Non-metastatic Adenocarcinomas Research Articles

Analysis of survival and prognostic factors in appendix adenocarcinoma and mucinous carcinoma.

This study aimed to compare mucinous carcinoma and adenocarcinoma of the appendix in terms of survival and investigate the risk factors influencing survival. The data for this study were retrieved from the SEER database (SEER Research Plus 17 registries). Patients diagnosed with appendix cancer between 2004 and 2019 were included. Demographic data, such as age, gender, marital status, and year of diagnosis, along with oncological variables like stage, surgery, chemotherapy, radiotherapy, and survival time, were extracted from the SEER database. Pathological subtypes were classified as adenocarcinoma (AC) and mucinous adenocarcinoma (MAC) based on the College of American Pathologists guidelines. Patients with other pathological subtypes or missing data were excluded from the study. This study included 4524 patients, with 2118 (46.8%) classified as AC and 2406 (53.2%) as MAC. There was no significant difference in mean age between AC and MAC groups (63.22 ± 14.30 vs. 59.46 ± 14.07, p = 0.483). AC was more common in males, while MAC was more prevalent in females (46.8% vs. 53.2%; 55.6% vs. 44.4%, p < 0.001, respectively). Married status was high in both groups (p = 0.001). While no difference was found in white race distribution, the black race was more prevalent in the AC group (57.1% vs. 42.9%, p < 0.001). Grade 1 tumors were more frequent in the AC group, whereas Grades 2 and 3 were more common in the MAC group (p < 0.001). Stages 1, 2, and 3 were more prevalent in the AC group, while the majority of MAC cases were at Stage 4. Surgery rates were higher in the AC group (98.6% vs. 96.4%, p < 0.001). Chemotherapy was used more frequently in the MAC group (50.9% vs. 40.6%, p < 0.001), while radiotherapy rates were similar in both groups (p = 0.498). The mean follow-up period was 55.70 ± 47.2months. Five- and ten-year survival rates for the MAC group were 64.4% and 50.2%, respectively, higher than the AC group's rates of 54.2% and 39.7% (p < 0.001). The overall risk of mortality was 1.4 times higher in the AC group compared to the MAC group (p < 0.001, HR: 1.377 [CI 95% 1.259-1.507]). While adenocarcinomas and mucinous adenocarcinomas have similar incidences, non-metastatic adenocarcinomas were more frequently observed. In contrast, mucinous adenocarcinomas often exhibited distant metastases. Nevertheless, the survival rate was higher in mucinous adenocarcinomas.

Predictors of Recurrence in Nonmetastatic Appendiceal Epithelial Cancers: An Updated Single-Center Experience Over 25 Years.

Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas. Patients with nonmetastatic appendiceal adenocarcinoma at a single institution from 1994 to 2020 were included. Clinicopathologic characteristics that predict recurrence and lymph node metastasis were analyzed. Workup included staging laparoscopy with right hemicolectomy, seriel imaging and biochemical monitoring. A total of 147 patients with mAC (18%), cAC (22%), and GCAs (59%) were included. After median follow-up of 53 months, 23 (16%) patients recurred, most commonly in the peritoneal cavity (17/23, 74%). Recurrence rates were higher among node-positive patients (59% vs. 5%, P < 0.001). Nodal disease was more common in mAC (27%) and cAC (37%) than in GCA (11%); however, adenocarcinoma grade was not associated with nodal involvement. Nodal metastasis was more common in mAC and cAC compared with GCA and was the only significant predictor of recurrence in appendix cancer.

Nationwide incidence, treatment, and outcomes of patients 80 years and older with rectal adenocarcinomas: Analysis of 5,076 patients.

