Microsatellite Instability Analysis and Its Prognostic Value in Invasive Nonampullary Duodenal Adenocarcinoma

Abstract Purpose: Nonampullary duodenal adenocarcinoma is a rare disease. Although several prognostic factors have been reported for this disease, they remain controversial due to their rarity. In this study, we retrospectively analyzed 54 cases of invasive nonampullary duodenal adenocarcinoma, focusing on the microsatellite instability phenotype, PD-L1 expression, and prognostic factors. Methods: Expression of the PD-L1 protein and cell differentiation markers in tumors was detected by immunohistochemistry. Microsatellite markers (NR-21, NR-22, NR-24, BAT-25 and BAT-26) were amplified for MSI assessment by PCR.Results: The incidence of microsatellite instability in invasive nonampullary duodenal adenocarcinoma was 35.2%. No significant correlation between the microsatellite instability phenotype and clinicopathological factors was observed. Positive expression of PD-L1 by immune cells was common in advanced-stage disease (P=0.054), and positive expression of PD-L1 in cancer cells correlated significantly with the histologically undifferentiated type (P=0.016). Kaplan-Meier survival analysis demonstrated a significantly better overall survival in patients with microsatellite instability (P=0.013) and at early-stage disease (P=0.000) than in those with microsatellite stability or at late tumor stages. Univariate and multivariate analyses showed that microsatellite instability (hazard ratio [HR]: 0.282, 95% confidence interval [CI]: 0.106-0.751, p=0.011) and early tumor stage (stage Ⅰ-Ⅱ) (hazard ratio [HR]: 8.81, 95% confidence interval [CI]: 2.545-30.500, p=0.001) were independent better prognostic factors of overall survival. Conclusions: Microsatellite instability and early tumor stage (stage Ⅰ-Ⅱ) were independent better prognostic factors of overall survival. A high proportion of microsatellite instability phenotypes and positive PD-L1 expression may be helpful for identifying immune checkpoint inhibitors as a novel therapeutic strategy.

Download Full-text

GATA-3 or T-Bet Expression In PTCL-U Identify High-Risk Patients with Poor Outcomes and Distinct Clinical Characteristics Suggesting Their Derivation From Specific Subsets of T Helper Cells

Blood ◽

10.1182/blood.v116.21.4125.4125 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4125-4125

Author(s):

