Locally Advanced Adenocarcinoma of the Esophagus: Is Esophagectomy Associated with Improved Overall Survival?

BACKGROUND: Esophagectomy in locally advanced esophageal adenocarcinoma is challenging and carries risk. The value of esophagectomy in locally advanced esophageal adenocarcinoma is not well-defined. STUDY DESIGN: The National Cancer Database was used to identify patients with cT4 esophageal adenocarcinoma from 2004 to 2020. Multivariable regression was used to identify factors associated with use of esophagectomy. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing esophagectomy were 1:1 propensity score-matched to patients treated nonsurgically. Kaplan-Meier analysis was used to compare 5-year overall survival (OS). RESULTS: A total of 3,703 patients met inclusion criteria. Of those, 541 (15%) underwent esophagectomy, and 3,162 (85%) did not. Age 65 years or less (adjusted odds ratio [aOR] 1.69, 95% CI 1.33 to 2.14), White race (aOR 2.98, 95% CI 2.24 to 3.96), treatment in academic centers (aOR 1.64, 95% CI 1.33 to 2.02), private insurance (aOR 1.88, 95% CI 1.50 to 2.36), and tumors less than 6 cm (aOR 1.86, 95% CI 1.44 to 2.40) were associated with use of esophagectomy. Government of lack of insurance (hazard ratio [HR] 1.23, 95% CI 1.12 to 1.35), income <$46,000 (HR 1.11, 95% CI 1.03 to 1.20), treatment in nonacademic centers (HR 1.16, 95% CI 1.07 to 1.25), Charlson-Deyo Comorbidity Index 1 or more (HR 1.22, 95% CI 1.12 to 1.32), and tumors 6 cm or more (HR 1.20, 95% CI 1.09 to 1.32) were associated with risk of all-cause mortality. Esophagectomy (HR 0.50, 95% CI 0.44 to 0.56) and systemic therapy (HR 0.40, 95% CI 0.37 to 0.43) were associated with decreased risk of all-cause mortality. Patients undergoing esophagectomy had higher rates of 5-year OS (27.4% vs 13.2%, p < 0.0001) and longer median OS (24.71 vs 10.09 months, p < 0.0001). Among cT4b patients, those who underwent esophagectomy had higher rates of 5-year OS (24.5% vs 12.3%, p < 0.0001) and longer median OS (25.53 vs 11.01 months, p < 0.0001). CONCLUSIONS: In cT4 esophageal adenocarcinoma, esophagectomy is associated with improved rates of 5-year OS compared with nonsurgical treatment.

Locally advanced pancreatic cancer: Is surgical palliation associated with improved clinical outcome relative to medical palliation?

BACKGROUND: The value of palliative surgery in pancreatic cancer is not well-defined. METHODS: We queried the National Cancer Database for patients undergoing curative-intent resection, palliative surgery or medical palliation for clinical stage cT4N0-2M0 pancreatic cancer. Cohorts were 1:1:1 propensity-score-matched for comorbidities and stage. Kaplan-Meier method was used to compare overall survival for matched cohorts. RESULTS: 9,107 patients met inclusion criteria: 3,567 (39 â€‹%) underwent curative intent surgery, 1608 (18 â€‹%) surgical palliation, 3932 (43 â€‹%) medical palliation. Patients undergoing resection and surgical palliation had significant hospitalizations (11.0 â€‹± â€‹0.4 vs. 10.0 â€‹± â€‹0.3 days; p â€‹= â€‹0.821) and rates of readmission (8.1 â€‹% vs. 2.0 â€‹%; p â€‹< â€‹0.001). Patients undergoing surgical palliation demonstrated marginal increases in survival relative to those undergoing medical palliation (8.54 vs. 7.36 months; p â€‹< â€‹0.0001). CONCLUSION: In patients undergoing care for locally advanced pancreatic cancer, palliative surgery is associated with marginal improvement in survival but significant lengths of hospitalization and risk of readmission.

Clinical stage T2N0M0 rectal adenocarcinoma: Is radical resection associated with improved overall survival in patients with low-risk histology?

