Para-aortic lymph node dissection with or without nerve-sparing in gynecological malignancies.

OBJECTIVE: Para-aortic lymph node dissection (PALND) is a widely used treatment that causes many complications. This study is to evaluate the efficacy and safety of nerve-sparing para-aortic lymph node dissection (NSPALND) by comparing it with conventional PALND in gynecological malignancies and to prove whether locating the superior hypogastric plexus (SHP) can help reveal the para-aortic nerves. METHODS: This is a retrospective study of the patients who underwent para-aortic lymphadenectomy from January 2020 to December 2022 at Zhejiang Cancer Hospital. All of them were divided into NSPALND and PALND groups according to whether or not nerve-sparing was performed. The surgical, functional and oncological outcomes were evaluated. RESULTS: There were 43 patients enrolled, of which, 20 patients underwent NSPALND and 23 patients underwent PALND. The para-aortic nerves were successfully revealed by locating the SHP in all 20 cases of NSPALND. The post-operative anal exhaust time in the NSPALND group was significantly shorter than that in the PALND group (2.5 vs. 4 days, p=0.006), and the incidence of acute intestinal obstruction in the NSPALND group was significantly lower than that in the PALND group (10% vs. 39%, p=0.029). There was no difference between the two groups in terms of catheterization duration, urinary retention, dysuria, as well as the number of lymph nodes removed and the para-aortic recurrence rate. CONCLUSION: NSPALND can significantly reduce the rate of acute intestinal obstruction and improve post-operative intestinal function. Locating the SHP and using it as an anatomical landmark to reveal the para-aortic nerves is feasible. Its exact clinical value needs to be further studied.

A multicenter noninferior randomized controlled study of sentinel lymph node biopsy alone versus sentinel lymph node biopsy plus lymphadenectomy for patients with stage I endometrial cancer, INSEC trial concept.

BACKGROUND: Up to the present time, there has remained a lack of strong evidence as to whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer. The traditional surgery for endometrial cancer includes pelvic lymphadenectomy and paraaortic lymph node resection, but complications often seriously affect patients' quality of life. Two randomized controlled trials with large samples have proved that lymphadenectomy does not improve the overall recurrence rate and survival rate of patients. On the contrary, it increases the incidence of complications and even mortality. The current trial is designed to clarify whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer patients with negative lymph nodes. METHODS: This study is a randomized, open-label, multicenter and non-inferiority controlled clinical trial in China. Potential participants will be patients with pathologically confirmed endometrial cancer at the Zhejiang Cancer Hospital, Jiaxing Maternity and Child Health Care Hospital, and the First Hospital of Jiaxing in China. The total sample size for this study is 722. Patients will be randomly assigned in a 1:1 ratio to two groups. Patients in one group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy ± paraaortic lymph node resection. Patients in the other group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy + pelvic lymphadenectomy ± paraaortic lymph node resection. The 3-year disease-free survival rate, overall survival rate, quality of life (use EORTC QLQ-C30 + QLQ-CX24), and perioperative related indexes of the two groups will be compared. RESULTS: We expect to find that for patients with early endometrial cancer, the 3-year disease-free survival rate following sentinel lymph node biopsy with indocyanine green combined with near-infrared fluorescence imaging is similar to that following lymphadenectomy. The operation time, as well as incidence of pelvic lymphocyst, lymphedema of lower limb, and edema of vulva in patients who only undergo sentinel lymph node biopsy are expected to be significantly lower than in patients who undergo lymphadenectomy. The quality of life of patients who undergo sentinel lymph node biopsy alone will be significantly better than that of patients who undergo lymph node dissection. CONCLUSION: This will prove that the prognosis of sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging is not inferior to that of sentinel lymph node biopsy plus lymphadenectomy for early stage endometrial cancer with negative nodal assessment intraoperatively. In addition, sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging results in fewer surgical complications and gives patients better quality of life. TRIAL REGISTRATION: chictr.org.cn, ChiCTR1900023161. Registered 14 May 2019, http://www.chictr.org.cn/edit.aspx?pid=38659&htm=4 .

