Prognostic analysis of peritoneal washing cytology during interval debulking surgery in advanced ovarian cancer.

BACKGROUND: Interval debulking surgery (IDS) following neoadjuvant chemotherapy is a treatment option for advanced ovarian cancer. Optimal surgery is required for better survival; however, while peritoneal washing cytology (PWC) has been identified as a prognostic factor, its comprehensive assessment during IDS remains unexplored. Therefore, we aimed to evaluate PWC efficacy during IDS, alongside other factors including residual disease and the modeled cancer antigen 125 (CA-125) ELIMination rate constant K (KELIM), by retrospectively reviewing the medical records of 25 patients with advanced ovarian cancer underwent neoadjuvant chemotherapy and IDS between January 2017 to June 2023. RESULTS: Twelve (48.0%) patients were PWC-positive, and the remainder were PWC-negative. PWC was performed at laparotomy during IDS, after which five (41.7%) PWC-positive and four (30.8%) PWC-negative patients received bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, for maintenance treatment. Four (33.3%) PWC-positive and 10 (76.9%) PWC-negative patients received poly adenosine diphosphate (ADP)-ribose polymerase inhibitors. In patients who received bevacizumab and poly ADP-ribose polymerase inhibitors, overall survival and progression-free survival did not significantly differ between those who were PWC-positive and PWC-negative (p = 0.27 and 0.20, respectively). Progression-free survival significantly differed between those with favorable and unfavorable CA-125 KELIM (p = 0.02). Multivariate analysis indicated that optimal surgery and favorable CA-125 KELIM were associated with better progression-free survival (p < 0.01 and 0.02, respectively), with only optimal surgery associated with better overall survival (p = 0.04). CONCLUSIONS: A positive PWC at IDS was not associated with survival in advanced ovarian cancer. Our findings indicate that although PWC status at IDS should be one of the factors determining survival in patients with advanced ovarian cancer, recent improvements in maintenance therapy may make the combination of CA-125 KELIM and PWC status a more useful prognostic factor in selecting treatment after IDS. Further studies are needed to validate these results, highlighting the potential importance of maintenance treatment after IDS and the need for further research to validate the clinical significance of a positive PWC.

Prognostic impact of peritoneal washing cytology in patients with biliary tract cancer.

PURPOSE: To elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC). METHODS: Clinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis. RESULTS: Among the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19-9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively). CONCLUSION: Patients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.

Evaluating staging laparoscopy indications for pancreatic cancer based on resectability classification and treatment strategies for patients with positive peritoneal washing cytology.

Introduction: The prognosis of pancreatic ductal adenocarcinoma (PDAC) in patients with positive peritoneal washing cytology (CY1) is poor. We aimed to evaluate the results of staging laparoscopy (SL) and treatment efficacy in CY1 patients based on a resectability classification. Methods: We retrospectively reviewed 250 patients with PDAC who underwent SL before the initial treatment between 2017 and 2023 at the University of Toyama. Results: The breakdown of cases by resectability classification was resectable (R):borderline resectable (BR):unresectable locally advanced (UR-LA) = 131:48:71 cases. The frequency of CY1 increased in proportion to the degree of local progression (R:BR:UR-LA = 20:23:34%), but the frequencies of liver metastasis or peritoneal dissemination were comparable (R:BR:UR-LA = 6.9:6.3:8.5%). Most CY1 patients received gemcitabine along with nab-paclitaxel therapy. The CY-negative conversion rates (R:BR:UR-LA = 70:64:52%) and conversion surgery rates (R:BR:UR-LA = 40:27:9%) were inversely proportional to the degree of local progression.Comparing H0P0CY1 factors for each classification, patients with H0P0CY1 had significantly more pancreatic body or tail carcinoma and tumor size ≥32 mm in R patients, whereas in BR patients, duke pancreatic monoclonal antigen type 2 (DUPAN-2) ≥ 230 U/mL was a significant factor. In contrast, no significant factors were observed in UR-LA patients. Conclusion: The CY1 rates, CY-negative conversion rates, and conversion surgery rates varied according to local progression. In the case of R and BR, SL could be considered in patients with pancreatic body or tail carcinoma, large tumor size, or high DUPAN-2 level. In UR-LA, SL might be considered for all patients.

