Reviving peritoneal cytology: Exploring its role in endometrial cancer molecular classification.

OBJECTIVE: The prognostic significance of positive peritoneal cytology in endometrial cancer has long been debated. In 2009, the Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) removed cytology as a staging criterion from the endometrial cancer staging system. However, there is still evidence that positive peritoneal cytology may decrease survival among patients with endometrial cancer. The aim of this study was to determine the prognostic significance of positive peritoneal cytology among the different molecular subgroups. METHODS: This study included patients with endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Bern University Hospital, Switzerland, with molecular classification of the primary tumor and peritoneal cytology performed. RESULTS: A total, 250 patients with endometrial cancer were enrolled. Peritoneal cytology was assessed in 206 patients, of whom 24% were positive: 25% of the POLEmut, 16% of the MMRd, 41% of the p53abn, and 24% of the NSMP cases. The mean follow-up was 128.7 months. Presence of positive peritoneal cytology was associated with significantly decreased mean recurrence-free and overall survival in patients with p53abn (p = .003 and p = .001) and NSMP (p = .020 and p = .049) endometrial cancer. In multivariable Cox regression analysis, positive peritoneal cytology remained an independent predictor of recurrence (p = .033) and death (p = .008) in p53abn endometrial cancer patients. CONCLUSION: Positive peritoneal cytology is associated with worse oncologic outcomes in NSMP and p53abn endometrial cancer and remains an independent predictor of recurrence and death in patients with p53abn endometrial cancer.

Intrauterine manipulator during hysterectomy for endometrial cancer: a systematic review and meta-analysis of oncologic outcomes.

OBJECTIVE: This study aimed to assess the effects on oncologic outcomes of intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer. DATA SOURCES: A systematic literature search was performed by an expert librarian in multiple electronic databases from inception to January 31, 2023. STUDY ELIGIBILITY CRITERIA: We included all studies in the English language that compared oncologic outcomes (recurrence-free, cause-specific, or overall survival) between endometrial cancer patients who underwent total laparoscopic or robotic hysterectomy for endometrial cancer with vs without the use of an intrauterine manipulator. Studies comparing only peritoneal cytology status or lymphovascular space invasion were summarized for completeness. No selection criteria were applied to the study design. METHODS: Four reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled hazard ratios with 95% confidence intervals were estimated for oncologic outcomes using the random effect model. Heterogeneity was quantified using the I2 tests. Publication bias was assessed by funnel plot and Egger test. RESULTS: Out of 350 identified references, we included 2 randomized controlled trials and 12 observational studies for a total of 14 studies and 5,019 patients. The use of an intrauterine manipulator during hysterectomy for endometrial cancer was associated with a pooled hazard ratio for recurrence of 1.52 (95% confidence interval, 0.99-2.33; P=.05; I2=31%; chi square P value=.22). Pooled hazard ratio for recurrence was 1.48 (95% confidence interval, 0.25-8.76; P=.62; I2=67%; chi square P value=.08) when only randomized controlled trials were considered. Pooled hazard ratio for overall survival was 1.07 (95% confidence interval, 0.65-1.76; P=0.79; I2=44%; chi square P value=.17). The rate of positive peritoneal cytology or lymphovascular space invasion did not differ using an intrauterine manipulator. CONCLUSION: Intrauterine manipulator use during hysterectomy for endometrial cancer was neither significantly associated with recurrence-free and overall survival nor with positive peritoneal cytology or lymphovascular space invasion, but further prospective studies are needed.

Preoperative predictive factors for positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas: a retrospective study.