Efficacy and Safety of Niraparib as First-Line Maintenance Treatment for Patients with Advanced Ovarian Cancer: Real-World Data from a Multicenter Study in China.

BACKGROUND: Poly (ADP-ribose) polymerase (PARP) inhibitors are a new maintenance therapy option for patients with ovarian cancer (OC). OBJECTIVE: To evaluate the efficacy and influencing factors of the novel PARP inhibitor niraparib for maintenance treatment of Chinese patients with advanced OC. PATIENTS AND METHODS: In this retrospective multicenter real-world study patients with advanced OC from 15 hospitals throughout China were enrolled. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included the time to treatment discontinuation and safety. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify possible risk factors for PFS, after which a prediction model was established to evaluate the likelihood of achieving an 18-month PFS. The relationship between the dose of niraparib and PFS was also evaluated. RESULTS: The PFS rates of 199 patients at 6, 12, 18, 24, and 30 months were 87.4%, 75.9%, 63.6%, 56.1%, and 51.8%, respectively. LASSO regression model revealed that only age < 65 years (P = 0.011), BRCA mutations (P < 0.001), and R0 status after cytoreductive surgery (P = 0.01) were significant factors associated with prolonged PFS times. Based on the LASSO logistic regression analysis, a clinical prediction formula was developed: - 2.412 + 1.396Age≥65yr + 2.374BRCAwt + 1.387R1 + 0.793Interval≥12w + 0.178BMI>24kg/m2 which yielded a cut-off value of 0.091, an area under the curve (AUC) of 0.839 (0.763-0.916), a sensitivity of 94.3%, and an accuracy of 78.5%. A nomogram was then built to visualize the results. The major treatment-emergent adverse events of ≥ grade 3 included a platelet count decrease (19.1%), white blood cell count decrease (15.1%), neutrophil count decrease (13.1%), and anemia (18.6%). The 18-month PFS rates in patients treated with 200 mg niraparib were somewhat higher than in patients treated with 100 mg after 3-months of therapy. CONCLUSIONS: For Chinese OC patients, niraparib, particularly at a 200 mg individual starting dose, was an effective therapy with easily manageable safety.

Maintenance therapy with poly (ADP-ribose) polymerase inhibitors is a new option for patients with ovarian cancer (OC) after they have received platinum-based chemotherapy to reduce the recurrence or relapse rates, but it remains unclear whether there are any changes in efficacy and safety when different starting doses of niraparib are administrated to Chinese patients, who typically have a bodyweight < 77 kg. We found that niraparib exhibited satisfactory efficacy with tolerable safety during maintenance therapy for advanced OC whether administered at 100 mg or 200 mg doses. We believe these regimens can serve as a valuable addition to the previous results of randomized controlled trials.

The preoperative platelet to neutrophil ratio and lymphocyte to monocyte ratio are superior prognostic indicators compared with other inflammatory biomarkers in ovarian cancer.

Background: Previous studies have suggested that the ratios of immune-inflammatory cells could serve as prognostic indicators in ovarian cancer. However, which of these is the superior prognostic indicator in ovarian cancer remains unknown. In addition, studies on the prognostic value of the platelet to neutrophil ratio (PNR) in ovarian cancer are still limited. Methods: A cohort of 991 ovarian cancer patients was analyzed in the present study. Receiver operator characteristic (ROC) curves were utilized to choose the optimal cut-off values of inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and PNR. The correlation of inflammatory biomarkers with overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier methods and log-rank test, followed by Cox regression analyses. Results: Kaplan-Meier curves suggested that LMR<3.39, PLR≥181.46, and PNR≥49.20 had obvious associations with worse RFS (P<0.001, P=0.018, P<0.001). Multivariate analysis suggested that LMR (≥3.39 vs. <3.39) (P=0.042, HR=0.810, 95% CI=0.661-0.992) and PNR (≥49.20 vs. <49.20) (P=0.004, HR=1.351, 95% CI=1.103-1.656) were independent prognostic indicators of poor RFS. In addition, Kaplan-Meier curves indicated that PLR≥182.23 was significantly correlated with worse OS (P=0.039). Conclusion: Taken together, PNR and LMR are superior prognostic indicators compared with NLR, PLR, and SII in patients with ovarian cancer.