Predictive impacts of peritoneal washing cytology for surgical resection-intended pancreatic cancer cases: Establishment of planned staging laparoscopy criteria.

BACKGROUND: Staging laparoscopy (SL) has been advocated for pancreatic cancer, mainly to evaluate the peritoneal washing cytology (CY) status, which seems to impact the prognosis of pancreatic cancer. To establish an optimal treatment strategy for CY positive (CY+) pancreatic cancer cases, real-world clinical data about CY status-depending surgical outcomes should be accumulated. METHODS: Peritoneal washing samples were collected from 183 consecutive patients who could be classified as either resectable or borderline resectable (BR) pancreatic cancer between January 2012 and December 2020. Correlations between the CY status and other clinicopathological parameters with the recurrence patterns and survival outcomes were examined. In addition, we analyzed several risk factors for the CY+ status and attempted to identify the patient population that may benefit most from SL. RESULTS: A total of 24 of the 183 patients were CY+. Peritoneal recurrence occurred more frequently in CY+ cases than in CY- cases (29% vs. 6%, p < .001) and median survival time after surgery was significantly shorter in CY+ cases than in CY- cases (28.5 months vs. 67.5 months; p < .001). In detail, almost all CY+ patients among curative resection-intended cases had either elevated preoperative serum CA19-9 levels (≥250 U/mL) or DUPAN-2 levels (≥150 U/mL). Significant predictive factors of CY positivity were BR status (p = .028) and serum CA19-9 level exceeding 250 U/mL (p = .008). CONCLUSION: CY status was identified as an independent prognostic factor, and SL examination should be recommended, especially for patients with risk factors for CY positivity, such as BR cancer and elevated serum CA19-9 levels.

Efficacy of staging laparoscopy for resectable pancreatic cancer on imaging and the therapeutic effect of systemic chemotherapy for positive peritoneal cytology.

BACKGROUND: The frequency and prognosis of positive peritoneal washing cytology (CY1) in resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. The objective of this study was to identify the clinical implications of CY1 in R-PDAC and staging laparoscopy (SL). METHODS: We retrospectively analyzed 115 consecutive patients with R-PDAC who underwent SL between 2018 and 2022. Patients with negative cytology (CY0) received radical surgery after neoadjuvant chemotherapy, while CY1 patients received systemic chemotherapy and were continuously evaluated for cytology. RESULTS: Of the 115 patients, 84 had no distant metastatic factors, 22 had only CY1, and nine had distant metastasis. Multivariate logistic regression revealed that larger tumor size was an independent predictor of the presence of any distant metastatic factor (OR: 6.30, p = .002). Patients with CY1 showed a significantly better prognosis than patients with distant metastasis (MST: 24.6 vs. 18.9 months, p = .040). A total of 11 CY1 patients were successfully converted to CY-negative, and seven underwent conversion surgery. There was no significant difference in overall survival between patients with CY0 and those converted to CY-negative. CONCLUSION: SL is effective even for R-PDAC. The prognosis of CY1 patients converted to CY-negative is expected to be similar to that of CY0 patients.

The prognostic impact of peritoneal washing cytology for otherwise resectable extrahepatic cholangiocarcinoma patients.