Ryan A. Wilcox ◽

Andrew L Feldman ◽

Kay Ristow ◽

Thomas M. Habermann ◽

Steven Ziesmer ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

High Risk ◽

Confidence Interval ◽

Median Overall Survival ◽

Performance Status ◽

Univariate Analysis ◽

Tumor Stage ◽

Hazard Ratio ◽

T Helper

Abstract Abstract 4125 Background: With the exception of angioimmunoblastic T-cell lymphomas, which are thought to derive from follicular helper T cells, little is known about the cell of origin for the most common peripheral T-cell lymphoma (PTCL), PTCL-unspecified (PTCL-U). Following appropriate antigenic stimulation, naïve CD4+ T helper (TH) cells differentiate into effector cells that secrete TH cytokines under the transcriptional regulation of subset-specific transcription factors. Methods: PTCL-U patients (n=53) from a single institution were retrospectively identified and immunohistochemical analysis of Foxp3, T-bet and GATA-3 expression performed on diagnostic biopsy specimens. Immunohistochemical staining was reviewed in a blinded fashion by a hematopathologist and all specimens with greater than 10% staining were scored as positive. Transcription factor expression was correlated with patient characteristics and clinical outcomes. Results: GATA-3 expression was observed in 22 (42%) patients, T-bet expression in 17 (32%) patients and Foxp3 expression in 4 (7%) patients. In order to determine the prognostic significance of GATA-3 or T-bet expression, overall survival was compared between patients with GATA-3 (or T-bet) positive or negative tumors. The median overall survival (OS) was 2 years (95% confidence interval 0.7–12.8 years) for patients with GATA-3 negative tumors, compared with a median OS of 0.9 years (95% confidence interval 0.5–1.2 years, p=0.02) for GATA-3 positive cases. The median overall survival was 1.6 years (95% confidence interval 1.0–6.8 years) for patients with T-bet negative tumors, compared with a median overall survival of 0.7 years (95% confidence interval 0.3–0.9 years, p=0.005) for T-bet positive cases. As a subset of tumors coexpressed GATA-3 and T-bet, both of which are adverse prognostic factors, we examined survival outcomes between those patients with tumors expressing either GATA-3 or T-bet (n=29) and those with tumors which do not express either transcription factor (n=24). The median OS and PFS observed for patients with positive tumors was 0.7 years (95% confidence interval 0.6–1.1 years) and 0.7 years (95% confidence interval 0.5–0.9 years), respectively. In contrast, patients with GATA-3/T-bet negative tumors experienced markedly superior survival, with a median OS and PFS of 3.8 years (95% confidence interval 1.6–12.9 years, p<0.0001) and 2.0 years (95% confidence interval 1.5–12.8 years, p<0.0001), respectively. Four-year estimates of overall and progression-free survival were less than 10% for patients with GATA-3/T-bet positive tumors, whereas 4-year OS and PFS were 49% and 32%, respectively, for those with negative tumors. Both GATA-3 and T-bet expression were associated with advanced age and tumor stage. Therefore, we analyzed GATA-3/T-bet expression as a prognostic factor for survival on both univariate and multivariate analyses, adjusting for pertinent risk factors, including patient age and tumor stage. On univariate analysis, GATA-3/T-bet expression was associated with inferior overall survival (hazard ratio 4.4, 95% confidence interval 2.1–10.4, p<0.0001). Patient age (>60 years), poor performance status (ECOG performance status >1), and stage III/IV disease were also associated with inferior overall survival on univariate analysis. However, when adjusting for these latter adverse prognostic factors on multivariate analysis, GATA-3/T-bet expression remained an independent predictor of poor overall survival in PTCL-U (adjusted hazard ratio 3.2, 95% confidence interval 1.4–8.5, p=0.008). Similarly, when adjusting only for high-risk features (>2 adverse prognostic factors), as defined by the Prognostic Index in PTCL-U (PIT), GATA-3/T-bet expression remained an independent predictor of inferior overall survival on multivariate analysis (adjusted hazard ratio 4.9, 95% confidence interval 2.2–11.5, p<0.0001). Conclusions: GATA-3 and T-bet expression identify subsets of high-risk PTCL-U patients who may benefit from alternative treatment strategies. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Prognostic Factors and Clinical Characteristics of Duodenal Adenocarcinoma With Survival: A Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.795891 ◽

2021 ◽

Vol 11 ◽

Author(s):

Huapeng Sun ◽

Yi Liu ◽

Long Lv ◽

Jingwen Li ◽

Xiaofeng Liao ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Lymph Node ◽

Curative Resection ◽

Tumor Resection ◽

Margin Status ◽

High Expression ◽

Duodenal Adenocarcinoma ◽

Gastric Type ◽

Duodenal Carcinoma

BackgroundTo evaluate the clinical risk factors that influence the overall survival in patients with duodenal adenocarcinoma (DA) after tumor resection.MethodsThis study retrospectively analyzed 188 patients who underwent tumor resection for DA between January 2005 and June 2020 at Xiangyang Central Hospital.ResultsThe median survival of the patients who underwent resectional operation was 54 months, longer than of those who underwent palliative surgery (20.8 months) (2,916.17; 95% CI, 916.3−9,280.5; p < 0.001). Survival of non-ampullary duodenal carcinoma patients (50.3 months; 95% CI, 39.7−61.8) was similar to that of ampullary duodenal carcinoma patients (59.3 months; 95% CI, 38.6−66.7) but was significantly better than that of papillary adenocarcinoma patients (38.9 months; 95% CI, 29.8−54.8; p = 0.386). Those with intestinal-type ductal adenocarcinomas had a longer median overall survival than those with the gastric type (61.8 vs. 46.7 months; p < 0.01) or pancreatic type (32.2 months; p < 0.001). Clinical DA samples had significantly diverse expressions of ATG12, IRS2, and IGF2. Higher expressions of the ATG12 and IRS2 proteins were significantly correlated with worse survival. Multivariate Cox regression analysis revealed that lymph node metastasis (hazard ratio (HR), 6.44; 95% CI, 3.68−11.27; p < 0.0001), margin status (HR, 4.94; 95% CI, 2.85−8.54; p < 0.0001), and high expression of ATG12 (HR, 1.89; 95% CI, 1.17−3.06; p = 0.0099) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups with ampullary, non-ampullary, and papillary adenocarcinomas treated with adjuvant chemotherapy (p = 0.973).ConclusionGastric/pancreatic type, high expression of ATG12, lymph node metastases, and margin status were negative prognosticators of survival in patients with DAs than in those with tumor anatomical location. Curative resection is the best treatment option for appropriate patients.