BACKGROUND: The clinical importance of positive peritoneal cytology results in patients with pancreatic ductal adenocarcinomas remains controversial. We evaluated the prognosis of these patients and the predictive preoperative risk factors for positive peritoneal cytology results. METHODS: We retrospectively reviewed patients who underwent curative-intent surgery at our institution between May 2010 and June 2020. Preoperative risk factors for positive peritoneal cytology results were identified using logistic regression analysis. A scoring model was constructed using the total number of significant independent predictors for positive peritoneal cytology results. RESULTS: Of 233 patients, 18 (7.7%) had positive peritoneal cytology results. The recurrence-free survival and cancer-specific survival were markedly worse in patients with positive peritoneal cytology results than in those with negative peritoneal cytology results (recurrence-free survival: 6.0 months vs. 16.6 months, p = 0.050; cancer-specific survival: 19.4 months vs. 47.5 months, p = 0.034). Tumor location (odds ratio: 3.760, 95% confidence interval: 1.099-11.818, p = 0.023), tumor size > 25 mm (odds ratio: 3.410, 95% confidence interval: 1.031-11.277, p = 0.046), preoperative serosal invasion (odds ratio: 5.193, 95% confidence interval: 1.099-24.531, p = 0.038), and preoperative carcinoembryonic antigen level > 5.6 ng/mL (odds ratio: 3.816, 95% confidence interval: 1.248-10.667, p = 0.019) were identified as significant independent predictive factors. Our predictive model's optimal cutoff and positive predictive values for positive peritoneal cytology results were 3 and 27.9%, respectively. CONCLUSIONS: The indications for curative-intent surgery should be considered carefully in patients with high-risk factors for positive peritoneal cytology results.

The Impact of Positive Peritoneal Cytology on the Survival Rates of Early-Stage-Disease Endometrial Cancer Patients: Systematic Review and Meta-Analysis.

Background and Objectives: The impact of positive peritoneal cytology has been a matter of controversy in early-stage endometrial cancer for several years. The latest staging systems do not take into consideration its presence; however, emerging evidence about its potential harmful effect on patient survival outcomes suggests otherwise. In the present systematic review and meta-analysis, we sought to accumulate current evidence. Materials and Methods: Medline, Scopus, the Cochrane Central Register of Controlled Trials CENTRAL, Google Scholar and Clinicaltrials.gov databases were searched for relevant articles. Effect sizes were calculated in Rstudio using the meta function. A sensitivity analysis was carried out to evaluate the possibility of small-study effects and p-hacking. Trial sequential analysis was used to evaluate the adequacy of the sample size. The methodological quality of the included studies was assessed using the Newcastle-Ottawa scale. Results: Fifteen articles were finally included in the present systematic review that involved 19,255 women with early-stage endometrial cancer. The Newcastle-Ottawa scale indicated that the majority of included studies had a moderate risk of bias in their selection of participants, a moderate risk of bias in terms of the comparability of groups (positive peritoneal cytology vs. negative peritoneal cytology) and a low risk of bias concerning the assessment of the outcome. The results of the meta-analysis indicated that women with early-stage endometrial cancer and positive peritoneal cytology had significantly lower 5-year recurrence-free survival (RFS) (hazards ratio (HR) 0.26, 95% CI 0.09, 0.71). As a result of the decreased recurrence-free survival, patients with positive peritoneal cytology also exhibited reduced 5-year overall survival outcomes (HR 0.50, 95% CI 0.27, 0.92). The overall survival of the included patients was considerably higher among those that did not have positive peritoneal cytology (HR 12.76, 95% CI 2.78, 58.51). Conclusions: Positive peritoneal cytology seems to be a negative prognostic indicator of survival outcomes of patients with endometrial cancer. Considering the absence of data related to the molecular profile of patients, further research is needed to evaluate if this factor should be reinstituted in future staging systems.

Prognostic significance of positive peritoneal cytology in endometrial carcinoma based on ESGO/ESTRO/ESP risk classification: A multicenter retrospective study.

OBJECTIVE: This study aimed to determine the prognostic significance of positive peritoneal cytology (PC) on endometrial carcinoma (EC) patients under the ESGO/ESTRO/ESP risk classification. METHODS: This study retrospectively analyzed EC patients from 27 medical centers in China from 2000 to 2019. Patients were divided into three ESGO risk groups: low-risk, intermediate-risk and high-intermediate risk, and high-risk groups. The covariates were balanced by using the propensity score-based inverse probability of treatment weighting (PS-IPTW). The prognostic significance of PC was assessed by Kaplan-Meier curves and multivariate Cox regression analysis. RESULTS: A total of 6313 EC patients with PC results were included and positive PC was reported in 384 women (6.1%). The multivariate Cox analysis in all patients showed the positive PC was significantly associated with decreased PFS (hazard ratio [HR] 2.20, 95% confidence interval [CI] 1.55-3.13, P < 0.001) and OS (HR 2.25, 95% CI 1.49-3.40, P < 0.001),and the Kaplan-Meier curves also showed a poor survival in the intermediate and high-intermediate risk group (5-year PFS: 75.5% vs. 93.0%, P < 0.001; 5-year OS: 78.3% vs. 96.4%, P < 0.001); While in the low-risk group, there were no significant differences in PFS and OS between different PC status (5-year PFS: 93.1% vs. 97.3%, P = 0.124; 5-year OS: 98.6% vs. 98.2%, P = 0.823); in the high-risk group, significant difference was only found in PFS (5-year PFS: 62.5% vs. 77.9%, P = 0.033). CONCLUSION: Positive PC was an adverse prognostic factor for EC, especially in the intermediate and high-intermediate risk patients. Gynecologic oncologists should reconsider the effect of positive PC on different ESGO risk groups.

