Perineural invasion in cervical cancer: A multicenter retrospective study.

OBJECTIVE: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. METHODS: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. RESULTS: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. CONCLUSION: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

Prediction study of prognostic nutrition index on the quality of life of patients with cervical cancer undergoing radiotherapy and chemotherapy.

Objective: To assess the prognostic nutritional index (PNI) and quality of life (QOL) of patients with cervical cancer (CC) who underwent radiotherapy and chemotherapy and to reveal the effect of PNI on QOL and its prognostic value. Methods: A total of 138 CC patients who underwent radiotherapy and chemotherapy in the Second Affiliated Hospital of Fujian Medical University from January 2020 to October 2022 were selected as the study subjects via convenient sampling. According to the PNI cut-off value of 48.8, they were divided into a high-PNI group and a low-PNI group, and the quality of life of the two groups was compared. The Kaplan-Meier method was used to draw the survival curve, and the Log-Rank test was employed to compare the survival rates of the two groups. Results: The scores of physical functioning and overall QOL in the high-PNI group were significantly higher than those in the low-PNI group (P < 0.05). The scores of fatigue, nausea and vomiting, pain and diarrhea were higher than those in the low-PNI group, and the difference was statistically significant (P < 0.05). The objective response rates were 96.77% and 81.25% in the high-PNI group and the low-PNI group, respectively, and the difference was statistically significant (P = 0.045). The 1-year survival rates of patients with high PNI and low PNI were 92.55% and 72.56% in the high-PNI group and the low-PNI group, respectively; the difference in survival rates was statistically significant (P = 0.006). Conclusion: The overall quality of life of CC patients with low PNI receiving radiotherapy and chemotherapy is lower than that of patients with high PNI. Low PNI reduces the tolerance to radiotherapy and chemotherapy and the objective response rate, which can be used as a prognostic indicator for cervical cancer patients.

Pregnancy-induced changes to the gut microbiota drive macrophage pyroptosis and exacerbate septic inflammation.

The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.

The long-term outcomes of clinical responders to neoadjuvant chemotherapy followed by radical surgery in locally advanced cervical cancer.

OBJECTIVE: To compare the long-term oncological outcome of neoadjuvant chemotherapy before radical surgery (NCRS) and definitive chemoradiotherapy (DR) for stage IB2 and IIA2 cervical squamous cell carcinoma. METHODS: The clinical outcome of 480 patients with stage IB2 and IIA2 cervical cancer (308 clinical responders, 111 clinical non-responders, 61 unclear) who underwent NCRS (and subgroup assessments) were compared with those of 233 patients who underwent DR. RESULTS: The clinical response rate was 73.5% in the NCRS group. Multivariate COX regression analyses revealed that NCRS was not correlated with the 5-year overall survival (OS) rate (p = 0.067) or disease-free survival (DFS) rate (p = 0.249). In a subgroup of NCRS, the clinical response group was also shown to be a protective independent factor of 5 year OS rate compared to the DR group (aHR, 0.403; 95% CI, 0.209-0.777), but had no correlation with the 5 year DFS rate (p = 0.089). On the other hand, the clinical non-response group had no correlation with the 5 year OS rate (p = 0.780) or DFS rate (p = 0.669). CONCLUSION: Clinical responders who underwent NCRS exhibited a better oncological outcome compared to those who underwent DR. International Clinical Trials Registry Platform Search Port, http://apps.who.int/trialsearch/ ; CHiCTR1800017778.

Cervical cancer invading the uterine corpus and sigmoid colon: A case report.

Early-stage cervical cancer rarely extends to the uterine corpus and invades the serosal layer. Here, we present a case of cervical cancer extending to the uterine corpus and then penetrating the myometrium to invade the sigmoid colon. Transabdominal type C2 radical hysterectomy, bilateral salpingo-oopherectomy, pelvic lymphadenectomy, and sigmoid resection were performed. The patient then underwent chemotherapy as she was unable to tolerate chemoradiotherapy. She recovered well and was followed up for 14 months. Our report reveals that the uterine corpus can be a route of tumor metastasis in cervical cancer.

Effect of modified no-touch laparoscopic radical hysterectomy on outcomes of early stage cervical cancer: A retrospective cohort study.