BACKGROUND: Prior studies evaluating the efficacy of local excision compared to radical resection in the treatment of rectal adenocarcinoma lacked sufficient power to identify differences in outcomes for patients with cT2 disease but low-risk histopathology. We compared the outcomes of local excision and radical resection for low-risk histopathology and high-risk histology of patients with cT2N0M0 rectal adenocarcinoma to assess their outcomes. METHODS: We queried the National Cancer Database for patients presenting with cT2N0M0 rectal adenocarcinoma between 2004 and 2019 and categorized them as low-risk histopathology or high-risk histology. We used the Cox proportional hazards model to identify factors associated with the risk of all-cause mortality. We 1:1 propensity-matched patients who underwent local excision to patients who underwent radical resection and used the Kaplan-Meier method to compare overall survival for matched cohorts. RESULTS: Of the 4,446 patients selected, we classified 1,206 (27%) as high-risk histology and 3,240 (73%) as low-risk histopathology. Among the patients with high-risk histology, 121 (10%) underwent local excision and 1,085 (90%) underwent radical resection. Among the patients with low-risk histopathology, 340 (10%) underwent local excision and 2,900 (90%) radical resections. Whereas radical resection was associated with decreased risk of all-cause mortality and increased overall survival for patients with high-risk histology, it was not for patients with low-risk histopathology. CONCLUSION: The overall survival of patients with low-risk histopathology with cT2N0M0 rectal adenocarcinoma who undergo local excision is similar to those of patients with low-risk histopathology who undergo radical resection, suggesting local excision is a reasonable approach for these patients. In contrast, radical resection provides a significant survival advantage for patients with high-risk histology and should remain their treatment of choice.

Rectal neuroendocrine tumors: Can they be observed?

BACKGROUND: Studies comparing approaches to managing rectal neuroendocrine tumors are underpowered by institutional series. The efficacy of expectant management relative to local excision and radical resection is poorly defined. METHODS: We queried the National Cancer Database to identify patients presenting with non-metastatic rectal neuroendocrine tumors between 2004 and 2019. Multivariable regression was used to identify factors associated with expectant management. Cox modeling was used to identify factors associated with all-cause mortality. Patients undergoing expectant management were 1:1:1 propensity score matched for demographics and comorbid disease to those undergoing radical resection and local excision. The Kaplan-Meier method was used to compare overall survival profiles for matched cohorts. RESULTS: A total of 6,316 patients met the inclusion criteria. Of these, 5,211 (83%) underwent local excision, 600 (9.5%) radical resection, and 505 (8%) expectant management. On multivariable regression, factors associated with expectant management included Black race, government insurance, and tumor size <2.0 centimeters. On Cox modeling, factors associated with mortality included age >65 years, male sex, government insurance, comorbidity score >0, tumor size >2 centimeters, and poorly differentiated histology. On comparison of matched cohorts: patients undergoing radical resection had longer hospitalizations and higher readmission rates than those undergoing local excision; there was no difference in overall survival between cohorts in patients with stage 1 disease; in stage 2 and 3 diseases, patients undergoing local excision and radical resection demonstrated improved rates of overall survival relative to those undergoing expectant management. CONCLUSION: Expectant management is a reasonable approach for patients with stage 1 rectal neuroendocrine tumors. Local excision should be the preferred treatment option for those presenting with stage 2/3 disease.

Effects of hypertonic (NaCl) two-dimensional and three-dimensional culture conditions on the properties of cartilage tissue engineered from an expanded mature bovine chondrocyte source.

Clinically relevant mature cartilage cells (chondrocytes) present challenges for use in cartilage tissue engineering applications, given their low capacity for cell division and tissue production. Since the in situ environment of chondrocytes is hypertonic relative to standard culture medium conditions, in this study we tested the hypothesis that using culture medium of a hypertonic, more physiologic osmolarity during both two-dimensional (2D) expansion of mature bovine chondrocytes (MBCs) and their subsequent encapsulation culture in three-dimensional (3D) agarose hydrogel constructs produces improved engineered tissue construct mechanical and biochemical properties. Results demonstrate that 2D expansion of MBCs in hypertonic (NaCl) medium before encapsulation yielded improved construct mechanical properties. However, 3D encapsulation culture of cells in hypertonic (NaCl) medium yielded poorer construct mechanical properties. Osmolarity-related differences in construct biochemical content and organization may have contributed to differences in mechanical properties, as construct glycosaminoglycan content correlated moderately with construct mechanical properties, and construct collagen distribution varied between 3D osmotic culture groups. Results of this study suggest that application of hypertonic (NaCl) medium during 2D mature chondrocyte expansion, but not 3D encapsulated chondrocyte culture, may serve as a convenient and inexpensive method for improving mechanical properties of expanded cell-seeded constructs.