SPP1 is a prognostic related biomarker and correlated with tumor-infiltrating immune cells in ovarian cancer.

BACKGROUND: Secreted phosphoprotein 1 (SPP1) plays a vital role in tumor progression of multiple cancer types However, it still awaits further exploration whether SPP1 is a bystander or an actual player in the modulation of immune infiltration in ovarian cancer. METHODS: In this study, the expression level of SPP1 was identified by Oncomine, GEPIA and TIMER databases, and the result of SPP1 immumohistochemical staining was acquired by The HPA database. The impact of SPP1 expression level on the clinical outcome of ovarian cancer patients were evaluated via Kaplan-Meier Plotter and PrognoScan dataset. Immune infiltration analyses were conducted using TIMER and TISIDB dataset. In addition, Functional enrichment analyses were performed with Metascape and GeneMANIA database. To verify these findings from the public database, the results were validated in a cohort of ovarian cancer patients. RESULTS: SPP1 was found to be overexpressed in ovarian tumor tissues and high SPP1 expression was correlated with shorter survivals. Notably, SPP1 expression was positively correlated with infiltrating levels of CD4 + T cells, CD8 + T cells, macrophages, neutrophils, and dendritic cells. Furthermore, SPP1 expression level showed strong correlation with diverse immune cells in ovarian cancer. Of note, functional enrichment analysis suggested that SPP1 was strongly correlated with immune response. CONCLUSIONS: These findings imply that SPP1 is correlated with prognosis and immune cell infiltrating, offering a new potential immunotherapeutic target in ovarian cancer. TRIAL REGISTRATION: Not applicable.

Radical surgery for stage IB2/IIA2 cervical cancer: A large retrospective study.

Background: We aimed to evaluate survival, complications, and prognostic factors in patients with IB2/IIA2 (FIGO 2009, bulky early-stage) cervical cancer (CC) who were primarily treated with radical surgery (RS). Methods: From January 2011 to January 2018, patients with stage IB2/IIA2 CC who underwent RS ± adjuvant therapy were enrolled and retrospectively evaluated. Survival was estimated using the Kaplan-Meier method. Significance was determined using the log-rank test. Multivariate regression analyses were performed to determine prognostic factors. Results: Of the 975 enrolled patients, 877 (89.9%) received adjuvant therapy. The median follow-up was 48 months, the 5-year overall survival (OS) was 85.9%, and the 5-year progression-free survival (PFS) rate was 80.8%. Multivariate analysis showed that histological type, pelvic lymph nodes, and para-aortic lymph nodes were independent prognostic factors for PFS and OS. Tumor diameter was also an independent prognostic factor with OS. Recurrent disease developed in 14.3% (140) of patients., including local, distant, and both recurrences in 55 (5.6%), 71 (7.3%), and 14 (1.4%) patients, respectively. Grade 3-4 short-term complications occurred in 196 (20.1%) patients, and long-term complications occurred in 86 (8.8%) patients. Short-term hematological complications occurred in 99 cases (10.2%). No significant differences in non-hematological complications were detected between the RS and RS + adjuvant therapy groups. Conclusions: RS followed by adjuvant therapy is a feasible and effective treatment for IB2/IIA2 CC, with a high 5-year survival rate and an acceptable incidence of complications. Positive pelvic lymph nodes and para-aortic abdominal lymph nodes significantly impact PFS and OS. Evaluation of lymph node status before surgery is important. RS is recommended for patients with negative lymph node metastasis.

Multi-symplectic integrator of the generalized KdV-type equation based on the variational principle.

