Peritoneal Lavage Cytology Research Articles

Peritoneal washing in gynecological neoplasias

ABSTRACT Introduction and objective: Peritoneal washing cytology is part of pathological staging of adenocarcinomas of the endometrium and ovary. The objective of this study was to verify the prevalence of cytology positive for malignancy in patients diagnosed with adenocarcinoma of the endometrium or ovary, as well as to verify the association between the positive cytology and the variables age of the patient, histological type of the neoplasm and degree of tumor differentiation. Method: A retrospective and prospective cross-sectional study was carried out through the analysis of peritoneal washing cytology reports and the anatomopathological reports of 43 patients diagnosed with ovarian or endometrial adenocarcinoma, provided by the Pathology Center of Curitiba. Results: In relation to endometrial adenocarcinoma, the prevalence of positive cytologies was 7%. Neither the degree of tumor differentiation (p = 1) nor age (p = 0.233) demonstrated association with such positivity. In relation to ovarian adenocarcinoma, the prevalence of positive cytologies was 20%. The degree of tumor differentiation showed a significant positive association with this positivity (p = 0.044). Age did not show association (p = 0.804). It was not possible to verify association with the histological type of neoplasms due to non-applicability of the statistical test. Conclusion: The prevalence of peritoneal lavage cytology positive for malignancy was 7% in endometrial adenocarcinoma and 20% in ovarian adenocarcinoma. Only the degree of tumor differentiation of ovarian adenocarcinomas showed a significant association with peritoneal washing positivity.

Combined Aggressive Distal Gastrectomy and Double-Tract Reconstruction for Palliation of Incurable Locally Invasive Distal Gastric Cancer With Gastric Outlet Obstruction

Objective:To evaluate combined aggressive distal gastrectomy (ADG) and double-tract (DT) reconstruction (ADGDTR) for palliative treatment of gastric cancer with gastric outlet obstruction (GOO).Summary of Background Data:An effective standard palliation procedure has not been identified for patients with incurable gastric cancer.Methods:I retrospectively evaluated patients presenting to my clinic with GOO secondary to locally invasive distal gastric cancer between March 1996 and March 2011. Following a complete workup, patients underwent ADGDTR. ADG included the gastric tumor in whole or in part. DT reconstruction consisted of gastrojejunostomy, jejunoduodenostomy, and jejunojejunostomy.Results:In the enrolled patients (n = 7; 5 male; mean age, 71 years [range, 60–83 years]), preoperative comorbidities included anemia (7), diabetes mellitus (2), hepatic cirrhosis (1), cardiac ischemia (1), and Parkinson disease (1). The lesion invaded the pancreas in all patients, and the transverse mesocolon, liver, and mesentery were each involved in 1 patient. Metastatic disease affected the lymph nodes in 5 patients, liver in 1, and peritoneal cavity in 4. Peritoneal lavage cytology was positive in 3 patients and untested in 4. The mean operation time was 207 minutes (range, 150–295 minutes), and mean blood loss was 290 g (range, 110–480 g). Six patients had no postoperative complications, but 1 died of abdominal sepsis. The mean length of hospitalization was 43 days (range, 28–73 days), and mean survival was 8.3 months (range, 2–22 months). Six patients tolerated a low-residue or regular diet postoperatively.Conclusions:ADGDTR provided effective, low-risk palliation and long-term oral ingestion in patients with incurable, locally invasive distal gastric cancer with GOO.

Prognostic influence of endoscopic ultrasound-guided fine needle aspiration in IPMN-derived invasive adenocarcinoma

BackgroundEndoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for mucinous cystic neoplasm of the pancreas carries a potential risk of inducing peritoneal tumor cell dissemination. We investigated the diagnostic yield and safety of EUS-FNA-based cytology of cells obtained from the pancreatic invasion site of intraductal papillary-mucinous neoplasm-derived adenocarcinoma (IPMC).MethodsWe included 22 surgically resected IPMCs and 84 pancreatic ductal adenocarcinomas (PDACs). Among the IPMC cases, 14 did not undergo EUS-FNA before surgical resection. The diagnostic yield of EUS-FNA was compared between IPMC and PDAC. Additionally, prognosis (relapse-free and overall survival time after resection) and the rate of peritoneal dissemination were compared among IPMC with EUS-FNA, IPMC without EUS-FNA, and PDAC. A survival analysis was performed using the Kaplan-Meier method and log-rank test.Results(EUS-FNA diagnosis) There were no significant differences in the number of needle passages (PDAC 2.5 vs. IPMC 2.0 passages, P = 0.84) or puncture route (stomach/duodenum: 2/6 vs. 45/39, P = 0.29). However, the correct diagnosis rate was significantly higher in PDAC (92.9%) than in IPMC (62.5%) (P = 0.03). No procedure-related adverse events occurred. Peritoneal lavage cytology performed during the operation was negative in all cases. (Prognosis) Among IPMC with EUS-FNA, IPMC without EUS-FNA, and PDAC, there were no significant differences in relapse-free survival (21.0 vs. 22.4 vs. 12.5 months, respectively; P = 0.64) or overall survival time (35.5 vs. 53.1 vs. 35.9 months, respectively; P = 0.42), and peritoneal dissemination was detected during the observation period in 25%, 28.5%, and 21.4% cases, respectively (P = 0.82).ConclusionEven though a correct diagnosis was more difficult to obtain in IPMC than in PDAC, IPMC allows specimens to be obtained without influencing the rate of recurrence and prognosis.

Multidisciplinary therapy for scirrhous gastric cancer: a retrospective analysis and proposal of new treatment strategy.

BackgroundScirrhous gastric cancer (SGC) is highly invasive and metastatic because of its interactions with stromal cells, such as fibroblasts and macrophages, and extracellular matrix, leading to a higher incidence of peritoneal metastasis (PM) than other gastric cancers (GCs). Taxane-based intraperitoneal chemotherapy (IPC) is a promising therapy for PM. We retrospectively analyzed outcomes of multidisciplinary therapies that included IPC for SGC.Patients and therapyOf 1,679 GC patients treated between 1990 and 2012, we analyzed 119 patients who underwent multidisciplinary therapy for SGC. Patients without PM received gastrectomy with lymphadenectomy and resection of involved adjacent organs followed by intraoperative IPC using cisplatin. Patients with PM received chemotherapy using fluorouracil, with or without methotrexate plus IPC using cisplatin before 2000, and S-1 plus IPC using paclitaxel or docetaxel since 2000.ResultsOf the 119 patients, 73 (61%) had PM and 63 (53%) had positive peritoneal lavage cytology. Of the 89 gastrectomy patients, 30 (34%) had macroscopic residual tumors (R2). Of the patients treated since 2000, 66 (100%) received S-1 plus taxanes and 44 patients (67%) received taxane-based IPC. Median survival time was significantly longer in the post-2000 group (22.8 months) than in the pre-2000 group (9.5 months). In univariate analysis, lavage cytology, PM, taxane-based IPC, gastrectomy, and R2 resection were significant prognostic factors. However, only R2 resection was an independent prognostic factor in multivariate analysis (hazard ratio: 5.53, 95% CI: 2.05–14.93).ConclusionAs use of taxane-based IPC is not an independent prognostic factor, new multidisciplinary therapies are necessary to avoid R2 resections.

Role of positive peritoneal lavage cytology in carcinoma gall bladder: a prospective observational study of 60 patients with the preoperative diagnosis

Introduction: Positive peritoneal lavage cytology ( PLC) in patients with carcinoma stomach is considered M1 disease according to AJCC classification (7th edition, 2010). Status of PLC positivity in carcinoma gall bladder (CGB) is untested yet. Method: The study included 60 patients who underwent treatment in PGIMER, Chandigarh, India (June 2015–July 2016). After staging laparoscopy (SL), abdomen was explored and 50ml of normal saline instilled in the peritumoral region, right paracolic gutter and pelvis. The lavage fluid was aspirated, mixed with an anticoagulant and spun to obtain a sediment that was subjected to Liquid Based Cytology. Papanicolaou and May Grunwald Giemsa slides were studied for malignant cells. During SL, if metastatic, lavage was done laparoscopically. When resectable, patients underwent R0 resection. Results: There were 25 resectable, 2 unresectable, 22 metastatic and 11 cases of xanthogranulomatous cholecystitis. 6 out of 49 CGB patients had positive PLC ( 12.2%).1 patient had resectable G3pT2N0M0 adenocarcinoma, 1 had unresectable celiac lymph nodal metastasis and 4 had peritoneal metastasis on SL. The median disease- specific survival for metastatic disease was 4 months. The same for resected population (negative PLC) was not reached. The disease-free survival of the only resected patient with positive PLC was 5 months, comparable to that of metastatic patients. The survival difference between patients with positive and negative PLC was not significant. Conclusion: Although positive PLC may suggest advanced disease, the correlation between PLC and survival or disease stage is not statistically significant yet.

