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In patients operated on for low rectal cancer, 2-stage Turnbull-Cutait pull-through hand-sewn coloanal anastomosis provides benefits in terms of postoperative morbidity compared with standard hand-sewn coloanal anastomosis associated with diverting ileostomy and further ileostomy reversal.

To compare long-term results of these 2 techniques after ultralow rectal resection for rectal cancer.

In this randomized multicenter clinical trial, neither patients nor surgeons were blinded for technique. Patients were recruited in 3 centers. Patients undergoing ultralow anterior rectal resection needing hand-sewn coloanal anastomosis were randomly assigned to 2-stage Turnbull-Cutait pull-through hand-sewn coloanal anastomosis (n = 46) or standard hand-sewn coloanal anastomosis associated with diverting ileostomy (n = 46).

All patients underwent ultralow anterior resection. Patients assigned to the 2-stage Turnbull-Cutait pull-through group underwent exteriorization of a segment of left colon through the anal canal. After 6 to 10 days, the exteriorized colon was resected and a delayed hand-sewn coloanal anastomosis performed. For patients assigned to standard coloanal anastomosis, the hand-sewn coloanal anastomosis was performed with diverting ileostomy during the first operation. Ileostomy closure was scheduled after adjuvant treatment was completed in about 6 to 8 months.

The study aimed to compare the differences between the 2 groups in terms of long-term surgery-related morbidity, functional, and oncological outcomes at 3 years postoperatively. Data were analyzed from October 1, 2018, through October 31, 2021.

The 92 patients randomized in the first study were included for the 3-year follow-up. The overall morbidity rate in the 2 groups showed that 15 patients (16.3%) had complications with a difference of 6.52 (95% CI, −8.93 to 21.79). Nine patients (19.6%) and 6 patients (13.0%) in the 2-stage Turnbull-Cutait pull-through group and hand-sewn coloanal anastomosis group, respectively, had complications without statistically significant differences (P = .57). Oncological results were comparable between the groups. Long-term fecal continence in the CCA and TCA groups, respectively, assessed using the Wexner Incontinence Score was 10.9 (5.50-15.5) vs 13.0 (7.25-16.0; P = .92), Low Anterior Resection Syndrome score was 32.0 (21.0-37.0) vs 34.0 (23.2-38.5; P = .76), and Colorectal Functional Outcome score was 38.5 (23.0-47.1) vs 40.8 (23.3-58.2; P = .30).

In this study, after a 3-year follow-up period, 2-stage Turnbull-Cutait anastomosis for ultralow rectal cancer could be considered as a surgical alternative that has the valuable benefit of avoiding a temporary stoma with similar results in terms of morbidity, fecal continence, patient satisfaction, quality of life, and oncological outcomes when compared with hand-sewn coloanal anastomosis with ileostomy.

ClinicalTrials.gov Identifier: NCT01766661

Cholangiocarcinoma (CCA), a highly lethal tumor of the hepatobiliary system originating from bile duct epithelium, can be divided into the intrahepatic, hilar, and extrahepatic types. Due to its insidious onset and atypical early clinical symptoms, the overall prognosis is poor. One of the important factors contributing to the poor prognosis of CCA is the occurrence of perineural invasion (PNI), but the specific mechanisms regarding how it contributes to the occurrence of PNI are still unclear. The main purpose of this study is to explore the molecular mechanism leading to the occurrence of PNI and provide new ideas for clinical treatment.

CCA cell lines and Schwann cells (SCs) were stimulated to observe the changes in cell behavior. SCs cocultured with tumor supernatant and SCs cultured in normal medium were subjected to transcriptome sequencing to screen the significantly upregulated genes. Following this, the two types of tumor cells were cultured with SC supernatant, and the changes in behavior of the tumor cells were observed. Nonobese diabetic-severe combined immunodeficiency disease (NOD-SCID) mice were injected with cell suspension supplemented with nerve growth factor (NGF) via the sciatic nerve. Four weeks later, the mice were euthanized and the tumor sections were removed and stained.

Nerve invasion by tumor cells was common in CCA tissues. SCs were observed in tumor tissues, and the number of SCs in tumor tissues and the degree of PNI were much higher than were those in normal tissues or tissues without PNI. The overall survival time was shorter in patients with CCA with PNI than in patients without PNI. SCs were enriched in CCA tissues, indicating the presence of PNI and associated with poor prognosis in CCA patients. CCA was found to promote NGF secretion from SCs in vitro. After the addition of exogenous NGF in CCA cell culture medium, the proliferation activity and migration ability of CCA cells were significantly increased, suggesting that SCs can promote the proliferation and migration of CCA through the secretion of NGF. NGF, in turn, was observed to promote epithelial-mesenchymal transition in CCA through tropomyosin receptor kinase A (TrkA), thus promoting its progression. Tumor growth in mice shows that NGF can promote PNI in CCA.

In CCA, tumor cells can promote the secretion of NGF by SCs, which promotes the progression of CCA and PNI by binding to its high-affinity receptor TrkA, leading to poor prognosis.