Download Full-text

Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability

Virchows Archiv ◽

10.1007/s00428-007-0444-1 ◽

2007 ◽

Vol 451 (3) ◽

pp. 649-657 ◽

Cited By ~ 63

Author(s):

Fausto Sessa ◽

Daniela Furlan ◽

Clementina Zampatti ◽

Ileana Carnevali ◽

Francesca Franzi ◽

...

Keyword(s):

Prognostic Factors ◽

Microsatellite Instability ◽

Tumor Stage ◽

Tumor Location ◽

Tumor Histology

Download Full-text

Prognostic factors in duodenal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15797 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15797-e15797

Author(s):

Brandon M Huffman ◽

Zhaohui Jin ◽

Cristobal T. Sanhueza ◽

Mindy L. Hartgers ◽

Benny Johnson ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Lymph Node ◽

Tumor Invasion ◽

Univariate Analysis ◽

Prognostic Significance ◽

Clinical Staging ◽

Lymph Node Status ◽

Duodenal Adenocarcinoma

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.

Download Full-text

Prognostic Nomograms for Predicting Overall Survival and Cancer‐Specific Survival of Patients With Malignant Pheochromocytoma and Paraganglioma

Frontiers in Endocrinology ◽

10.3389/fendo.2021.684668 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lei Zheng ◽

Yalong Gu ◽

Jiangcun Silang ◽

Jinlong Wang ◽

Feng Luo ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Univariate Analysis ◽

Roc Curves ◽

Tumor Stage ◽

Malignant Pheochromocytoma ◽

Tumor Type ◽

Lasso Regression ◽

Cancer Specific Survival ◽

Calibration Curves

BackgroundMalignant pheochromocytoma and paraganglioma (PPGL) are rare tumors with few prognostic tools. This study aimed to construct nomograms for predicting 3- and 5-year survival for patients with malignant PPGL.MethodsThe patient data was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 764 patients diagnosed with malignant PPGL from 1975 to 2016 were included in this study. The patients were randomly divided into two cohorts; the training cohort (n = 536) and the validation cohort (n = 228). Univariate analysis, Lasso regression, and multivariate Cox analysis were used to identify independent prognostic factors, which were then utilized to construct survival nomograms. The nomograms were used to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) for patients with malignant PPGL. The prediction accuracy of the nomogram was assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCAs) was used to evaluate the performance of survival models.ResultsAge, gender, tumor type, tumor stage, or surgery were independent prognostic factors for OS in patients with malignant PPGL, while age, tumor stage, or surgery were independent prognostic factors for CSS (P <.05). Based on these factors, we successfully constructed the OS and CSS nomograms. The C-indexes were 0.747 and 0.742 for the OS and CSS nomograms, respectively. In addition, both the calibration curves and ROC curves for the model exhibited reliable performance.ConclusionWe successfully constructed nomograms for predicting the OS and CSS of patients with malignant PPGL. The nomograms could inform personalized clinical management of the patients.

Download Full-text

Non-Hodgkin’s lymphomas of the large bowel - clinical characteristics, prognostic factors and survival

Acta chirurgica iugoslavica ◽

10.2298/aci0803109s ◽

2008 ◽

Vol 55 (3) ◽

pp. 109-114 ◽

Cited By ~ 7

Author(s):

G.Z. Stanojevic ◽

M.P. Stojanovic ◽

M.M. Stojanovic ◽

Z. Krivokapic ◽

M.M. Jovanovic ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Large Bowel ◽