Malignant peritoneal cytologic contamination with robotic hysterectomy for endometrial cancer.

BACKGROUND: Malignant peritoneal cytology in endometrial cancer (EC) is not considered an independent adverse prognostic factor for uterine-confined disease and is not a determinant factor in the International Federation of Gynecology and Obstetrics (FIGO) staging system. NCCN Guidelines still recommend obtaining cytologies. The aim of this study was to determine the prevalence of peritoneal cytologic contamination following robotic hysterectomy for EC. METHODS: Peritoneal cytology from the pelvis and diaphragm were obtained at the initiation of surgery, and from the pelvis only at the completion of robotic hysterectomy with sentinel lymph node mapping (SLNM). Cytology specimens were evaluated for the presence of malignant cells. Pre- and post-hysterectomy cytology results were compared, and pelvic contamination was defined as conversion from negative to positive cytology following surgery. RESULTS: 244 patients underwent robotic hysterectomy with SLNM for EC. Pelvic contamination was identified in 32 (13.1%) cases. In multivariate analysis, pelvic contamination was associated with >50% myometrial invasion, tumor size >2 cm, lymphovascular space invasion (LVSI), and lymph node metastasis. There was no association with FIGO stage or histology subtypes. CONCLUSIONS: Malignant peritoneal contamination occurred during robotic surgery for EC. Large lesions (>2 cm), deep invasion (>50%), LVSI, and lymph node metastasis were each independently associated with peritoneal contamination. Whether or not peritoneal contamination increases risk for disease recurrence should be studied in larger series, including an evaluation of patterns of recurrence and the potential impact of adjuvant therapies. Until the clinical impact of peritoneal contamination during hysterectomy for EC is better understood, methods to reduce peritoneal contamination are warranted.

Efficacy of chemotherapy versus surgery as initial treatment for gastric cancer with positive peritoneal cytology.

BACKGROUND: The prognosis of gastric cancer (GC) patients with positive peritoneal cytology (CY1) without other distant metastasis is poor, and there are no standard treatment strategies. Our study aimed to compare the survival outcomes of CY1 GC patients receiving chemotherapy or surgery as initial treatment. METHODS: From February 2017 to January 2020, clinical and pathological data of patients diagnosed with CY1 GC without other distant metastasis in the Peking University Cancer Hospital was reviewed. Patients were divided into two groups: chemotherapy-initial group and surgery-initial group. In chemotherapy-initial group, patients received preoperative chemotherapy initially. According to the treatment response, the patients were divided into three subgroups: conversion gastrectomy group, palliative gastrectomy group, and further systematic chemotherapy group. In surgery-initial group, patients underwent gastrectomy followed by postoperative chemotherapy. RESULTS: A total of 96 CY1 GC patients were included with 48 patients in each group. In chemotherapy-initial group, preoperative chemotherapy yielded an objective response rate of 20.8% and disease control rate of 87.5%. Conversion to CY0 after preoperative chemotherapy was obtained in 24 (50%) patients. The median overall survival was 36.1 months in chemotherapy-initial group and 29.7 months in surgery-initial group (p = 0.367). The median progression-free survival was 18.1 months in chemotherapy-initial group and 16.1 months in surgery-initial group (p = 0.861). The 3-year overall survival rates were 50.0% and 47.9%, respectively. In chemotherapy-initial group, twenty-four patients who converted to CY0 by preoperative chemotherapy and received surgery obtained a significantly better prognosis. The median overall survival was still not reached in these patients. CONCLUSION: There was no significant difference in survival outcomes between chemotherapy-initial group and surgery-initial group. CY1 GC patients who converted to CY0 by preoperative chemotherapy and received radical surgery could obtain a favorable long-term prognosis. Further investigation should focus on preoperative chemotherapy to eliminate peritoneal cancer cell. TRIAL REGISTRATION: This study is retrospectively registered.