Prognostic factors for cytology-positive gastric cancer

Positive peritoneal lavage cytology for gastric carcinoma cells (CY1) is considered distant metastasis and is classified as Stage IV. However, patients with CY1 comprise a heterogeneous population, and their prognosis varies greatly. The prognostic factors for gastric cancer patients with CY1 were retrospectively reviewed. The participants were 80 gastric cancer patients with CY1 in our institution encountered between 2005 and 2017. Prognostic factors were analyzed using univariate and multivariate analyses. The operative procedure was distal gastrectomy for 30 patients, total gastrectomy for 27 patients, staging laparoscopy for 10 patients, gastrojejunostomy for 8 patients, and probe laparotomy for 5 patients. Other distant metastases were recognized in 36 patients. A multivariate analysis revealed that other distant metastases were the strongest independent risk factor for the overall survival (p < 0.0001). When the cohort was limited to CY1 patients without other distant metastases, cN2-3 (p = 0.01), the prognostic nutritional index (PNI) < 40 (p = 0.02) and Type 4 (p = 0.03) were independent risk factors according to a multivariate analysis. The survivals of patients with cN2-3 or PNI < 40 after gastrectomy were equivalent to those with other distant metastases, as assessed by log-rank analyses. The prognoses of CY1 gastric cancer patients with cN2-3 or PNI < 40 were poor, even after gastrectomy.

Adjuvant Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in resected high-risk colon cancer patients - study protocol for the PIPAC-OPC3 Trial. A prospective, controlled phase 2 Study.

BackgroundPeritoneal metastasis (PM) is the second most common site of recurrence in colon cancer (CC) patients and accounts for approximately one-third of all recurrences. Patients with T4 or intraperitoneal perforated colon cancers have an increased risk of developing PM, and since manifest PM is difficult to treat, high-risk patients should be offered prophylactic treatment. Here, we propose a study of adjuvant oxaliplatin administered as pressurized intraperitoneal aerosol chemotherapy (PIPAC OX) in patients with high-risk colon cancer (T4, perforated tumors, ovarian metastasis).MethodsPIPAC-OPC3 CC is a non-randomized, non-blinded phase 2 cohort study designed to treat high-risk colon cancer patients with adjuvant PIPAC-directed therapy. Based on an expected 90 % peritoneal recurrence-free survival with adjuvant PIPAC against the estimated 75 % without, 60 patients are needed (α: 0.05, power: 0.8). Eligible patients will receive two PIPAC treatments with oxaliplatin (92 mg/m2) at 4–6 week intervals. During laparoscopy, the peritoneum is biopsied at two locations, and peritoneal lavage with 500 mL of saline and laparoscopic ultrasound is performed. The patients are screened for adverse medical events and surgery-related complications after each PIPAC procedure. After the second PIPAC procedure, the patients will be examined in the outpatient clinic and followed with CT scans 12, 24 and 36 months after resection. The primary outcome of the PIPAC-OPC3 CC trial is to evaluate if PIPAC-directed adjuvant therapy can reduce the risk of PM. Secondary outcomes include the number of conversions from positive to negative peritoneal lavage cytology after one PIPAC procedure, completion rate of two adjuvant PIPAC treatments, toxicity and complication rate and recurrence-free and overall survival rates after 1, 3 and 5 years.ResultsIt is expected that PIPAC-directed adjuvant therapy can provide an absolute risk reduction of 15 % regarding the development of PM in high-risk colon cancer patients, and that this may result in increased survival rates. We expect that free intraperitoneal tumor cells (FITC) may be detected by peritoneal lavage performed just prior to the administration of PIPAC-directed therapy, and that this treatment may convert FITC-positive patients to a FITC-negative status.ConclusionsThis study may provide important knowledge to be used in designing additional studies on PIPAC in the adjuvant setting of other primary cancers.Trial registrationClinicalTrials.gov Identifier NCT03280511 (2017-09-12). European Clinical Trials Database (EudraCT) 2017-002637-37.