The variational principle is used to construct a multi-symplectic structure of the generalized KdV-type equation. Accordingly, the local energy conservation law, the local momentum conservation law, and the Cartan form of the generalized KdV-type equation are given. An explicit multi-symplectic scheme for the generalized KdV equation based on the Fourier pseudo-spectral method and the symplectic Euler scheme is constructed. Through a numerical examination, the explicit multi-symplectic Fourier pseudo-spectral scheme for the generalized KdV equation not only preserve the discrete global energy conservation law and the global momentum conservation law with high accuracy, but show long-time numerical stability as well.

Preventative effect of celecoxib in dimethylbenz[a]anthracene-induced ovarian cancer in rats.

PURPOSE: The present study investigated the preventive effect of the cyclooxygenase (COX)-2 inhibitor, celecoxib, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced ovarian cancer in a rat model. METHODS: A diet containing celecoxib (1500 ppm) was started 2 weeks before the introduction of DMBA. DMBA-soaked cotton threads were surgically applied to induce ovarian cancer in female Wistar rats. Tumor growth and survival were observed for 24 weeks. RESULTS: During the study period, an overall tumor incidence of 97.5% was observed and 65% of tumors were ovarian adenocarcinoma. The celecoxib diet significantly reduced the incidence and size of DMBA-induced ovarian cancers and significantly improved survival of tumor-bearing rats. The preventive effect of celecoxib was associated with increased apoptosis. CONCLUSION: DMBA-induced ovarian cancer in rats recapitulates many pathophysiological features of the human counterpart. Our results provide supportive evidence that celecoxib has a preventive effect on development of ovarian cancer in a rat model.

Mental distress, quality of life and social support in recurrent ovarian cancer patients during active chemotherapy.

BACKGROUND: Anxiety and depression are common sources of mental distress experienced by ovarian cancer patients. The purpose of this study was to identify changes in levels of mental distress during active chemotherapy, to characterize the impact of these changes on quality of life (QOL), and to study the potential buffering effect of social support in recurrent ovarian cancer patients. METHODS: Anxiety and depression were assessed at baseline and three months after initiation of active chemotherapy using hospital anxiety and depression scale (HADS). QOL was evaluated at the same time points using European Organization for Research and Treatment [EORCT] 30-item core quality of life questionnaire (QLQ-C30) and QLQ-OV28. Social support was evaluated by perceived social support scale (PSSS) at baseline. RESULTS: Our results showed recurrent ovarian cancer patients had high rates of anxiety and depression. Levels of anxiety, but not depression, were significantly decreased following active chemotherapy. Notably, both anxiety and depression were significantly associated with poorer QOL on all functioning domains, global health and most symptom domains at both baseline and after chemotherapy. Social support was associated with improved mental state and several functioning and symptom domains of QOL. CONCLUSIONS: Our study reveals a high prevalence of mental distress and its profound detrimental impact on QOL in Chinese women with recurrent ovarian cancer. Social support is beneficial to alleviate mental distress and improve QOL.

Association of financial status and the quality of life in Chinese women with recurrent ovarian cancer.

BACKGROUND: Very few studies have examined the association between financial status and the quality of life (QOL) of patients with specific cancers. Ovarian cancer survivors frequently suffer repeat recurrence and subsequent treatment and, as a result, a significant added financial burden. Financial burdens disproportionally affect patients of low income. This study examines the association between financial status, based upon family income and expenses, and QOL in Chinese women with recurrent ovarian cancer. METHODS: We assessed baseline and follow-up (3-month) QOL of Chinese women with recurrent ovarian cancer using the European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30), and the Quality of Life Ovarian Cancer 28 Questionnaire (QLQ-OV28). Financial status was stratified based upon self-reported disposable income. Linear or logistic regression models were applied to determine the relationship between QOL in each financial status category, and key demographic and clinical factors. RESULTS: Among all 473 ovarian cancer patients, 123 of them met enrollment criteria were recruited to this study and completed baseline questionnaires; 95 of these patients completed the 3-month follow-up questionnaires. Our results showed that low financial status was significantly associated with worse QOL on all functioning domains and several symptom domains. QOL deteriorated during the follow-up. A significantly greater number of patients with low financial status experienced deteriorating QOL in several domains. Occupation and insurance type, two factors related to financial status, were significantly associated with QOL as well, but to a lesser extent. Education, recurrence interval, age and BMI were also significantly related to certain domains of QOL. CONCLUSIONS: Financial status is associated with QOL of Chinese women with recurrent ovarian cancer. These patients showed worsening QOL during active chemotherapy. Lower financial status is associated with a higher risk of deteriorating QOL in several domains.

