Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy alone for patients with locally advanced rectal cancer: a propensity-score-matched analysis combined with SEER validation.

BACKGROUND: Neoadjuvant therapy followed by radical surgery is recommended for locally advanced rectal cancer (LARC). But radiotherapy can cause potential adverse effects. The therapeutic outcomes, postoperative survival and relapse rates between neoadjuvant chemotherapy (N-CT) and neoadjuvant chemoradiotherapy (N-CRT) patients have rarely been studied. METHODS: From February 2012 to April 2015, patients with LARC who underwent N-CT or N-CRT followed by radical surgery at our center were included. Pathologic response, surgical outcomes, postoperative complications and survival outcomes (including overall survival [OS], disease-free survival [DFS], cancer-specific survival [CSS] and locoregional recurrence-free survival [LRFS]) were analyzed and compared. Concurrently, the Surveillance, Epidemiology, and End Results Program (SEER) database was used to compare OS in an external source. RESULTS: A total of 256 patients were input into the propensity score-matching (PSM) analysis, and 104 pairs remained after PSM. After PSM, the baseline data were well matched and there was a significantly lower tumor regression grade (TRG) (P < 0.001), more postoperative complications (P = 0.009) (especially anastomotic fistula, P = 0.003) and a longer median hospital stay (P = 0.049) in the N-CRT group than in the N-CT group. No significant difference was observed in OS (P = 0.737), DFS (P = 0.580), CSS (P = 0.920) or LRFS (P = 0.086) between the N-CRT group and the N-CT group. In the SEER database, patients who received N-CT had similar OS in both TNM II (P = 0.315) and TNM III stages (P = 0.090) as those who received N-CRT. CONCLUSION: N-CT conferred similar survival benefits but caused fewer complications than N-CRT. Thus, it could be an alternative treatment of LARC.

Development and external validation of prognostic nomograms for liver disease-free and overall survival in locally advanced rectal cancer with neoadjuvant therapy: a post cohort study based on the FOWARC trial.

Background: There is still a lack of nomograms that can accurately predict liver metastasis and poor prognosis after neoadjuvant therapy for locally advanced rectal cancer (LARC). Effective nomograms may help clinicians better identify LARC patients with potential high-risk risks, so as to carry out more targeted monitoring, treatment and follow-up. Methods: The nomograms were based on the FOWARC trial (NCT01211210), which included 302 LARC patients who underwent neoadjuvant treatment before surgery at the Sixth Affiliated Hospital of Sun Yat-sen University from 2011 to 2014. The predictive accuracy and discriminative ability of the nomograms were determined by the concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling and a prospective study on 100 patients in 2017. Results: The 3-year liver disease-free survival (LDFS) rate after neoadjuvant treatment for LARC was 91.65% (training cohort 92.22%, validation cohort 90.01%). Factors associated with LDFS were hepatitis B virus (HBV) infection, anemia, lymph node number, postoperative T stage and tumor nodule, which were all included in the nomogram for LDFS. The C-indies of the nomogram for LDFS were 0.828 and 0.845 in the training and validation cohorts. The 3-year overall survival (OS) rate was 94.14% (training cohort 94.13%, validation cohort 94.05%). Factors in the nomogram for OS were mesorectal fascia involvement (MRF), postoperative N stage, pathological differentiation, tumor nodule and neural invasion. The C-indies of the nomogram for predicting OS were 0.73 and 0.774 in the training and validation cohorts. The calibration curve for the survival probability showed good agreement between the nomogram predictions and the actual observations. Conclusions: The nomograms established in this study can effectively predict LDFS and has good clinical application potential for OS in LARC patients treated with neoadjuvant therapy.

Apoptosis pattern and alterations of expression of apoptosis-related factors of supporting cells in Kölliker's organ in vivo in early stage after birth in rats.

Kölliker's organ is a temporary but indispensable structure in the development of the cochlea. Supporting cells (SCs) within it release adenosine 5'-triphosphate (ATP), which may play a crucial role in cochlear development before the onset of hearing. To reveal the apoptosis of Kölliker's organ in new-born rats, we studied the morphological changes and expression of apoptosis-related factors during early postnatal development. We found SCs in Kölliker's organ decreased in number and changed in appearance along the cochlea apex-to-base gradient, and the expression of caspase-3, caspase-8, caspase-9 and bcl-2 in Kölliker's organ of the cochlea fluctuated along the course of postnatal development, with an expression peak at postnatal day 3. This study demonstrates a time-dependent degeneration of Kölliker's organ during postnatal cochlea development, which might be triggered by endogenous factors.