The clinical importance of peritoneal washing cytology (PWC) for cholangiocarcinoma patients remains unclear. The clinical data of 137 extrahepatic cholangiocarcinoma patients who received PWC and curative surgery were retrospectively analyzed. Among the 137 patients analyzed, five (3.6%) had positive PWC, and 132 (96.4%) had negative PWC. The median survival time in patients with negative PWC was 6.45 years, and the overall 1-, 2-, and 5-year survival rates were 86.5%, 75.3%, and 51.6%, respectively. The median survival time in patients with positive PWC was 2.56 years, and the overall 1-, 2-, and 5-year survival rates were 60.0%, 60.0%, and 40.0%, respectively. A multivariate analysis revealed that positive lymph node metastasis (P < 0.001), positive perineural invasion (P = 0.014) and no use of adjuvant chemotherapy (P < 0.001), but not positive PWC were independently associated with a worse overall survival. In conclusion, surgery and subsequent chemotherapy might be a therapeutic option for cholangiocarcinoma patients with positive PWC.

Prognostic impact of intraoperative peritoneal cytology after neoadjuvant therapy for potentially resectable pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is considered a potential approach to improve survival for patients with pancreatic adenocarcinoma (PA). The objective of this study was to identify the clinical implications of washing peritoneal cytology (CY) status after NAT. METHODS: Between 2005 and 2016, 151 consecutive patients with resectable (R)/borderline resectable (BR) PA underwent NAT with intention of subsequent resection at our institution. Of them, 13 and 123 patients underwent pancreatectomies with positive (CY+) and negative (CY-) cytology, respectively, while the remaining 15 patients did not undergo resection due to gross metastases at laparotomy. The clinicopathological factors influencing overall survival were clarified by the uni- and multivariate analyses. RESULTS: The postoperative overall survival (OS) and disease-free survival (DFS) were markedly worse in patients who underwent resection with CY+, compared with those who were CY- (median OS, 14.8 m vs 30.8 m, p = 0.026, and median DFS 6.0 m vs 15.1 m, p = 0.008). According to the resectability by NCCN guidelines, CY+ indicates worse prognosis than CY- in R-PA patients (mOS: 30.1 m vs 71.1 m: p = 0.080). Similarly, in BR-PA patients, CY+ showed the significantly worse prognosis than CY- (mOS: 13.8 m vs 24.5 m: p = 0.048), which prognosis is comparable with patients who did not undergo resection. The multivariate analysis revealed that resectability, CY status and the induction of adjuvant therapy were significant predictors of postoperative OS (p = 0.007: Hazard ratio 2.264, 0.040:2.094 and 0.002:3.246, respectively). CONCLUSIONS: CY+ is a significant predictor of poorer prognosis in PA patients after NAT. The subsequent pancreatectomies with CY+ after NAT do not contribute to prolonged survival.

Prognostic indicators in pancreatic cancer patients undergoing total pancreatectomy.

PURPOSE: To evaluate the long-term outcomes of total pancreatectomy in a modern cohort of pancreatic cancer patients and to establish whether any factors identified prior to pancreatic resection were related to poor survival. METHODS: We analyzed, retrospectively, patients who underwent total pancreatectomy for pancreatic cancer between 2007 and 2016. The short- and long-term outcomes were investigated and Cox regression analysis was used to evaluate the prognostic factors identified before resection. RESULTS: The subjects were 49 patients with a mean age of 65 years, who underwent total pancreatectomy in our hospital during the study period. Peritoneal washing cytology was performed in 48 patients, with positive results in 4 (8.3%). There was no 30-day mortality. The median overall survival was 22.5 months, with a 5-year survival rate of 28.5%. Univariate analyses of the pre-resection variables revealed that overall survival was associated with tumor location, resectability classification, maximum standardized uptake value of positron emission tomography, the preoperative carbohydrate antigen 19-9 level, and peritoneal washing cytology status. Multivariate analysis revealed that positive peritoneal washing cytology status and the maximum standardized uptake value were independent predictors of poor survival. CONCLUSION: Total pancreatectomy for pancreatic cancer is appropriate for selected patients, but peritoneal washing cytology and positron emission tomography should be performed preoperatively.

