This is the Scientific Surgery Archive, which contains all randomized clinical trials in surgery that have been identified by searching the top 50 English language medical journal issues since January 1998. Compiled by Jonothan J. Earnshaw, former Editor-in-Chief, BJS

Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy. BJS 2019; 106: 1404-1414.

Published: 14th June 2019

Authors: I. Ubink, A. C. F. Bolhaqueiro, S. G. Elias, D. A. E. Raats, A. Constantinides, N. A. Peters et al.

Background

Patients with peritoneal metastases from colorectal cancer have a poor prognosis. If the intraperitoneal tumour load is limited, patients may be eligible for cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). This treatment has improved overall survival, but recurrence rates are high. The aim of this study was to create a preclinical platform for the development of more effective intraperitoneal chemotherapy strategies.

Method

Using organoid technology, five tumour cultures were generated from malignant ascites and resected peritoneal metastases. These were used in an in vitro HIPEC model to assess sensitivity to mitomycin C (MMC) and oxaliplatin, the drugs used most commonly in HIPEC. The model was also used to test a rational combination treatment involving MMC and inhibitors of the checkpoint kinase ATR.

Results

MMC was more effective in eliminating peritoneal metastasis‐derived organoids than oxaliplatin at clinically relevant concentrations. However, the drug concentrations required to eliminate 50 per cent of the tumour cells (IC50) were higher than the median clinical dose in two of five organoid lines for MMC, and all five lines for oxaliplatin, indicating a general resistance to monotherapy. ATR inhibition increased the sensitivity of all peritoneal metastasis‐derived organoids to MMC, as the IC50 decreased 2·6–12·4‐fold to well below concentrations commonly attained in clinical practice. Live‐cell imaging and flow cytometric analysis showed that ATR inhibition did not release cells from MMC‐induced cell cycle arrest, but caused increased replication stress and accelerated cell death.

Conclusion

Peritoneal metastasis‐derived organoids can be used to evaluate existing HIPEC regimens on an individual‐patient level and for development of more effective treatment strategies.

Surgical relevance

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has improved prognosis of patients with peritoneal metastases from colorectal cancer, but disease recurrence is common. More effective and personalized HIPEC is urgently needed. Organoid technology is frequently used for drug screens, as patient‐derived organoids can accurately predict clinical therapeutic response in vitro.

Full text

You may also be interested in

Original article

Early MRI predictors of disease‐free survival in locally advanced rectal cancer from the GRECCAR 4 trial. BJS 2019; 106: 1530-1541.

Authors: S. Nougaret, F. Castan, H. Forges, H. A. Vargas, B. Gallix, S. Gourgou et al.

Original article

Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

Authors: B. Garlipp, P. Gibbs, G. A. Van Hazel, R. Jeyarajah, R. C. G. Martin, C. J. Bruns et al.

Original article

Population‐based study of the impact of small bowel obstruction due to adhesions on short‐ and medium‐term mortality.

Authors: R. Behman, A. B. Nathens, B. Haas, N. Look Hong, P. Pechlivanoglou, P. Karanicolas et al.

Original article

Prospective cohort study of appendicectomy for treatment of therapy‐refractory ulcerative colitis.

Authors: M. E. Stellingwerf, S. Sahami, D. C. Winter, S. T. Martin, G. R. D'Haens, G. Cullen et al.

Original article

Long‐term follow‐up of the AVOD randomized trial of antibiotic avoidance in uncomplicated diverticulitis. BJS 2019; 106: 1542-1548.

Authors: D. Isacson, K. Smedh, M. Nikberg, A. Chabok

Original article

Pushing the boundaries of pelvic exenteration by maintaining survival at the cost of morbidity. BJS 2019; 106: 1393-1403.

Authors: R. L. Venchiarutti, M. J. Solomon, C. E. Koh, J. M. Young, D. Steffens

Systematic review

Meta‐analysis of the role of colonoscopy after an episode of left‐sided acute diverticulitis. BJS 2019; 106: 988-997.

Authors: S. J. Rottier, S. T. Dijk, A. A. W. Geloven, W. H. Schreurs, W. A. Draaisma, W. A. Enst et al.

Randomized clinical trial

Multicentre randomized clinical trial of colonic J pouch or straight stapled colorectal reconstruction after low anterior resection for rectal cancer.

Authors: S. Pucciarelli, P. Del Bianco, U. Pace, F. Bianco, A. Restivo, I. Maretto et al.

Review

Mechanisms of immunogenicity in colorectal cancer. BJS 2019; 106: 1283-1297.

Authors: T. O. Sillo, A. D. Beggs, D. G. Morton, G. Middleton

Systematic review

Meta‐analysis of the effect of extending the interval after long‐course chemoradiotherapy before surgery in locally advanced rectal cancer. BJS 2019; 106: 1298-1310.

Authors: É. J. Ryan, D. P. O'Sullivan, M. E. Kelly, A. Z. Syed, P. C. Neary, P. R. O'Connell et al.

Randomized clinical trial

Randomized clinical trial of accelerated enhanced recovery after minimally invasive colorectal cancer surgery (RecoverMI trial). BJS 2019; 106: 1311-1318.

Authors: B. K. Bednarski, T. P. Nickerson, Y. N. You, C. A. Messick, B. Speer, V. Gottumukkala et al.

Original article

Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy.

Authors: J. Erlandsson, D. Pettersson, B. Glimelius, T. Holm, A. Martling