Survival Function ◽

Clinical Information ◽

Tumor Stage ◽

Rank Test ◽

The Difference ◽

Hodgkin's Lymphomas

The aims of this study were to review the clinical presentation of non-Hodgkin?s lymphomas of the large bowel, to analyze the prognostic factors using univariate and multivariate methods, as well as the overall survival. We identified 24 cases at our clinic between 1991 and 2005, based on pathohistological analysis and standard diagnostic criteria established by Dawson et al. They accounted for 1,2% of all cases of the large bowel malignancies (24/2021) during this period. The following clinical information such as age, gender, symptoms, tumor localization, operation performed, histology grade, stage of disease, and adjuvant chemotherapy was obtained. Survival function was expressed by Kaplan-Meier curve and Log-rank test was performed for the difference in survival between two patient groups. Multivariate analysis was carried out using the Cox proportional hazard model. Overall mean survival time was 41,91months. According to the univariete analysis, the factors influencing overall survival rate was operation type (elective and emergent). Tumor stage and operation type were independent prognostic factors for survival, as determined by multivariate analysis. Our results showed that tumor stage and operation type should be considered as the most important prognostic factors in patients with primary non-Hodgkin?s lymphomas of the large bowel.

Download Full-text

Comparison of ADAM19 and CUEDC2 expression in EHCC and their clinicopathological significance

Biomarkers in Medicine ◽

10.2217/bmm-2020-0321 ◽

2020 ◽

Vol 14 (16) ◽

pp. 1573-1584

Author(s):

Shu Xu ◽

Shengfu Huang ◽

Daiqiang Li ◽

Qiong Zou ◽

Yuan Yuan ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Survival Time ◽

Biliary Tract ◽

Extrahepatic Cholangiocarcinoma ◽

Positive Correlation ◽

Overall Survival Time ◽

Positive Expression ◽

Dismal Prognosis ◽

Clinicopathological Significance

Background: To evaluate the expression and clinicopathological significance of a disintegrin and metalloproteinases 19 (ADAM19) CUE domain containing protein 2 (CUEDC2) in extrahepatic cholangiocarcinoma (EHCC). Materials & methods: Immunostaining of ADAM19 and CUEDC2 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues. Result: The expression of ADAM19 and CUEDC2 were significantly higher in EHCC (p < 0.05). ADAM19 expression was positive correlated with CUEDC2 expression in EHCC (p < 0.05). The overall survival time of those with positive expression of ADAM19 and CUEDC2 was lower (p < 0.001). Both positive expression of ADAM19 and CUEDC2 were independent prognostic factors in EHCC. Conclusion: ADAM19 and CUEDC2 have a positive correlation to the pathogenesis and dismal prognosis in EHCC.

Download Full-text

Clinical Characteristics and Prognostic Analysis of Patients With Signet Ring Cell Gastric Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033820983812 ◽

2020 ◽

Vol 19 ◽

pp. 153303382098381

Author(s):

Jia Mi Yu ◽

Zhou Wei Zhan ◽

Jing Xian Zhen ◽

Xiao Jie Wang ◽

Yu Chen ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Adjuvant Chemotherapy ◽

Cell Carcinoma ◽

Gastroesophageal Junction ◽

Tumor Stage ◽

Signet Ring Cell Carcinoma ◽

Signet Ring Cell ◽

Signet Ring ◽

Ring Cell

We do not know the clinical and prognostic factors that influence the survival of patients with gastric signet ring cell carcinoma (SRC). Therefore, a retrospective review was undertaken of 219 patients with SRC who had undergone gastrectomy between January 2009 and December 2012 in our hospital. Patient age, sex, TNM stage, vessel carcinoma embolus, perineural invasion, tumor site and operation type, postoperative chemotherapy, and five-year overall survival were recorded and evaluated. In our study, 93 cases (42.5%) were signet ring cell carcinoma only, and 126 cases (57.5%) were signet ring cell carcinoma coexisting with other components (such as adenocarcinoma or mucus adenocarcinoma). Eighty-three patients were female, 136 were male, 46 occurred at the gastroesophageal junction (21.0%), 63 at the fundus/body (28.8%), 80 were antrum/pylorus (36.5%), and 30 were whole stomach (13.7%). The prognosis of gastric antrum/ pylorus cancer was the best (P < 0.05). There were 133 patients (60.7%) with stage III, and the single factor analysis showed that the earlier the stage, the better the prognosis. The overall five-year survival rate was 30.1% in all patients. One-hundred and 41 patients (64.4%) received D2 radical surgery, 64 (29.2%) received D1 radical operation, and 14 (6.4%) received palliative resection, and the patients who received D2 had the best overall survival (P < 0.05). The survival time of the paclitaxel-based regimen in postoperative adjuvant chemotherapy tended to be prolonged. There was no statistical difference in overall survival between the percentage of signet-ring cells and sex. In summary, age, tumor stage, and surgical resection combined with D2 lymphadenectomy were independent prognostic factors for SRC. Adjuvant chemotherapy with a paclitaxel-based regimen may improve the survival of patients with SRC.