Significance of peritoneal lavage cytology based on genetic signatures in gastric cancer

The Journal of Cancer Metastasis and Treatment is an open access journal focused on cancer metastasis and treatment, including the occurrence, development, progression, metastasis, and treatment of oncologic disease. It covers basic, translational and clinical research related to cancer cell biology, genomics, precision medicine, oncology internal medicine, radiotherapy and radiology, obstetrics and gynecology, pediatrics, surgery, hematology, neurooncology, etc.

The impact of pre-operative chemotherapy in patients with peritoneal lavage cytology positive or localized peritoneum metastasis for gastric cancer: A multicenter retrospective study.

95 Background: Peritoneal lavage cytology of positive and localized peritoneum metastasis of gastric cancer (GC) are defined as CY1 and P1 in the 14th edition of the Japanese Classification of GC. Patients (pts) with CY1 and/or P1 have poor prognosis after removing all macroscopically visible disease by standard gastrectomy followed by S1. The aim of this study was to investigate the efficacy of pre-operative chemotherapy (Pre-Cx) in patients with CY1 and/or P1. Methods: We retrospectively reviewed the GC pts who were diagnosed to have CY1 and/or P1 at 34 institutions participating in the Stomach Cancer Group of Japan Clinical Oncology Group between 2007 and 2012. Inclusion criteria were: no distant metastasis other than CY1 or P1, no prior treatment for GC. The subjects were divided to two groups according to treatment strategy with/without Pre-Cx before surgery. In the Pre-Cx group, status of CY and P was diagnosed by laparoscopy before and after Pre-Cx, and indication of surgical resection was decided by each physician. Results: A total of 824 pts were collected from 34 institutions. Of the 713 eligible pts, 150 pts received Pre-Cx (Pre-Cx group) and 563 pts underwent surgery followed by Cx (Post-Cx group). Proportions of P0CY1/P1CY0/P1CY1 were 69/12/19% and 69/17/14% in the Pre- and Post-Cx. Cx regimen for Pre-Cx were S1 plus cisplatin/ docetaxel and cisplatin plus S1/others (n=90/37/23). In the Pre-Cx, 57 (38%) pts who achieved P0CY0 after Pre-Cx showed better survival than the remaining 92 pts (overall survival (OS), 31.0 vs. 19.9 months (M), HR=1.99, 95% CI 1.32-2.93, p=0.001). OS was 24.8 and 24.0 M in the Pre- and Post-Cx (HR 1.07; 95% CI 0.87-1.32, p=0.502). In multivariate analysis, P1CY1, over 65 years old and clinical N3 lymph node metastasis were identified as the independent prognostic factor for OS (p&lt;0.05). Conclusions: Although Pre-Cx showed favorable survival in case of achieving P0 and CY0, Pre-Cx did not show a survival benefit for GC pts with CY1 and /or P1.

Comparison of S-1 and S-1 plus cisplatin as post-operative chemotherapy for gastric carcinoma with peritoneal lavage cytology positive or localized peritoneum metastasis: A multicenter retrospective study.

109 Background: Peritoneal lavage cytology of class V and localized peritoneum metastasis of gastric cancer (GC) are defined as CY1 and P1 in the 14th edition of the Japanese Classification of GC. Because patients (pts) with CY1 and/or P1 have poor prognosis after resecting all macroscopically visible disease by standard surgical resection, post-operative chemotherapy (post-Cx) is commonly performed in the clinical practice in Japan. However, no standard chemotherapy has not been established. The aim of this study was to investigate the efficacy of post-Cx in patients with CY1 and/or P1. Methods: We retrospectively reviewed the GC pts who were diagnosed to have CY1 and/or P1 at 34 institutions participating in the Stomach Cancer Group of Japan Clinical Oncology Group between 2007 and 2012. Inclusion criteria were: PS 0-2, histology of adenocarcinoma, no distant metastasis other than CY1 or P1, no prior treatment for GC. The subject of this study was the patients who received surgery followed by post-Cx. Results: A total of 824 pts were collected from 34 institutions. Of the 506 eligible pts, 444 pts underwent standard gastrectomy followed by post-Cx: S-1 (n=267), S1 plus cisplatin (SP) (n=114) or others (n=63). 62 pts did not receive post-Cx (non-Cx). Median age for the S1/SP/Others/non-Cx group were 69/63/66/75. In the S-1 group, pts with P0CY1/P1CY0/P1CY1 were 197/44/26, and those were 81/21/12 in SP, 45/9/9 in Others, and 44/7/11 in non-Cx. Conclusions: Post-Cx may have survival benefit after surgery for GC with CY1 or P1, while there seems no additional benefit over S-1. [Table: see text]

Overexpression of FGFR1 Promotes Peritoneal Dissemination Via Epithelial-to-Mesenchymal Transition in Gastric Cancer.