Significance of positive peritoneal cytology for recurrence and survival in patients with endometrial cancer.

AIM: This study aims to examine the association between malignant peritoneal cytology and prognosis in women with endometrial cancer. METHODS: We retrospectively analyzed the records of patients with endometrial cancer who underwent surgery with intraoperative peritoneal cytology at our hospital between January 1988 and December 2012. All results were reclassified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) system, and the relation between intraoperative peritoneal cytology results and recurrence and prognosis was examined. RESULTS: Of the 908 patients analyzed, 205 (22.6%) had positive peritoneal cytology. Patients with positive peritoneal cytology had significantly lower rates of recurrence-free survival (RFS) and overall survival (OS) than those in the negative cytology group (both p < 0.001). Subgroup analysis of patients with FIGO stage I/II showed significantly lower RFS in the positive-cytology group (p = 0.005), but there was no significant difference in OS (p = 0.637). In the patients with FIGO stage III/IV or patients classified as "high risk," the RFS and OS were significantly lower in the positive-cytology group (both p < 0.001). Cox regression analysis identified positive peritoneal cytology as a significant predictor of recurrence in patients with FIGO stage I/II disease. CONCLUSIONS: Patients with positive peritoneal cytology for endometrial cancer have a high risk of recurrence, regardless of histopathologic type or FIGO stage. Peritoneal cytology has already been removed from the 2009 FIGO classification of endometrial cancer, but it may deserve reconsideration.

Preoperative risk factors for positivity of peritoneal lavage cytology in patients with pancreatic ductal adenocarcinoma in the era of neoadjuvant therapy.

BACKGROUND: The preoperative risk factors for positive peritoneal lavage cytology (CY) are unknown, especially in patients who received neoadjuvant therapy. In addition, the optimal indications for staging laparoscopy (SL) are still unclear. The aim of this study was to investigate the preoperative risk factors of CY positivity in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection and to determine the optimal indications for SL. METHODS: We retrospectively analyzed 493 patients with PDAC, including 356 treated with upfront surgery and 137 treated with neoadjuvant chemotherapy (NAC). The preoperative risk factor for CY positivity was investigated along with stratification according to NAC. RESULTS: Among the 493 patients, 36 (7.3%) were CY-positive. The CY-positive frequency in patients who received and did not receive NAC was 9 (6.6%) and 27 (7.6%), respectively. In the multivariate analyses, no independent preoperative predictive factor was found in patients who received NAC, whereas body and tail PDAC were identified as an independent risk factor for CY positivity in patients who did not receive NAC. CONCLUSIONS: The preoperative risk factors of CY-positive PDAC are body and tail PDAC in 356 patients who did not receive NAC. However, there is no useful predictive factor for CY positivity in patients treated with NAC. Based on these results, it was difficult to determine the optimal indication for SL especially in NAC cases.

Hormonal therapy or chemotherapy for early-stage, low-grade endometrial cancer with malignant peritoneal cytology: A comparative effectiveness study.