723 Background: Elderly patients have been underrepresented in randomized clinical trials of rectal cancer, and the value and tolerance of treatment options in this population remain unclear. We used the National Cancer Data Base (NCDB) to assess the incidence, treatment patterns, and overall survival (OS) outcomes of patients 80 years or older with newly diagnosed non-metastatic rectal adenocarcinomas. Methods: 5076 patients 80 years and older diagnosed with non-metastatic rectal adenocarcinomas from 2004 to 2013 were identified. Univariable and multivariable (MVA) analysis were performed to identify patient, tumor, and treatment characteristics associated with receipt of standard of care therapy (SOCT) and factors predictive of OS. SOCT was defined as surgical resection for Stage I patients and receipt of neoadjuvant therapy followed by surgical resection for Stage II/III patients. Kaplan-Meier curves were generated to assess the effect of stage and treatment received on overall survival. Results: At presentation, 935 (18.5%) were TXN0, 1557 (30.8%) were Stage I, 1552 (30.6%) were Stage II, and 1,032 (20.1%) were Stage III. The rates of patients receiving no therapy were: 29.6% for TXN0, 22.6% for Stage I, 16.5% for Stage II, and 12.2% for Stage III. The rates of patients not receiving SOCT were: 22.6% for Stage I, 51.4% for Stage II and 39.4% for Stage III cases. Survival was significantly worse for patients not receiving standard of care therapy: Stage I (52.1% receiving SOCT vs. 7.6% not receiving SOCT; p &lt; 0.01), Stage II (49.8% receiving SOCT vs. 14.5% not receiving SOCT; p &lt; 0.01), and Stage III (47.5% receiving SOCT vs. 10.2% not receiving SOCT; p &lt; 0.01). On MVA of patient, tumor, and treatment variables, receipt of SOCT was associated with improved OS for the entire cohort (p &lt; 0.01) and when examined by stage (p &lt; 0.01). Conclusions: In this nationwide sample of patient’s ≥ 80 years old with rectal cancer, there was a high rate of patients receiving no therapy. Those that did receive standard therapy achieved reasonable outcomes, suggesting avoidance of guideline care in this population should not be advised.

Neoadjuvant Chemotherapy for Nonmetastatic Esophago-Gastric Adenocarcinomas: A Systematic Review and Meta-Analysis

Objective: A systematic review and meta-analysis was performed to investigate the efficacy of neoadjuvant chemotherapy for nonmetastatic esophago-gastric adenocarcinomas. Methods: Electronic databases were searched systematically from January 1980 to July 2012 and a total of 2,587 patients from 17 randomized controlled trials were subjected to meta-analysis. The odds ratios (ORs) for overall survival (OS) and progression-free survival (PFS) were calculated. Results: Seventeen randomized controlled trials were obtained and various comparisons of treatment approaches were performed.Randomized controlled trials detected no differences in these comparisons:R0 resection for neoadjuvant chemotherapy versus none;Preoperative chemotherapy versus surgery alone: 3-year OS, 5-year OS, 5-year OS in Europe, 3-year PFS;Preoperative chemotherapy plus postoperative chemotherapy versus postoperative chemotherapy: 1-year OS, 5-year OS;Preoperative chemotherapy versus preoperative chemoradiotherapy: 3-year OS.Randomized controlled trials detected significant differences in these comparisons:Preoperative chemotherapy plus postoperative chemotherapy versus surgery alone: 3-year and 5-year PFS, 5-year OS;Subgroup analysis examining preoperative chemotherapy versus surgery alone: 5-year OS in Asia;Preoperative chemotherapy versus postoperative chemotherapy: 1-year OS.Conclusion: The current limited evidence suggests that preoperative chemotherapy can be applied to patients with nonmetastatic esophago-gastric adenocarcinomas (specifically, advanced esophago-gastric cancer). However, the results should be interpreted with caution because of the statistically low power and the heterogeneity among study designs; therefore, our results need validations in future studies.

Abstract 5003: The functional interplay between activated Stat5 and Stat3 in breast cancer formation and progression.