Concomitant paclitaxel plus carboplatin and radiotherapy for high-risk or advanced endometrial cancer.

OBJECTIVE: The objective of this study was to evaluate the outcome and feasibility of concurrent chemotherapy with paclitaxel plus carboplatin and radiotherapy (RT) in patients with high-risk or advanced endometrial cancer. METHODS: A retrospective analysis of patients treated between January 2003 and December 2009 was conducted. Adjuvant therapy consisted of external beam radiation to the pelvis (45-48.6 Gy) and weekly administration of paclitaxel (40 mg/m(2)) plus carboplatin with an area under the curve of 2 administered intravenously during RT. Two further cycles of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve, 5), separated by 4 weeks, were administered at the end of RT for advanced stage disease. Para-aortic RT and/or vault brachytherapy were added at the discretion of the physicians. RESULTS: A total of 31 patients with a median age of 56 years (31-69 years) were evaluated. The majority had stage III disease (58%), and the most common histology was endometrioid adenocarcinoma (78%). All patients completed the planned RT. The median follow-up time was 64 months (12-86 months). Five patients' conditions progressed, and all 5 died of the disease. Most of the 5 patients were with serous histologic type and advanced stage disease. There was no local recurrence. The 2-, 3-, and 5-year progression-free survival rates were 87%, 84%, and 79%, respectively. The 2-, 3-, and 5-year overall survival rates were 94%, 87%, and 83%, respectively. Toxicity included grade 3/4 neutropenia in 45.2% of patients, gastrointestinal toxicity in 32.3% of patients, and grade 1/2 sensory neuropathy in 38.7% of patients. CONCLUSIONS: Concomitant paclitaxel plus carboplatin and radiation was feasible and well tolerated and resulted in excellent local-regional control. However, distant metastases continued to occur in more advanced-stage patients. This regimen appears reasonable to be tested for efficacy in randomized studies.

[Clinical significance of serum proteomic profiling before and after cervical cancer surgery].

OBJECTIVE: To investigate the value of serum proteomic profiling in cervical cancer detected pre-surgery and post-surgery. METHODS: Magnetic bead and matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect the serum samples from 54 cases with cervical cancer before and after surgery and 53 serum samples from healthy women. The results of spectra were analyzed by Biomarker Wizard software. RESULTS: Significant variation of proteomic profiling between pre-surgery and post-surgery were analyzed. There were 22 proteins with different mass/charge (M/Z) values significantly different (P < 0.01) at the M/Z value range from 1500 to 50 000, among of which relative content of proteins with M/Z 3981, 4290, and 28 066 in pre-surgery cervical cancer patients were higher than those in health women [(1.51 +/- 1.78)% vs (0.83 +/- 0.38)%, (2.70 +/- 2.19)% vs (1.72 +/- 0.91)%, (1.99 +/- 1.70)% vs (0.92 +/- 0.95)%; P < 0.01], while in the post-surgery patients, relative content of these three proteins significantly decreased to (0.59 +/- 0.45)%, (1.01 +/- 0.64)%, (0.54 +/- 0.37)%, respectively. But the relative content of another three proteins with M/Z 11 487, 11 529, and 11 678 were significantly increased in post-surgery patients [(0.38 +/- 1.41)% vs (2.74 +/- 3.67)%, (0.16 +/- 0.46)% vs (2.00 +/- 1.76)%, (1.02 +/- 1.67)% vs (7.71 +/- 9.46)%; P < 0.01]. CONCLUSION: Serum proteomic profiling could screen out the proteins which had significant variation between pre-surgery and post-surgery serum, of which with M/Z 3981, 4290, and 28 066 may be related with tumor burden, while with M/Z 11 487, 11 529, and 11 678 may be response to surgical stress.