Results: A total of 428,829 patients were included with 5,625 (1.3%) being HA. Mexican comprised 51.2% of HAs and presented with higher PSA and Gleason score at diagnosis and more advanced cT, N1 and M1 stage when compared to NHW men and other HA subgroups (all, p &lt; 0.001) (Table). After adjusting for age, PSA, year of diagnosis, cT, N, insurance, income, education, and performance score, Mexican had 1.32 (95%CI: 1.07-1.63, p = 0.01) higher odds of initial metastatic presentation and 0.68 (95%CI: 0.55-0.85, p &lt; 0.001) lower odds of receiving treatment compared to NHW men while no statistically significant difference was seen for the other HA subgroups. Conclusions: Even after accounting for socioeconomic disparities, Mexican men present with a more aggressive disease when compared to NHW and other HA subgroups. Our results warrant further investigations into potential biological factors affecting HA PCa as well as identifications of potential barriers to treatment for vulnerable populations.[Table: see text]

Abstract OT1-02-03: Trastuzumab deruxtecan (T-DXd; DS-8201) vs trastuzumab emtansine (T-DM1) in high-risk patients with HER2-positive, residual invasive early breast cancer after neoadjuvant therapy: A randomized, phase 3 trial (DESTINY-Breast05)

Abstract Background Preoperative chemotherapy in combination with trastuzumab and pertuzumab is a preferred regimen for treating patients (pts) with HER2-positive, invasive, early breast cancer (BC). Pts who have received such treatment but still have residual invasive disease in the breast or lymph nodes at surgery are at greater risk for disease recurrence or death than those with a pathological complete response. The antibody-drug conjugate (ADC) T-DM1 is approved as a postneoadjuvant treatment for pts with residual invasive disease (in the breast and/or axillary nodes) after optimal neoadjuvant chemotherapy and trastuzumab (or trastuzumab with pertuzumab). T-DXd is a potent HER2-targeted ADC with a humanized HER2 antibody attached to a membrane-permeable topoisomerase I inhibitor payload by a cleavable tetrapeptide-based linker and a drug-to-antibody ratio of ≈8. T-DXd is approved globally for the treatment of adult pts with HER2-positive, unresectable or metastatic BC who have received ≥2 prior anti-HER2-based regimens in the metastatic setting or had prior chemotherapy and are refractory to or intolerant of standard treatments. These approvals have been supported by results from DESTINY-Breast01, an open-label, international, multicenter, phase 2 study of T-DXd in patients with HER2-positive metastatic BC. In an updated data cutoff (June 8, 2020), T-DXd demonstrated an objective response rate (ORR) of 61.4% (113/184 pts) and a duration of response of 20.8 months in pts with HER2-positive (IHC 3+ or ISH+), unresectable or metastatic BC previously treated with T-DM1 (Modi et al. Cancer Res. 2021;81[4 suppl]:PD3-06). Yet, further unmet need exists in patients who do not achieve pathologic complete response to neoadjuvant treatment, as these patients have increased risk of recurrence. Here, we describe a randomized phase 3 trial evaluating T-DXd vs T-DM1 as postneoadjuvant treatment for high-risk pts with HER2-positive primary BC who have residual invasive disease following neoadjuvant therapy. Study Description DESTINY-Breast05 is a multicenter, open-label, randomized, phase 3 trial comparing the efficacy and safety of T-DXd with those of T-DM1 in pts with HER2-positive (IHC 3+ or ISH+, centrally confirmed on pretreatment biopsy), invasive BC with pathologic evidence of residual invasive disease in the breast or axillary lymph nodes after neoadjuvant therapy. Additionally, pts must have a higher residual risk for recurrence, following standard T-DM1, defined as either presenting with inoperable disease (clinical stages T4, N0-3, M0 or T1-3, N2-3, M0) or operable BC at presentation (clinical stages T1-3, N0-1, M0) with axillary node-positive disease after neoadjuvant chemotherapy and anti-HER2 treatment. Approximately 1600 pts will be randomly assigned (1:1) to T-DXd or T-DM1 from ≈ 400 sites globally. Randomization is stratified by operative status at presentation, hormone receptor status, pathologic nodal status following neoadjuvant therapy, and type of HER2-targeted neoadjuvant therapy (single vs dual). T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg will be administered intravenously once every 3 weeks for 14 cycles. Invasive disease-free survival based on investigator assessment is the primary efficacy endpoint. Secondary endpoints are overall survival, disease-free survival, distant recurrence-free interval, and brain metastasis-free interval. The pharmacokinetics of T-DXd, biomarkers, and health-related quality of life will also be evaluated (NCT04622319). Citation Format: Charles E Geyer, Jr, Michael Untch, Aleix Prat, Priya Rastogi, Naoki Niikura, Elton Mathias, Lee Anne McLean, Yibin Wang, Sibylle Loibl. Trastuzumab deruxtecan (T-DXd; DS-8201) vs trastuzumab emtansine (T-DM1) in high-risk patients with HER2-positive, residual invasive early breast cancer after neoadjuvant therapy: A randomized, phase 3 trial (DESTINY-Breast05) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-02-03.