OBJECTIVES: We aimed to compare the prognosis of modified no-touch laparoscopic radical hysterectomy (MLRH) and laparoscopic radical hysterectomy (LRH) on survival in patients with early stage cervical cancer. MATERIALS AND METHODS: The clinicopathological data of patients with stage IB1 and IIA1 cervical cancer, who underwent radical surgery between 2014 and 2019, were retrospectively reviewed. The 5-year disease-free survival (DFS) and overall survival (OS) were compared between the MLRH and LRH groups using the Kaplan-Meier method. Independent prognostic factors for 5-year DFS and OS were identified using multivariate, forward, stepwise Cox proportional hazards regression models. RESULTS: A total of 223 patients with stage IB1 and IIA1 cervical cancer were included. Kaplan-Meier analysis revealed that the 5-year DFS and OS rates in the MLRH (n = 81) group were significantly higher than those in the LRH group (n = 142) (DFS, 94.5% vs. 78.8%, p = 0.007; OS, 96.7% vs. 87.6%, p = 0.033). No significant differences were identified between the two groups in terms of operative time, blood loss, transfusion requirement, and intraoperative or postoperative complications. MLRH was an independent prognostic factor associated with increased 5-year DFS (adjusted hazard ratio [HR], 0.202; 95% confidence interval [CI], 0.069-0.594; p = 0.004) and 5-year OS (adjusted HR, 0.163; 95% CI, 0.035-0.748; p = 0.020). CONCLUSION: The oncologic outcomes were superior with MLRH than with LRH in patients with stage IB1 and IIA1 cervical cancer. Contact of cervical tumor cells with the pelvic cavity likely explains the worse prognosis associated with LRH.

Combination of Estrogen Receptor Alpha and Histological Type Helps to Predict Lymph Node Metastasis in Patients with Stage IA2 to IIA2 Cervical Cancer.

OBJECTIVE: This study aimed to identify a subset of patients with stage IA2 to IIA2 cervical cancer who are at low risk of lymph node metastasis (LNM) using pathological parameters including estrogen receptor alpha (ERα) and progesterone receptor (PR). METHODS: The clinical data of patients with stage IA2 to IIA2 cervical cancer who underwent radical surgery between 2014 and 2015 were retrospectively reviewed. Immunohistochemical staining was used to determine the expression of ERα and PR. A low-risk criterion for LNM was identified using logistic regression analysis, and its performance was estimated through receiver-operating characteristic curve analysis. RESULTS: Of 263 patients, 57 (21.7%) had pathological LNM. ERα (adjusted odds ratio [aOR], 7.582; 95% confidence interval [CI], 2.991-19.222; P < 0.001) and squamous cell carcinoma (aOR, 3.520; 95% CI, 1.887-6.568; P < 0.001) were identified as independent predictors for no LNM by multivariate logistic regression analysis, while PR had no effect on LNM. The rate of LNM was 1.4% for low-risk patients (n = 73) identified as ERα positive with squamous cell carcinoma. The 5-year disease-free survival in low-risk patients was significantly greater than in those negative for ERα and/or those with non-squamous cell carcinoma (96.9% vs 80.1%, P = 0.002). CONCLUSION: ERα positivity and squamous cell carcinoma are associated with a low risk of LNM in patients with stage IA2 to IIA2 cervical cancer. Hence, those patients without a low risk of LNM could be considered for definitive chemoradiotherapy to avoid unnecessary surgery.

Preoperative magnetic resonance imaging criteria for predicting lymph node metastasis in patients with stage IB1-IIA2 cervical cancer.

OBJECTIVE: This study aimed to identify patients with stage IB1-IIA2 cervical cancer at low risk for lymph node metastasis (LNM) using preoperative magnetic resonance imaging (MRI) parameters. METHODS: Clinical and MRI data of patients with stage IB1-IIA2 cervical cancer who underwent radical surgery between 2010 and 2015 were retrospectively reviewed. Clinical stage IB1-IIA2 cervical cancer was diagnosed according to the 2009 International Federation of Gynecology and Obstetrics staging system. The low-risk criteria for LNM were identified using logistic regression analysis. The performance of the logistic regression analysis was estimated through receiver operating characteristic curve analysis. RESULTS: Of 453 patients, 105 (23.2%) exhibited pathological LNM (p-LNM). The maximal tumor diameter (adjusted odds ratio [aOR], 1.586; 95% confidence interval [CI], 1.312-1.916; p < 0.001) and LNM (aOR, 2.384; 95% CI, 1.418-4.007; p = 0.001) on preoperative MRI (m-LNM) were identified as independent risk factors for p-LNM using a multivariate logistic analysis. The p-LNM rate was 4.0% for low-risk patients (n = 124) identified using the current criteria (maximal tumor diameter <3.0 cm and no sign of m-LNM). The 5-year disease-free survival rate of low-risk patients was significantly greater than the rate of patients with a maximal tumor diameter ˃3.0 cm and/or signs of m-LNM (90.4% vs. 82.1%; p = 0.033). CONCLUSIONS: The low-risk criteria for p-LNM were a maximal tumor diameter <3.0 cm and no sign of m-LNM. Patients with stage IB1-IIA2 cervical cancer at low risk for m-LNM could be candidates for radical surgery; hence, they have a lesser need for adjuvant chemoradiotherapy, thus avoiding the severe comorbidities it causes.