Prognostic impact of intraoperative peritoneal cytology in interval debulking surgery for pelvic high-grade serous carcinoma.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine whether peritoneal washing cytology (PWC) during interval debulking surgery (IDS) could predict the prognosis of patients with pelvic high-grade serous carcinoma (HGSC) achieving R0 status. METHODS: Between January 2007 and May 2018, 110 patients with ovarian/tubal/primary peritoneal HGSC received platinum-based neo-adjuvant chemotherapy, followed by IDS at National Cancer Center Hospital, Japan. All the patients achieved R0 debulking status, defined as no macroscopic residual tumor in the peritoneal cavity at the completion of IDS. PWC was performed before debulking during IDS. The survival outcomes were compared between the PWC-positive and PWC-negative groups. RESULTS: The median progression free survival (PFS) for the entire cohort was 17 months (range, 5-133 months). The median PFS for the PWC-positive group was significantly shorter than that of the PWC-negative group (16 vs 19 months, HR 2.04, 95% CI 1.22-3.41, P-value < 0.01). Increased risk of progression was observed on both univariate and multivariate analyses, including age and FIGO stage (HR 2.28; 95% CI 1.35-3.84, P < 0.01). CONCLUSIONS: The positive PWC during IDS was found to predict earlier disease recurrence in patients with pelvic HGSC achieving R0 status. As performing PWC during IDS becomes standard practice, prospective validation should be conducted in the future.

Negative peritoneal washing cytology during interval debulking surgery predicts overall survival after neoadjuvant chemotherapy for ovarian cancer.

OBJECTIVE: Optimal debulking in interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) has been reported as a prognostic factor for patients with ovarian cancer. However, the identification of microscopic residual disease (MRD) using visualization and palpation is subjective. Peritoneal washing cytology (PWC) during IDS is an easy-to-implement, objective approach for assessing disease status, although its clinical relevance and association with MRD is not known. The aim of this study was to evaluate the efficacy of PWC during IDS. METHODS: In total, 164 patients diagnosed with ovarian cancer at our institution were retrospectively evaluated, including 64 who had received NAC. Seventeen patients had undergone an exploratory laparotomy followed by NAC, while the remaining patients were diagnosed based on imaging, peritoneal cytology, and tumor markers. The PWC was performed before intraperitoneal observation at laparotomy during IDS. RESULTS: NAC-treated patients had stage III-IV disease. IDS was performed in 78.1% of NAC-treated patients. Seventeen patients (26.6%) were PWC-negative and 33 patients (51.6%) were PWC-positive. Fourteen patients (21.9%) had progressive disease and were ineligible for IDS. The median overall survival of the PWC-negative, PWC-positive, and non-IDS groups was 47, 18, and 5 months, respectively. The differences were significant (p<0.01). PWC was an independent prognostic factor in the multivariate Cox regression analysis (p<0.001). CONCLUSION: PWC during IDS may be a prognostic factor for NAC-treated patients with ovarian cancer. PWC may be more useful than visualization and palpation in IDS for determining the presence of MRD.

Cleaved caspase-3 expression is a potential prognostic factor for endometrial cancer with positive peritoneal cytology.

INTRODUCTION: Positive peritoneal cytology (PPC) in endometrial cancer remains a controversial topic. Cleaved caspase-3 (CC3) and Ki-67 are excellent markers of apoptotic and proliferating cells, respectively. The objective of this study was to determine the significance of CC3 and Ki-67 expression in peritoneal cytology samples as prognostic factors for endometrial cancer with PPC. METHODS: Sixty endometrial cancer specimens with PPC alone were divided into 51 endometrioid tumours (43 endometrioid carcinomas and eight carcinomas with squamous differentiation) and nine non-endometrioid tumours (two serous carcinomas, three clear cell carcinomas and four carcinosarcomas). CC3 and Ki-67 expression in peritoneal cytology samples were immunocytochemically assessed and correlated with disease-free survival (DFS) and overall survival (OS). RESULTS: Expression levels of CC3 and Ki-67 were not associated with any clinicopathological parameter. Patients with non-endometrioid tumours had significantly shorter DFS (P = .001) and OS (P = .001). Low CC3 expression (CC3Low ) was significantly associated with shorter OS (P = .02), but not DFS (P = .13). Multivariate analysis showed that non-endometrioid histology and CC3Low were independent prognostic factors. However, Ki-67 expression was not associated with survival. When endometrioid and non-endometrioid tumours were assessed separately, CC3Low was significantly associated with shorter DFS (P = .002) and OS (P = .002) in patients with non-endometrioid tumours. CONCLUSIONS: Our results suggest that CC3Low in peritoneal cytology samples is a poor prognostic factor in patients with endometrial cancers, especially non-endometrioid tumours. Immunocytochemical analysis of CC3 expression could potentially facilitate identification of patients with high-risk endometrial cancer with PPC.

