Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation

Objective Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. Methods The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC. Results A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence. Conclusion Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer.

Dysfunction of Apoptosis and Autophagy Correlates with Local Recurrence in Esophageal Squamous Cell Carcinoma After Definitive Chemoradiation

Objective: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. Methods: The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC.Results: A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence.Conclussion: Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer.

Clinical Statistical Analysis with Comparison between Pelvic and Non-pelvic Chondrosarcoma

Objectives: Chondrosarcomas are rare tumors with a variable biological characteristic. Their treatment clinically and surgically is controversial. Analysis of the clinical statistics and prognostic factors of pelvic chondrosarcoma provides a reference for clinical diagnosis and treatment. Methods: A total of 73 cases of chondrosarcoma were collected, including 24 pelvic samples, from 2008 to 2017 from the hospital database and divided into two groups: pelvic chondrosarcoma and non-pelvic chondrosarcoma. The clinical characteristics and prognostic factors of pelvic chondrosarcoma were analyzed using different statistical methods. Results: Among the 24 pelvic chondrosarcoma patients, the ratio of male to female was 1.4:1, and the median age was 43.5 years. According to the classification proposed by Enneking, there were five grade I, 14 grade II, and five grade III. Histological grading of chondrosarcoma was grade I in one case, II in 15 cases, and III in eight cases. The histological type was 17 conventional, three dedifferentiated, two secondary, one myxoid, and one mesenchymal. The overall survival rates for 24 cases at three, five, and 10 years were 82.2±8.1%, 77.3±8.9%, and 52.4±12.1%, respectively. The local recurrence rate of pelvic chondrosarcoma after surgical resection (83.3%) was significantly higher than that of other sites (34.7%), and the difference was statistically significant (p < 0.001). The final proportion of amputation rate (50.0%) was also higher than other parts (20.4%), with a statistically significant difference (p =0.010). The total survival of the two groups was not significantly different (p =0.216). Conclusions: Chondrosarcoma of bone generally has an excellent prognosis when optimally diagnosed and treated by an experienced team of specialists. Pelvic chondrosarcoma has a higher local recurrence rate than the other sites and tends to result in amputation. Early local recurrence after surgery indicates a poor prognosis.

Mesonephric-Like Adenocarcinoma of the Endometrium: Diagnostic Advances to Spot This Wolf in Sheep’s Clothing. A Review of the Literature

Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very challenging to diagnose. In mesonephric adenocarcinoma a variety of growth patterns can be present within the same tumor, as a result of which they can be misinterpreted and diagnosed as low-grade endometrioid adenocarcinoma, clear cell carcinoma, or even serous carcinoma and carcinosarcoma. We report a case of mesonephric-like adenocarcinoma misdiagnosed as a low-grade endometrioid endometrial adenocarcinoma that had an early local recurrence and metastasized to the liver and the lungs. Histopathological, immunohistochemical and molecular analysis were performed and compared to published literature, providing a comprehensive overview of the current knowledge. Databases (Pubmed, Web of Science, Google Scholar) were searched with a combination of the following search terms: mesonephric-like, mesonephric, adenocarcinoma, carcinoma, uterine body, uterine corpus, endometrium. Mesonephric-like adenocarcinoma is a difficult-to-diagnose entity. Advanced diagnostics, including improved morphologic, immunohistochemical and molecular knowledge can help develop new therapeutic strategies against this specific subtype of endometrial cancer with an aggressive clinical behavior.

Unexplained neoplastic anastomotic recurrence after right hemicolectomy: a case report

Background Anastomotic recurrences of the colon are postulated to arise due to inadequate margins, tumor implantation by exfoliated cells, altered biological properties of bowel anastomosis, and missed synchronous lesions. In this paper, a case of unexpected early local recurrence after surgery for colon cancer is presented. Case presentation A 68-year-old Caucasian man underwent right hemicolectomy for invasive G2 adenocarcinoma. Two months later, endoscopy revealed a wide and well-functioning anastomosis with a hyperemic, hard, and thickened mucosal area of about 2 cm in diameter. Biopsies showed the presence of an adenocarcinoma with the same grading of the previous lesion. Ten days later, the patient underwent a new intervention; the last 10 cm of the ileum and half of the remaining transverse colon were resected, and the patient started adjuvant therapy. Specimen examination confirmed the presence of an adenocarcinoma (G2) penetrating the muscular layer of the wall; also, in this case, resection edges were free from tumoral invasion, and the removed lymph nodes were exempt from neoplastic colonization. The patient was seen in follow-up for about 5 years, and he did not show local or systemic manifestations. Conclusions Whenever a neoplastic recurrence on the anastomotic line occurs, in the presence of negative intestinal margins, as usual in right colectomies, the implantation of neoplastic cells could be the possible cause.

The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy

Background The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n = 34) and did not (n = 81) experience a recurrence within 6 months postoperatively. Results Multivariate analyses demonstrated postoperative CA19–9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P < 0.001, P = 0.001, and P = 0.010, respectively). A subgroup analysis showed patients with (n = 51) and without (n = 64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19–9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence. Conclusions CA19–9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.

The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy

Background The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy. Methods One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n=34) and did not (n=81) experience a recurrence within 6 months postoperatively. Results Multivariate analyses demonstrated postoperative CA19-9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P<0.001, P=0.001, and P=0.010, respectively). A subgroup analysis showed patients with (n=51) and without (n=64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19-9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence. Conclusions CA19-9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.