Gut microbiota accelerates cisplatin-induced acute liver injury associated with robust inflammation and oxidative stress in mice.

BACKGROUND: Gut microbiota has been reported to be disrupted by cisplatin, as well as to modulate chemotherapy toxicity. However, the precise role of intestinal microbiota in the pathogenesis of cisplatin hepatotoxicity remains unknown. METHODS: We compared the composition and function of gut microbiota between mice treated with and without cisplatin using 16S rRNA gene sequencing and via metabolomic analysis. For understanding the causative relationship between gut dysbiosis and cisplatin hepatotoxicity, antibiotics were administered to deplete gut microbiota and faecal microbiota transplantation (FMT) was performed before cisplatin treatment. RESULTS: 16S rRNA gene sequencing and metabolomic analysis showed that cisplatin administration caused gut microbiota dysbiosis in mice. Gut microbiota ablation by antibiotic exposure protected against the hepatotoxicity induced by cisplatin. Interestingly, mice treated with antibiotics dampened the mitogen-activated protein kinase pathway activation and promoted nuclear factor erythroid 2-related factor 2 nuclear translocation, resulting in decreased levels of both inflammation and oxidative stress in the liver. FMT also confirmed the role of microbiota in individual susceptibility to cisplatin-induced hepatotoxicity. CONCLUSIONS: This study elucidated the mechanism by which gut microbiota mediates cisplatin hepatotoxicity through enhanced inflammatory response and oxidative stress. This knowledge may help develop novel therapeutic approaches that involve targeting the composition and metabolites of microbiota.

Uterine corpus invasion in cervical cancer: a multicenter retrospective case-control study.

OBJECTIVE: To determine the accuracy of uterine corpus invasion (UCI) diagnosis in patients with cervical cancer and identity risk factors for UCI and depth of invasion. METHODS: Clinical data of patients with cervical cancer who underwent hysterectomy between 2004 and 2016 were retrospectively reviewed. UCI was assessed on uterine pathology. Independent risk factors for UCI and depth of invasion were identified using binary and ordinal logistic regression models, respectively. RESULTS: A total of 2,212 patients with cervical cancer from 11 medical institutions in China were included in this study. Of these, 497 patients had cervical cancer and UCI, and 1,715 patients had cervical cancer and no UCI, according to the original pathology reports. Retrospective review of the original pathology reports revealed a missed diagnosis of UCI in 54 (10.5%) patients and a misdiagnosis in 36 (2.1%) patients. Therefore, 515 patients with cervical cancer and UCI (160 patients with endometrial invasion, 176 patients with myometrial invasion < 50%, and 179 patients with myometrial invasion ≥ 50%), and 1697 patients with cervical cancer without UCI were included in the analysis. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI. These risk factors, except resection margin involvement, were independently associated with depth of UCI. CONCLUSIONS: UCI may be missed or misdiagnosed in patients with cervical cancer on postoperative pathological examination. Older age, advanced stage, tumor size, adenocarcinoma, parametrial involvement, resection margin involvement, and lymph node metastasis were independent risk factors for UCI and depth of UCI, with the exception of resection margin involvement.

Effect of pre-operative radiotherapy on long-term outcomes among women with Stage IB1 to IIB cervical squamous cell carcinoma.

OBJECTIVE: To compare long-term outcomes between pre-operative radiotherapy followed by open surgery and direct open surgery among women with Stage IB1-IIB cervical squamous cell carcinoma. METHODS: A multicenter retrospective cohort study among women with Stage IB1-IIB cervical squamous cell carcinoma who underwent open surgery either directly (SD group) or with pre-operative radiotherapy (PR group) in China 2004-2016. Five-year overall survival (OS) and disease-free survival (DFS) between the two groups were compared by Kaplan-Meier methods and multivariate Cox regression. RESULTS: Overall, 8385 women with Stage IB1-IIB were included (PR group, n = 447; SD group, n = 7938). Five-year OS and DFS was significantly lower in the PR than in the SD group (OS: 81.7% vs 91.6%, P < 0.001; DFS: 76.3% vs 86.7%, P < 0.001). As compared with direct surgery, pre-operative radiotherapy was an independent risk factor for 5-year OS (adjusted hazard raio [aHR], 1.75; 95% confidence interval [CI], 1.34-2.30) and DFS (aHR, 1.37; 95% CI, 1.09-1.73) by multivariate Cox regression. Sensitivity analyses confirmed the findings. CONCLUSION: Among women with Stage IB1-IIB cervical squamous cell carcinoma, outcomes were found to be worse for those undergoing pre-operative radiotherapy followed by open surgery than for those undergoing direct open surgery.