Negative peritoneal washing cytology during interval debulking surgery predicts overall survival after neoadjuvant chemotherapy for ovarian cancer / 부인종양

OBJECTIVE: Optimal debulking in interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) has been reported as a prognostic factor for patients with ovarian cancer. However, the identification of microscopic residual disease (MRD) using visualization and palpation is subjective. Peritoneal washing cytology (PWC) during IDS is an easy-to-implement, objective approach for assessing disease status, although its clinical relevance and association with MRD is not known. The aim of this study was to evaluate the efficacy of PWC during IDS. METHODS: In total, 164 patients diagnosed with ovarian cancer at our institution were retrospectively evaluated, including 64 who had received NAC. Seventeen patients had undergone an exploratory laparotomy followed by NAC, while the remaining patients were diagnosed based on imaging, peritoneal cytology, and tumor markers. The PWC was performed before intraperitoneal observation at laparotomy during IDS. RESULTS: NAC-treated patients had stage III–IV disease. IDS was performed in 78.1% of NAC-treated patients. Seventeen patients (26.6%) were PWC-negative and 33 patients (51.6%) were PWC-positive. Fourteen patients (21.9%) had progressive disease and were ineligible for IDS. The median overall survival of the PWC-negative, PWC-positive, and non-IDS groups was 47, 18, and 5 months, respectively. The differences were significant (p < 0.01). PWC was an independent prognostic factor in the multivariate Cox regression analysis (p < 0.001). CONCLUSION: PWC during IDS may be a prognostic factor for NAC-treated patients with ovarian cancer. PWC may be more useful than visualization and palpation in IDS for determining the presence of MRD.

Prognostic significance of intraoperative peritoneal washing cytology for patients with potentially resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The prognostic significance of intraoperative peritoneal washing cytology (IPWC) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the treatment strategy for PDAC patients with positive cytology has not been established. OBJECTIVES: The objective of this study was to evaluate the clinical significance of IPWC in PDAC patients. METHODS: This study included a retrospective cohort of 166 patients with curatively resected PDAC who underwent IPWC. RESULTS: Overall, 17 patients (10%) had positive cytology (CY+), and 149 (90%) patients were negative (CY-). Tumor location in the pancreatic body and/or tail and pancreatic anterior capsular invasion were independent predictors of a CY+ status (P = 0.012 and 0.041, respectively). The initial recurrence occurred at the peritoneum with a significantly higher frequency in CY+ patients (50%) than in CY- patients (12%) (P = 0.003). The median overall survival (OS) for CY+ patients was 12 months. The OS rates at 1 and 3 years were significantly higher for CY- patients (75.1% and 35.3%, respectively) versus CY+ patients (47.1% and 17.6%, respectively; P = 0.012). However, one CY+ patient survived for 66 months, and another two CY+ patients have survived for more than three years after surgery without evidence of peritoneal recurrence. In the multivariate analysis, the independent predictors of OS were a CY+ status, lymph node metastasis, and adjuvant chemotherapy. CONCLUSIONS: This study demonstrates that positive IPWC predicts early peritoneal recurrence and a poor prognosis for PDAC patients. However, a small but not insignificant subset of CY+ patients with PDAC may avoid peritoneal carcinomatosis.

Prognosis and treatment of patients with positive peritoneal cytology in advanced gastric cancer.