OBJECTIVE: To examine trends, characteristics, and outcomes related to hormonal therapy (HT) or chemotherapy (CT) use for early-stage, low-grade endometrial cancer with malignant peritoneal cytology (MPC). METHODS: This is a comparative effectiveness study querying the National Cancer Database from 2010 to 2017. Study population was 2730 women with stage I grade 1-2 endometrioid endometrial cancer who had MPC at primary hysterectomy. Patients were stratified based on postoperative therapy as: CT (n = 348, 12.7%), HT (n = 112, 4.1%), and neither two (n = 2270, 83.2%). Outcome measures included (i) trends and characteristics related to adjuvant therapy, assessed with a multivariable logistic regression model, and (ii) overall survival (OS) assessed with a multivariable Cox proportional hazards regression model. RESULTS: The number of women who received HT (2.7% to 4.5%) or no adjuvant systemic therapy (81.8% to 84.4%) increased while CT use decreased (15.5% to 11.1%)(P = 0.04). In a multivariable analysis, HT use was associated with older age, more recent year of diagnosis, grade 1 lesions, treatment at academic/research facilities, performance of minimally invasive surgery, no lympho-vascular space invasion, and absence of radiotherapy compared to CT use (P < 0.05). Neither HT (adjusted-hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.27-1.40) nor CT (aHR 1.33, 95% CI 0.92-1.93) were associated with OS compared to no adjuvant systemic therapy. In the low-risk group (stage IA, grade 1-2 tumors, and no lympho-vascular space invasion; n = 1453), 69 (4.7%) women received HT and 117 (8.1%) received CT. OS was similar across the three groups (P = 0.89). CONCLUSION: There was an increasing utilization of HT and decreasing utilization of CT as adjuvant therapy for early-stage, low-grade endometrial cancer with MPC. These two adjuvant therapies were not associated with short-term OS compared to neither two.

Prognostic significance of positive peritoneal cytology in endometrial cancer patients.

Although peritoneal cytology has been shown to be an independant predictor of survival in endometrial cancer, the present international federation of gynaecology and obstetrics (FIGO) staging system does not involve it for risk stratification. This work aimed to assess the prognostic importance of PPC (positive peritoneal cytology) in endometrial cancer patients. The medical profiles of uterine carcinoma patients were reviewed who were referred to Khatam-al- Anbia and Bahman hospital within 2010-2019. The factors possibly affecting peritoneal fluid cytology in all patients were analysed. There was a considerable association between survival and the number of lymph nodes involvement (95% CI = 2.5 - 12.51, OR = 5.59, p < .001), stage 3 (95% CI = 2.95-22.10, OR = 7.12, p < .001), stage IV (95% CI = 2.14 - 30.09, OR = 8.04, p < .001), Grade (95% CI = 4.4-47.7, OR = 14.54, p < .001). Positive peritoneal cytology was revealed in our study, as an independent prognostic factor in patients with endometrial cancer. Impact statementWhat is already known on this subject? Peritoneal cytology is one of the independent risk factors for poor survival for endometrial cancer, but international federation of gynaecology and obstetrics (FIGO) staging system does not involve it for risk stratification.What do the results of this study add? Positive peritoneal cytology was revealed in our study, as an independent prognostic factor in patients with endometrial cancer.What are the implications of these findings for clinical practice and/or further research? It is recommended peritoneal cytology for future FIGO staging reviews. Till now, peritoneal washings need to be still regarded as a key part for precise risk-stratification.

Re-thinking the prognostic significance of positive peritoneal cytology in endometrial cancer.

BACKGROUND: Whether abnormal peritoneal cytology (PC) is an independent prognostic factor in endometrial cancer (EC) remains controversial. This study aimed to re-think the prognostic significance of PC in not only all EC patients but also in various subgroups with similar clinicopathological and biological characteristics. METHODS: EC patients who underwent primary surgery of at least a hysterectomy and were pathologically diagnosed with EC in four hospitals affiliated with the Jikei University School of Medicine were retrospectively reviewed. The prognostic significance of PC was evaluated with univariate and multivariate analyses in the entire cohort and subgroups stratified by surgical stages (early/advanced stages), tumor types (types 1/2), and risk classifications (low/intermediate/high). RESULTS: Of 1963 EC cases, 1616 met the inclusion criteria. Positive PC was identified as an adverse prognostic factor in analyses of all EC cases and in all subgroup analyses stratified by surgical stages and tumor types. In survival curve comparisons, the progression-free survival (PFS) and disease-specific survival in early-stage patients with positive PC were clearly located between those of stage II patients with negative PC and stage III patients. In the subgroup analyses stratified by risk classification in early-stage EC, positive PC was related to poorer PFS in the intermediate- and high-risk groups but not in the low-risk group. CONCLUSION: PC status was an independent prognostic factor of EC in all stages and tumor types. Early PC-positive cases, except for the low-risk group, may be recommended for upstaging and should be carefully managed compared with PC-negative cases.

Trends in peritoneal cytology evaluation at hysterectomy for endometrial cancer in the United States.

OBJECTIVE: The collection of a peritoneal cytologic sample at the time of surgery for endometrial cancer has traditionally been an important part of surgical staging. In 2009, the International Federation of Gynecology and Obstetrics revised the cancer staging schema for endometrial cancer and removed peritoneal cytology from the staging criteria. The current National Comprehensive Cancer Network guidelines and the International Federation of Gynecology and Obstetrics organization, however, recommend evaluation of peritoneal cytology at the time of hysterectomy. This study examined population-based trends, characteristics, and outcomes of peritoneal cytologic sampling for endometrial cancer surgery following the 2009 staging revision in the United States. METHODS: This is a retrospective observational study querying the Surveillance, Epidemiology, and End Results Program to examine women with stage I-III endometrial cancer who underwent hysterectomy from 2010 to 2017. Trends, characteristics, and survival associated with peritoneal cytologic evaluation at the time of hysterectomy were assessed in multivariable analysis and with propensity score weighting. RESULTS: Among 62,809 women who underwent hysterectomy, 43,873 (69.9%) had peritoneal cytologic evaluation at surgery and 18,936 (30.1%) did not. Utilization of peritoneal cytologic evaluation decreased from 75.5% to 64.9% during the study period (P < 0.001). In multivariable analysis, more recent year of surgery was independently associated with a decreased likelihood of performance of peritoneal cytology (adjusted-odds ratio of peritoneal cytology evaluation in 2017 versus 2010 0.56, 95% confidence interval [CI] 0.52-0.60). Peritoneal cytologic evaluation at the time of hysterectomy was associated with improved all-cause mortality (hazard ratio in the whole cohort 0.94, 95%CI 0.89-0.99; and hazard ratio in endometrioid histology 0.90, 95%CI 0.84-0.97). CONCLUSION: Performance of peritoneal cytologic sampling has gradually decreased following the 2009 staging revision in the United States. Our study suggests that peritoneal cytology evaluation at hysterectomy may be associated with improved survival in certain tumor groups.

Clinico-pathological significance of suspicious peritoneal cytology in endometrial cancer.

BACKGROUND AND OBJECTIVES: Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer. METHODS: A population-based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I-III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine-Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology. RESULTS: Suspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution-hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29-2.20, p < 0.001) and all-cause mortality (adjusted-HR: 1.55, 95% CI: 1.27-1.90, p < 0.001) compared with negative peritoneal cytology. Sensitivity analysis demonstrated that suspicious peritoneal cytology had discrete overall survival improvement compared with malignant peritoneal cytology in a propensity score weighting model (HR: 0.85, 95% CI: 0.72-0.99, p = 0.049). CONCLUSION: Our study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer.

Comparison of prognostic impact between positive intraoperative peritoneal and lavage cytologies in colorectal cancer.

BACKGROUND: The prognostic value of positive intraoperative peritoneal cytology and lavage cytology, including the differences in their prognostic impact, in colorectal cancer is controversial. We aimed to investigate the prognostic values of positive peritoneal cytology and lavage cytology findings for colorectal cancer and compare their prognostic impact. METHODS: We retrospectively evaluated 592 clinical stage II-IV colorectal cancer patients who underwent peritoneal cytology (n = 225) or lavage cytology (n = 367) between November 1993 and December 2018. The prognostic factors for cancer-specific survival were identified, and the differences in cancer-specific survival were examined between the patients. RESULTS: The cytology-positive rate was 10.8% (64/592), 17.8% (40/225), and 6.5% (24/367) in the overall, peritoneal cytology, and lavage cytology groups, respectively. Both positive peritoneal cytology (hazard ratio: 2.196) and lavage cytology (hazard ratio: 2.319) were independent prognostic factors. The peritoneal cytology-positive group showed significantly poorer cancer-specific survival than the cytology-negative group (5-year: 3.5% vs. 59.5%; 10-year: 3.5% vs. 46.1%, p < 0.001). Similar results were obtained for lavage cytology (5-year: 14.1% vs. 73.9%; 10-year: 4.7% vs. 63.5%, p < 0.001). The cancer-specific survival was not significantly different between the peritoneal cytology-positive and lavage cytology-positive groups (p = 0.058). Both positive peritoneal and lavage cytology were associated with poorer cancer-specific survival across all colorectal cancer stages. CONCLUSIONS: Positive peritoneal and lavage cytology are associated with worse cancer-specific survival in colorectal cancer. The prognostic impact was comparable between positive lavage and peritoneal cytology. Thus, cytology should be a standard assessment modality for colorectal cancer.