Influence of uterine corpus invasion on prognosis in stage IA2-IIB cervical cancer: A multicenter retrospective cohort study.

OBJECTIVE: To determine the associations between the presence and depth of uterine corpus invasion and survival in patients with cervical cancer. METHODS: Clinical data of patients with stage IA2-IIB cervical cancer who underwent radical hysterectomy between 2004 and 2016 were retrospectively reviewed. Uterine corpus invasion was identified from a review of uterine pathology. Independent prognostic factors for 5-year disease-free survival (DFS) and overall survival (OS) were identified using multivariate forward stepwise Cox proportional hazards regression models. RESULTS: A total of 1414 patients with stage IA2-IIB cervical cancer from 11 medical institutions in China were included. Retrospective review of the original pathology reports revealed a missed diagnosis of uterine corpus invasion in 38 (13.4%) patients and a misdiagnosis in 20 (1.8%) patients. Therefore, 284 patients with cervical cancer and uterine corpus invasion (90 [31.7%] patients had endometrial invasion, 105 [37.0%] patients had myometrial invasion <50%, and 89 [31.3%] patients had myometrial invasion ≥50%), and 1130 patients with cervical cancer without uterine corpus invasion were included in the analysis. The 5-year DFS and OS were significantly shorter for patients with uterine corpus invasion compared to patients with no uterine corpus invasion. Myometrial invasion ≥50% was an independent prognostic factor associated with decreased 5-year DFS (aHR, 2.307, 95% CI, 1.588-3.351) and 5-year OS (aHR, 2.736, 95% CI, 1.813-4.130), while myometrial invasion <50% or endometrial invasion had no effect on patient outcomes. CONCLUSIONS: Diagnosis of uterine corpus invasion is frequently missed. Myometrial invasion ≥50% within the uterine corpus was an independent factor associated with worse prognosis in patients with cervical cancer, while myometrial invasion <50% or endometrial invasion had no effect on outcomes.

Retrospective analysis of risk factors for low 1-minute Apgar scores in term neonates.

The current study was designed to investigate the perinatal risk factors for low 1-min Apgar scores in term neonates. We retrospectively analyzed the maternal and neonatal clinical data of 10,550 infants who were born through vaginal delivery from 37 weeks 0 days to 41 weeks 6 days of single gestation from January 2013 to July 2018. Because the 1-min Apgar score reflects neonatal status at birth, we analyzed the risk factors for low (score <7) 1-min Apgar scores through logistic regression. Among these 10,550 neonates, 339 (3.2%) had low (score <7) 1-min Apgar scores. Among them, 321 (94.7%) were admitted to the neonatology department for further observation or treatment. Multivariate analysis revealed that educational background, body mass index, gestational age, pathological obstetrics, longer duration of the second stage of labor, forceps delivery or vacuum extraction, neonatal weight, neonatal sex, and meconium-stained amniotic fluid were independent risk factors for 1-min Apgar scores <7. Neonates who had low 1-min Apgar scores were more frequently admitted to the neonatology department for further observation or treatment. Early detection of risk factors and timely intervention to address these factors may improve neonatal outcomes at birth and reduce the rate of admission to the neonatology department.

Retrospective analysis of risk factors for low 1-minute Apgar scores in term neonates

The current study was designed to investigate the perinatal risk factors for low 1-min Apgar scores in term neonates. We retrospectively analyzed the maternal and neonatal clinical data of 10,550 infants who were born through vaginal delivery from 37 weeks 0 days to 41 weeks 6 days of single gestation from January 2013 to July 2018. Because the 1-min Apgar score reflects neonatal status at birth, we analyzed the risk factors for low (score <7) 1-min Apgar scores through logistic regression. Among these 10,550 neonates, 339 (3.2%) had low (score <7) 1-min Apgar scores. Among them, 321 (94.7%) were admitted to the neonatology department for further observation or treatment. Multivariate analysis revealed that educational background, body mass index, gestational age, pathological obstetrics, longer duration of the second stage of labor, forceps delivery or vacuum extraction, neonatal weight, neonatal sex, and meconium-stained amniotic fluid were independent risk factors for 1-min Apgar scores <7. Neonates who had low 1-min Apgar scores were more frequently admitted to the neonatology department for further observation or treatment. Early detection of risk factors and timely intervention to address these factors may improve neonatal outcomes at birth and reduce the rate of admission to the neonatology department.