11 research outputs found
Abstract 4833: Perfusion-based bioreactor culture of primary cancer tissue maintains tumor microenvironment complexity and allow <i>in-vitro</i> testing of immune blockade therapy
No full textAbstract
In vitro culture of primary cancer tissue is still very limited and the generation of patient derived xenograft determine the loss of human-cancer associated stroma. In this context, the use of 3D in vitro systems based on human tissue may be an innovative system to be exploited for keeping the tumor microenvironment (TME) complexity of the tissue in vitro.
Freshly excised colorectal (CRC) and breast cancer (BrCa) specimens were fragmented and cultured in 3D “sandwich-like format” between porous collagen scaffolds under perfusion flow (U-CUP, Cellec Biotek AG). The maintenance of tumor and immune-infiltrating cells, survival and phenotypic characterization were histologically assessed. In a second step cancer treatment were tested.
U-CUP culture allowed the preservation, viability and expansion of tumor tissue with concomitant stromal and immune cells. Expanding cancer cells were viable after 10 and 21 days (CRC and BrCa, respectively). Administration of anti-ER treatment to Lumina A ER+ BrCa was associated with decreased expansion of cancer tissue into the scaffold after 21 days. The maintenance of immune-infiltrating cells allowed testing of immune blockade therapy. Administration of anti-PDL1 antibody, alone or in combination with anti-CTLA4, to the culture medium was associated with increased expression of markers of immune-activation (i.e. IFNγ) and decreased expression of immunosuppressive cytokine IL10.
Preserving malignant, interstitial and immunocompetent cells comprised in surgically excised tumor specimens might allow a direct evaluation of the effects of various treatments on the complex TME. This engineered in vitro model could allow animal-free testing and it could be extended as a platform allowing the testing of innovative approaches for the treatment of human malignancies. Our findings shed the light on a promising system for selecting personalized treatment based on a patient’s tumor specific microenvironment.
Note: This abstract was not presented at the meeting.
Citation Format: Manuele Giuseppe Muraro, Simone Muenst, Celeste Manfredonia, Valentina Mele, Silvio Daester, Alexandar Tzankov, Luigi Terracciano, Walter Weber, Giulio C. Spagnoli, Giandomenica Iezzi, Ivan Martin, Savas D. Soysal. Perfusion-based bioreactor culture of primary cancer tissue maintains tumor microenvironment complexity and allow in-vitro testing of immune blockade therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4833. doi:10.1158/1538-7445.AM2017-4833</jats:p
Abstract 1582: Tumor-associated stromal cells increase malignancy of human colorectal cancers triggering EMT induction
No full textColorectal-vaginal fistula after rectal cancer resection: international comparative cohort study of characteristics and treatment
No full textA colorectal-vaginal fistula (CRVF) can occur as a complication of rectal cancer surgery. They can cause discomfort, repeated infection, need for treatment/further surgery, and a permanent stoma (an opening in the abdomen to collect bowel contents). This study looked at how often CRVF happened after surgery complicated by a leak where bowels ends have been joined together, how they were treated, and how likely patients were to live without a stoma 1 year after surgery. Researchers collected data on women from around the world who had rectal cancer surgery between 2014 and 2018 and developed a bowel leak (called anastomotic leakage). They compared those with and without a CRVF. A total of 88 out of 694 patients (12.7%) developed a CRVF. These patients more often had major surgery involving removal of nearby organs, including part of the vagina. They were more likely to have ongoing problems and needed more surgeries to manage them. Most had a temporary stoma, but only 29.5% could live without it after 1 year, compared with 48.7% of women without CRVF. CRVF is a serious complication that makes recovery harder. These patients are less likely to live without a stoma and usually need more surgery. However, if the leak is small, the chances of recovery without a permanent stoma are better
Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients
No full textStoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients
No full textBackground: The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2: 1). Results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding
Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort.
No full textObjective:To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL).Background:AL after RC resection often results in a permanent stoma.Methods:This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated.Results:This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76).Conclusions:The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies
Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort
No full textObjective:To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL).Background:AL after RC resection often results in a permanent stoma.Methods:This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated.Results:This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76).Conclusions:The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies
Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients
No full textBackground The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied.Methods Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1).Results Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days).Conclusion Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.The optimal treatment strategy for anastomotic leakage after restorative rectal cancer surgery remains unknown. This large, international collaborative study investigated various outcomes after four predefined treatment strategies for anastomotic leakage. Substantial differences were observed in patient and leakage characteristics, as well as outcomes following the four treatment strategies. However, no statistically significant differences were reported in stoma-free survival rates between active (vacuum) drainage and passive drainage
Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage
No full textObjective: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL). Background: AL after RC resection often results in a permanent stoma. Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated. Results: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76). Conclusions: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies
