Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.

BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.

Fosaprepitant for postoperative nausea and vomiting in patients undergoing laparoscopic gastrointestinal surgery: a randomised trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear. METHODS: In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours. RESULTS: The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group. CONCLUSIONS: Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension. CLINICAL TRIAL REGISTRATION: NCT04853147.

Factors associated with prolonged postoperative length of hospital stay after laparoscopic colorectal cancer resection: a secondary analysis of a randomized controlled trial.

BACKGROUND: The postoperative length of hospital stay (PLOS) is an important indicator of surgical quality. We identified perioperative factors that affect prolonged PLOS (PPLOS) after laparoscopic colorectal cancer resection, which is the preferred surgical approach for colorectal cancer, the third most common cancer. METHODS: This study was a secondary analysis of a randomized trial (clinicaltrials.gov ID: NCT03160144) that included 280 patients who underwent laparoscopic colorectal cancer resection. The primary outcome was a PPLOS, defined as a PLOS that was longer than the median PLOS. Baseline, anesthetic, surgical, and postoperative management factors were included in the univariate and multivariate analyses to identify factors influencing PPLOS. RESULTS: The median PLOS was 10 days, and 117 patients had a PPLOS. We identified six influencing factors for PPLOS: preoperative pulse oxygen saturation < 96% (odds ratio [OR], 3.09 [95% confidence interval (CI) 1.38-6.92]; P = 0.006), distant tumor metastasis (OR, 0.34 [95% CI 0.13-0.91]; P = 0.031), the Miles procedure or left hemicolectomy (OR, 4.51 [95% CI 1.67-12.18]; P = 0.003), perioperative surgical events (OR, 2.44 [95% CI 1.25-4.76]; P = 0.009), postoperative albumin infusion (OR, 2.19 [95% CI 1.14-4.19]; P = 0.018), and postoperative early ambulation (OR, 0.35 [95% CI 0.18-0.68]; P = 0.002). Further stratified analysis showed that postoperative albumin infusion might be a risk factor for PPLOS, even in patients with a preoperative albumin level < 40 g/L (OR, 2.29 [95% CI 0.98-5.34]; P = 0.056) or duration of surgery ≥ 3 h (OR, 2.52 [95% CI 1.08-5.87]; P = 0.032). CONCLUSIONS: A low preoperative pulse oximetry reading, complex surgical procedures, perioperative surgical events, and postoperative albumin infusion may be risk factors for PPLOS after laparoscopic colorectal cancer resection, whereas distant tumor metastasis and postoperative early ambulation might be protective factors. The association between postoperative albumin infusion, a modifiable factor, and PLOS or clinical outcomes warrants further investigation.

Postoperative Nausea and Vomiting in Female Patients Undergoing Laparoscopic Gastrointestinal Surgery with Double Prophylactic Therapy.

Purpose Postoperative nausea and vomiting (PONV) is a major problem after surgery. This study aimed to demonstrate the incidence of PONV and the potential associated factors in female patients undergoing laparoscopic gastrointestinal surgery against the background of double prophylactic therapy. Methods Our retrospective study recruited 109 female patients undergoing laparoscopic gastrointestinal surgery with double prophylactic therapy, combining palonosetron with dexamethasone, from October 2020 to March 2021, at the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Patient characteristics and perioperative management factors were included in univariate and multivariate analyses to identify factors influencing PONV. Results Four patients lacked complete records, and of the 105 patients included in the final analysis, 53 (50.5%) patients developed PONV. Two influencing factors for PONV were identified: a history of chemotherapy (odds ratio [OR] 0.325, 95% confidence interval [CI] 0.123-0.856; p = 0.023) and dosage of hydromorphone ≥ 0.02 mg/kg (OR 2.857, 95% CI 1.247-6.550; p = 0.013). The performance of the multivariate logistic regression was evaluated by analyzing receiver operating characteristic curves, resulting in an area under the curve value of 0.673. Conclusion The incidence of PONV remains high in female patients undergoing laparoscopic gastrointestinal surgery, even with double prophylactic therapy. A dosage of hydromorphone ≥ 0.02 mg/kg may increase risk of PONV, whereas a history of chemotherapy might be a protective factor.

Observer's Assessment of Alertness/Sedation-based titration reduces propofol consumption and incidence of hypotension during general anesthesia induction: A randomized controlled trial.

Administration of a single propofol bolus dose for anesthesia induction causes hypotension. We included 160 patients (74 males and 86 females; mean age, 42.4 ± 10.7 [range: 18-60] years) with the American Society of Anesthesiologists status I-II undergoing elective surgery under general anesthesia. Using simple randomization, the patients were divided into a conventional group (n = 80; received 2 mg/kg propofol at a rate of 250 mg/min) and titrated group (n = 80; received propofol at a rate of 1 mg/kg/min until the Observer's Assessment of Alertness/Sedation scale score reached 1 point). Fentanyl (4 µg/kg) and cisatracurium (0.2 mg/kg) were administered, as appropriate. Systolic blood pressure, diastolic blood pressure, mean blood pressure, and heart rate were recorded at different time points. Propofol consumption, hypotension, and other adverse events were recorded. All the patients were intubated without awareness. Compared with the conventional group, the titrated group showed more stable blood pressure (p < 0.05), as well as a lower decrease in systolic blood pressure, mean blood pressure at 1 and 3 min, and diastolic blood pressure at 1 min after propofol administration (p < 0.01). Moreover, compared with the conventional group, the titrated group showed a lower post-intubation hypotension incidence (9 vs. 19 cases; p = 0.04), as well as lower total propofol dosage and propofol dose per kilogram of body weight (93.57 ± 14.40 mg vs. 116.80 ± 22.37 mg and 1.73 ± 0.27 mg/kg vs. 2.02 ± 0.08 mg/kg, respectively, p < 0.01). Compared with conventional propofol usage, titrated propofol administration can reduce the incidence of hypotension and propofol consumption during anesthesia induction.

Role of Nox2 and p22phox in Persistent Postoperative Hypertension in Aldosterone-Producing Adenoma Patients after Adrenalectomy.

Adrenal aldosterone-producing adenoma (APA), producing the salt-retaining hormone aldosterone, commonly causes secondary hypertension, which often persists after unilateral adrenalectomy. Although persistent hypertension was correlated with residual hormone aldosterone, the in vivo mechanism remains unclear. NADPH oxidase is the critical cause of aldosterone synthesis in vitro. Nox2 and p22phox comprise the NADPH oxidase catalytic core, serving to initiate a reactive oxygen species (ROS) cascade that may participate in the pathology. mRNAs of seven NADPH oxidase isoforms in APA were evaluated by RT-PCR and Q-PCR and their proteins by immunohistochemistry and Western blotting. NADPH oxidase activity was also detected. Nox2 and p22phox were especially abundant in APA. Particularly higher Nox2 and p22phox gene and protein levels were seen in APA than controls. Significant correlations between Nox2 mRNA and aldosterone synthase (CYP11B2) mRNA (R = 0.66, P < 0.01) and Nox2 protein and baseline plasma aldosterone concentration (PAC) (R = 0.503, P < 0.01) were detected in APA; however, none were found between p22phox mRNA, CYP11B2 mRNA, p22phox protein, and baseline PAC. Importantly, we found that Nox2 localized specifically in hyperplastic zona glomerulosa cells. In conclusion, our results highlight that Nox2 and p22phox may be directly involved in pathological aldosterone production and zona glomerulosa cell proliferation after APA resection.