Download Full-text

Prognostic Factors in Penile Cancer: Should We Avoid Inguinal Lymph Node Staging?

Urologia Internationalis ◽

10.1159/000512377 ◽

2021 ◽

pp. 1-5

Author(s):

Luís Vale ◽

Bernardo Fernandes ◽

Vasco Rodrigues ◽

Paulo Dinis ◽

Carlos Silva ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Lymph Node ◽

Confidence Interval ◽

Poor Prognosis ◽

Penile Cancer ◽

Perineural Invasion ◽

Hazard Ratio ◽

Risk Of Death ◽

Inguinal Lymphadenectomy

Introduction: Penile cancer (PC) is a rare neoplasm, mostly in developed countries. Herewith, we evaluate the main prognostic factors of patients with PC undergoing surgery. Methods: This is a retrospective analysis of prognostic factors of overall survival in 65 patients with PC treated at a tertiary referral center over the last 15 years (2004–2018). Results: Almost half (48%) of the patients were diagnosed at an advanced local stage pT3/4. Thirty-eight (58%) patients underwent inguinal lymphadenectomy, and 25 (66%) were negative for lymph node (LN) invasion. Overall survival was 80% at a median follow-up of 31 months. In the multivariate analysis, the main factors of poor prognosis were nodal staging (pN) (p = 0.008) and perineural invasion (p = 0.023). The presence of LN metastasis and perineural invasion in the primary tumor increased the risk of death by 29 (hazard ratio 29.0, 95% confidence interval 2.4–354.2) and 13 (hazard ratio 12.7, 95% confidence interval 1.4–112.0) times, respectively. Discussion/Conclusion: Late diagnosis of PC has a negative impact on overall survival, as nodal invasion correlates with survival. Despite the high number of negative inguinal lymphadenectomy, we continue to advocate aggressive surgical treatment of this disease due to the poor prognosis associated with LN metastasis.

Download Full-text

Nomograms Predict Overall Survival and Cancer-Speciﬁc Survival in Patients with Fibrosarcoma: A SEER-Based Study

Journal of Oncology ◽

10.1155/2020/8284931 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Guang-Heng Xiang ◽

Juan-Juan Zhu ◽

Chen-Rong Ke ◽

Yi-Min Weng ◽

Ming-Qiao Fang ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Tumor Size ◽

Multivariate Analyses ◽

Discrimination Performance ◽

Tumor Stage ◽

Good Discrimination ◽

Cancer Specific Survival ◽

Internal Validation ◽

Clinical Benefits

Purpose. Due to the rarity, it is difficult to predict the survival of patients with fibrosarcoma. This study aimed to apply a nomogram to predict survival outcomes in patients with fibrosarcoma. Methods. A total of 2235 patients with diagnoses of fibrosarcoma were registered in the Surveillance, Epidemiology, and End Results database, of whom 663 patients were eventually enrolled. Univariate and multivariate Cox analyses were used to identify independent prognostic factors. Nomograms were constructed to predict 3-year and 5‐year overall survival and cancer‐specific survival of patients with fibrosarcoma. Results. In univariate and multivariate analyses of OS, age, sex, race, tumor stage, pathologic grade, use of surgery, and tumor size were identiﬁed as independent prognostic factors. Age, sex, tumor stage, pathologic grade, use of surgery, and tumor size were significantly associated with CSS. These characteristics were further included to establish the nomogram for predicting 3-year and 5-year OS and CSS. For the internal validation of the nomogram predictions of OS and CSS, the C-indices were 0.784 and 0.801. Conclusion. We developed the nomograms that estimated 3-year and 5-year OS and CSS. These nomograms not only have good discrimination performance and calibration but also provide patients with better clinical benefits.

Download Full-text