Prognostic significance of peritoneal cytology in low-risk endometrial cancer: comparison of laparoscopic surgery and laparotomy.

BACKGROUND: There is uncertainty surrounding the prognostic value of peritoneal cytology in low-risk endometrial cancer, especially in laparoscopic surgery. The objective of this retrospective study is to determine the prognostic significance of positive peritoneal cytology among patients with low-risk endometrial cancer and to compare it between laparoscopic surgery and conventional laparotomy. METHODS: From August 2008 to December 2019, all cases of pathologically confirmed stage IA grade 1 or 2 endometrial cancer were reviewed at Osaka Medical College. Statistical analyses used the Chi-square test and the Kaplan-Meier log rank. RESULTS: A total of 478 patients were identified: 438 with negative peritoneal cytology (232 who underwent laparotomy and 206 who undertook laparoscopic surgery) and 40 with positive peritoneal cytology (20 who underwent laparotomy and 20 who received laparoscopic surgery). Survival was significantly worse among patients with positive peritoneal cytology compared to patients with negative peritoneal cytology. However, there was no significant difference among patients with negative or positive peritoneal cytology between laparoscopic surgery and laparotomy. CONCLUSION: This retrospective study suggests that, while peritoneal cytology is an independent risk factor in patients with low-risk endometrial cancer, laparoscopic surgery does not influence the survival outcome when compared to laparotomy.

Is Diagnostic Hysteroscopy Safe for the Investigation of Type II Endometrial Cancer? A Retrospective Cohort Analysis.

STUDY OBJECTIVE: Although hysteroscopy (HSC) can be used for assessing the uterine cavity in women with suspected endometrial cancer (EC), it remains controversial as a procedure because it can potentially enhance the metastatic spread of cancer cells. Moreover, it is important to assess this hypothesis for type II EC, a more aggressive phenotype that usually presents with endometrial atrophy and has worse prognosis. Thus, we aimed to assess the prevalence of positive peritoneal cytology result in women with type II EC who underwent HSC as a diagnostic tool and to determine the factors associated with patient relapse/survival. DESIGN: Retrospective cohort analysis (2002-2017). SETTING: Tertiary, academic hospital. PATIENTS: One hundred twenty-seven women with type II EC. INTERVENTIONS: Diagnostic HSC (HSC) (n = 43) or dilation/curettage (D&C) (n = 84). MEASUREMENTS AND MAIN RESULTS: Primary end point was the frequency of positive peritoneal cytology result. Survival curves were projected using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis with hazard ratio (HR) and 95% confidence intervals (CIs) were calculated to assess the factors related with the disease-free survival (DFS) and the disease-specific survival (DSS). Advanced cancer stage and greater vascular invasion appeared more frequently in the D&C group (p = .008 and p = .04, respectively). Positive peritoneal cytology result was present in 2 of 43 (4.6%) women following HSC and in 9 of 84 (10.7%) following D&C (p = .22). DFS and DSS curves did not statistically differ between the groups. Multivariate analysis for DFS revealed that advanced cancer stage (III and IV) (HR = 4.67; 95% CI, 2.34-9.34; p <.001) and advanced age (HR = 1.08; 95% CI, 1.04-1.13]; p <.001) were the factors associated with relapse. For DSS, advanced age (HR = 1.08; 95% CI, 1.05-1.12; p <.001), cancer stage III/IV (HR = 3.95; 95% CI, 2.18-7.15; p <.001), and vascular invasion (HR = 2.47; 95% CI, 1.34-4.54; p = .004) increased the risk of mortality. CONCLUSION: Diagnostic HSC did not increase the rate of positive peritoneal cytology result at the time of surgical staging in this cohort of women with type II EC and is probably as safe as D&C.

Prognostic impact of combined progression index based on peritoneal grading regression score and peritoneal cytology in peritoneal metastasis.