Positive peritoneal cytology in gastric cancer is classified as M1 disease by the 7(th) Edition of American Joint Committee on Cancer staging system. With the introduction of laparoscopy and peritoneal washing cytology in the staging of gastric cancer a new category of patients has been identified. These are patients with no macroscopic peritoneal metastases but with peritoneal cytology positive (P0C1). Prognosis and treatment of such patients represent a controversial issue. We evaluate the state of the art of staging system in gastric cancer and discuss standardisation in staging and treatment procedures. There is still a lack of uniformity in the use of laparoscopy with peritoneal cytology in clinical decision making and in the surgical treatment for gastric cancer. Survival of this patient subset remains poor. Multimodal therapies and new therapeutic strategies are required to improve the survival of these patients.

A Prospective Study on the Significance of Peritoneal Washing Cytology as a Diagnostic Modality in Colorectal Cancer

PURPOSE: Free intraperitoneal cancer cells exfoliated from a tumor are considered to be responsible for peritoneal dissemination. Therefore, microscopic evaluation of cells washed from the peritoneal cavity during surgery for various intraabdominal malignancies has been used to detect subclinical intraperitoneal metastases from these tumors. The purposes of this study were to detect intraperitoneal free cancer cells at the time of surgery by using peritoneal washing cytology in colorectal cancer and to evaluate their diagnostic significance. METHODS: During the 29-month period from January 2000 through May 2002, 149 randomly selected patients with primary colorectal cancer without evidence of gross peritoneal metastasis underwent peritoneal washing cytologic analysis before surgical manipulation of the tumor. Peritoneal washing cytology was compared with the pre-existing prognostic factors. RESULTS: Positive peritoneal washing for free cancer cells was found in 19 of 149 patients (12.8%). This positivity was significantly correlated with histologic grade (P=0.002), serosal invasion (P=0.025), lymph node metastasis (P=0.034), Astler-Coller classification (P=0.008), recurrence (P<0.001), and 5-year survival (P<0.001). Cancer-specific survival was significantly associated with histologic grade (P=0.025), peritoneal washing cytology (P<0.001), lymph node metastasis (P<0.001), recurrence (P<0.001), and stage (P= 0.010) in the multivariate analysis. CONCLUSIONS: The presence of free cancer cells was predictive of survival and was an independent prognostic factor. This information may be useful in stratifying patients with colorectal cancer for therapeutic trials, such as intraperitoneal chemotherapy.

Differential Diagnosis of Ovarian Mucinous, Serous, and Endometrioid Adenocarcinoma in Peritoneal Washing Cytology / 대한세포병리학회지

This study presents the cytologic features of peritoneal washings, with particular emphasis on the cytologic discrimination among serous, mucinous, and endometrioid adenocarcinoma of the ovary. We selected histologically confirmed 27 cases of peritoneal washing : 8 cases of serous cystadenocarcinomas, 5 cases of mucinous cystadenocarcinomas, and 14 cases of endometrioid adenocarcinomas. The most frequent cytologic pattern of three tumors was clusters. Ball pattern was found in serous cystadenocarcinoma(36%) and acinar pattern in endometrioid adenocarcinoma (36%). Mucinous adenocarcinoma showed mucoid background(100%) and endometrioid adenocarcinoma revealed inflammatory background(43%). The cytoplasmic vacuoles were noted in 80%, 13%, and 43% of mucinous, serous, and endometrioid adenocarcinoma, respectively. The endometrioid adenocarcinoma showed prominent nucleoli(64%). In conclusion, the cytologic findings of mucinous cystadenocarcinoma were different from that of serous and endometrioid carcinomas, such as mucoid background, abundant cytoplasm with vacuolated cytoplasm, and peripherally located cytoplasm. Although endometrioid carcinoma showed acinar pattern and prominent nucleoli, the differential diagnosis between serous cystadenocarcinoma and endometrioid adenocarcinoma in peritoneal washing cytology was not always possible.