Abstract Cancer cells with stem cell-like characteristics are defined as cancer stem cells (CSCs) that are proposed to drive tumor initiation, progression and recurrence. Recent studies show the significance of epithelial-mesenchymal transition (EMT) in the induction of CSCs and their metastatic dissemination. Growth and colonization of the migrating stem cells require their re-differentiation and the reversal of EMT, mesenchymal to epithelial transition (MET), at the site of distant metastasis. We study the functional interplay between two related transcription factors, signal transducer and activator of transcription 5 (Stat5) and Stat3 in the genetic and epigenetic regulation of non-metastatic and metastatic breast cancer cells. Simultaneous activity of both Stats is observed in high percentage of human luminal breast cancers. In both normal and malignant cells, Stat5 activity is associated with cell proliferation, differentiation and survival, however, its activity in tumors is defined as a good prognostic marker due to response to antiestrogen therapy. During postlactational gland regression, called involution, P-Stat3 regulates lysosomal-mediated cell death, which is in contrast to its strong oncogenic function during mammary tumorigenesis. To gain insights into oncogenic functions of Stat5, we established a new mouse model which allows the investigation of genetic and epigenetic contributions in the initiation and progression of mammary tumors. In this model we used genetic manipulation of mammary stem cells (MaSCs) derived from primary tissue and the reconstitution of functional epithelium through transplantation into cleared fat pads to generate transgenic glands. The persistent activation of Stat5 during post-lactational involution resulted in the induction of non-metastatic adenocarcinomas, resembling human luminal-A breast cancer subtype. These tumors could be serially transplanted in BALB/c wild-type recipient mice and contain a small fraction of Lin-CD24lowCD44high tumor initiating cells. Both primary and secondary tumors show simultaneous activity of Stat5 and Stat3 and express estrogen and progesterone receptors (ER+PR+) and their downstream target genes like amphiregulin, RANKL and Wnt4. We performed microarray gene expression analysis of tumor tissues and P-Stat5 transgenic grafts and studied potential target genes, which can explain Stat5 oncogenic functions in tumor formation in contrast to its suppression effects on tumor cell migration. We are now studying the relative contribution of Stat5 and Stat3 in the regulation of metastatic process and transient EMT-MET changes. Our tumor model allows the identification of new genetic and epigenetic biomarkers, which are necessary for a better diagnosis and treatment of breast cancer and the prediction of invasive relapse. Citation Format: Vida Vafaizadeh, Bernd Groner. The functional interplay between activated Stat5 and Stat3 in breast cancer formation and progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5003. doi:10.1158/1538-7445.AM2013-5003

Stat5 assumes distinct functions in mammary gland development and mammary tumor formation

The mammary epithelium comprises luminal and basal cells which originate from multipotent mammary stem cells (MaSCs). They form ductal structures embedded in the mammary fat pad in virgin mice and differentiate during pregnancy into alveoli under the control of hormones and growth factors and the activation of specific transcription factors. Genetic manipulations of embryonic stem cells and the derivation of transgenic mice allowed the study of regulatory genes in mammary epithelial cells of particular differentiation states. We describe an alternative approach to investigate stage dependent gene functions in transgenic mammary glands based on ex vivo, genetically manipulated MaSCs and the reconstitution of functional epithelium upon their transplantation into cleared fat pads. Modification of MaSCs with Stat5 suppressing shRNA or a constitutively active variant of Stat5 showed that Stat5 assumes essential roles in alveolar lineage commitment, proliferation, differentiation and survival. Its persistent activation during post-lactational involution causes the formation of non-metastatic adenocarcinomas, resembling the human luminal breast cancer subtype. The tumor cells express estrogen and progesterone receptor (ER+PR+) and activated Stat3 and Stat5. They could become valuable to assess the therapeutic potential of anti-estrogens, aromatase inhibitors and Stat3 and Stat5 inhibition on tumor growth.

MUC16 Expression and Risk of Adenocarcinoma Metastases to Peritoneum, Pleura, Leptomeninges, and Brain

Approximately 5% to 15% of central nervous system metastases by solid tumors spread to the leptomeninges. Transmembrane MUC16 is thought to facilitate anchoring of metastases to other tissues particularly those expressing mesothelin such as pleura and peritoneum. Recently, we have demonstrated that mesothelin is also expressed in the leptomeninges. Mesothelin has a high affinity for MUC16 and mesothelin expressed by some adenocarcinomas. In this study, we evaluated MUC16 and mesothelin immunoreactivity by immunohistochemistry in 11 adenocarcinomas to the leptomeninges, 24 to mesothelin-negative brain, 8 metastases to mesothelin-expressing peritoneum/pleura, 22 to mesothelin-negative peripheral tissues, and 24 with no metastases. MUC16 was detected in 36% of leptomeningeal metastases and 10% of metastases to the brain. Adenocarcinoma metastases to mesothelin-expressing peritoneum or pleura exhibited extensive MUC16 in 75% of cases. In adenocarcinomas with local metastases to lymph nodes or no metastases, 53% or 38% had MUC16 immunoreactivity, respectively. Mesothelin-immunoreactivity was detected in 9% of metastases to the leptomeninges, 17% to the brain, none of the metastases to pleura/peritoneum, 50% of adenocarcinomas with local metastases to lymph nodes, etc, and 33% of adenocarcinomas without metastases. Mesothelin expression was significantly more common in nonmetastatic adenocarcinomas than in metastases to the pleura/peritoneum or leptomeninges. Our findings suggest that adenocarcinomas with MUC16 expression may have an increased risk for metastases to pleura/peritoneum but not the leptomeninges or brain.