AIMS: The peritoneal regression grading score (PRGS) and peritoneal cytology (PC) assess response to chemotherapy in peritoneal metastasis (PM) in a setting of palliative treatment by pressurized intraperitoneal aerosol chemotherapy (PIPAC). Progression has been defined as an increase of PRGS between first and third PIPAC procedures (iPRGS). iPRGSand positive peritoneal cytology were not associated with prognostic impact. These results may be explained by a lack of statistical power. Also, it is not known whether the mean or the highest PRGS among taken peritoneal biopsies bears the highest clinical value. We therefore conducted the largest prospective study to investigate the prognostic impact of PGRS, PC, and their combination, designated as combined progression index (CPI). METHODS AND RESULTS: Patients with PM who underwent >3 PIPAC (n = 112) between December 2016 and February 2019 were prospectively included. A significant difference in OS and PFS according to CPI (used highest value of PRGS) was found (OS: CPI-, 83.3, 95% CI [49.8; NA] vs. CPI+, 48.1, 95% CI [38.5; 66.4] months; and PFS (respectively, 59.7, 95% CI [43.0; 96.0] vs. 33.7, 95% CI [30.4; 44.2] months). PRGS or PC had no independent prognostic impact. CPI+ was an independent predictor of worse prognosis, in OS (HR = 5.24, 95% CI [2.07; 13.26]), and PFS (HR = 4.41, 95% CI [1.40; 13.88]). CONCLUSIONS: The CPI based on highest PRGS and PC was found to be independently associated with a worse prognosis for OS and for PFS in the setting of peritoneal metastasis. These results indicate that it should be of interest to systematically take peritoneal fluid for cytological examination and to implement the CPI in the therapeutic decision-making process in the context of PIPAC.

Malignant peritoneal cytology and increased mortality risk in stage I non-endometrioid endometrial cancer.

OBJECTIVE: To examine the survival of women with stage I non-endometrioid endometrial cancer with malignant peritoneal cytology. METHODS: A retrospective observational cohort study was conducted to examine the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I serous, clear cell, carcinosarcoma, undifferentiated, and mixed endometrial cancer with known peritoneal cytology results at hysterectomy were examined (N = 4506). Propensity score inverse probability of treatment weighting was used to balance the measured covariates, and survival outcomes were assessed according to peritoneal cytology results. RESULTS: Malignant peritoneal cytology was reported in 401 (8.9%) women. In multivariable analysis, older age, serous histology, and large tumors were associated with an increased likelihood of malignant peritoneal cytology (all, P < 0.05). In a propensity score weighted model, malignant peritoneal cytology was associated with a nearly two-fold increase in all-cause mortality risk compared to negative peritoneal cytology (5-year rates, 63.4% versus 80.2%, hazard ratio 2.18, 95% confidence interval 1.78-2.66). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in old and young age groups, serous, clear cell, carcinosarcoma, and mixed histology groups, stage T1a disease, and staged and unstaged cases, but not for stage T1b disease. Difference in 5-year overall survival rates between the malignant and negative peritoneal cytology groups was particularly large among those with clear cell histology (24.0%), stage T1a disease (19.4%), aged >78 years (18.2%), and serous tumors (17.6%). CONCLUSION: Malignant peritoneal cytology can be prevalent in stage I non-endometrioid endometrial cancer. Our study suggests that malignant peritoneal cytology is a prognostic factor for decreased survival in stage I non-endometrioid endometrial cancer.

Free cancer cells in gastric cancer - methods of detection, clinical and prognostic importance (meta-analysis).

Gastric cancer (GC) is one of the most common malignant cancers worldwide. Intraperitoneal dissemination is the typical mechanism of the formation of metastases in GC. The diagnosis of the presence of intraperitoneal free cancer cells (IFCCs) is treated equally to the M (metastasis) category according to the 8th edition of the TNM classification by the American Joint Committee on Cancer. IFCCs are cells which have detached from the primary tumour through exfoliation into the peritoneal cavity. The source of IFCCs may be iatrogenic due to improper surgical technique during resection of the tumour and may lead to intraperitoneal dissemination. Cytological examination of peritoneal lavage is considered as a gold standard in the confirmation of the presence of IFCCs; however, its sensitivity is very low. In order to increase the sensitivity and reliability of the examination, molecular biology techniques should be applied. In the case of detection of the presence of IFCCs in patients with GC, the patient should be qualified for chemotherapy, or possibly the use of hyperthermic intraperitoneal chemotherapy should be considered.