Peritoneal dissemination (PD) is one of the most common causes of cancer-related mortality in gastric cancer (GC). We aimed to identify PD-associated genes and investigate their role in GC. We identified FGFR1 as a putative PD-associated gene using a bioinformatics approach. The biological significance of FGFR1 in epithelial-to-mesenchymal transition (EMT) was evaluated according to the correlation with genes that participated in EMT and FGFR1 knockdown experiments. The associations between FGFR1 expression and the clinicopathological features were examined. FGFR1 expression positively correlated with SNAI1, VIM and ZEB1 expression, and negatively correlated with CDH1 expression. Knockdown of FGFR1 suppressed the malignant phenotype of GC cells. High FGFR1 expression significantly correlated with the peritoneal lavage cytology and synchronous PD positivity as well as poor prognosis. High FGFR1 expression was associated with PD via promotion of EMT and led to a poor prognosis of GC patients.

Prospective, single-center implementation and response evaluation of pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal metastasis.

Background:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a laparoscopy-guided administration of aerosolized chemotherapy. PIPAC seems to improve objective tumor response, survival and quality of life in patients with peritoneal metastasis. We assessed feasibility and efficacy of PIPAC in patients with peritoneal metastasis (PM).Methods:Patients were included in a prospective PIPAC protocol. Patients with colorectal PM were treated with oxaliplatin, patients with other primary tumors were treated with cisplatin and doxorubicin. Any chemotherapy exposure for healthcare workers was monitored by environmental and biological sampling. Feasibility was quantified by completion and complication rates. Response evaluation was documented by the peritoneal regression grading score (PRGS) and by peritoneal lavage cytology. Biopsy sites were marked by clips. Quality of life questionnaires were collected at baseline and after 60, 120 and 180 days.Results:A total of 35 patients with PM were treated with a median of three PIPAC procedures (range 1–9). Intraperitoneal access and completion of PIPAC was achieved in all patients. Few complications and adverse events were noted. There was no risk of chemotherapy exposure for healthcare workers. The mean PRGS was reduced significantly and a reduction of the PRGS was seen in 67% of the patients. Conversion from positive to negative cytology was achieved in 23% of the patients. Quality of life was stabilized from baseline to day 60.Conclusions:PIPAC is feasible and well tolerated, may stabilize the quality of life in patients with end-stage PM and may induce histological and cytological regression.This study is registered at www.clinicaltrials.gov [ClinicalTrials.gov identifier: NCT02320448].

Nuclear heat shock protein 110 expression is associated with poor prognosis and hyperthermo-chemotherapy resistance in gastric cancer patients with peritoneal metastasis.

AIMTo investigate the significance of heat shock protein 110 (HSP110) in gastric cancer (GC) patients with peritoneal metastasis undergoing hyperthermo-chemotherapy.METHODSPrimary GC patients (n = 14) with peritoneal metastasis or positive peritoneal lavage cytology who underwent distal or total gastrectomy between April 2000 and December 2011 were enrolled in this study. The patients underwent postoperative intraperitoneal hyperthermo-chemotherapy using a Thermotron RF-8 heating device two weeks after surgery. We analyzed nuclear HSP110 expression in surgically resected tumors using immunohistochemistry. Additionally, the effect of HSP110 suppression on hyptherthermo-chemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437.RESULTSHSP110 immnohistochemical staining in 14 GC patients showed that five (35.7%) samples belonged to the low expression group, and nine (64.3%) samples belonged to the high expression group. Progression-free survival was significantly shorter in the HSP110 high-expression group than in the low-expression group (P = 0.0313). However, no significant relationships were identified between HSP110 expression and the clinicopathological characteristics of patients. Furthermore, high HSP110 expression was not an independent prognostic factor in GC patients with peritoneal metastasis (P = 0.0625). HSP110 expression in MKN45 cells was suppressed by KNK437 at the hyperthermic temperature of 43 °C in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 °C, revealed that proliferation was significantly decreased when HSP110 was inhibited by KNK437. Additionally, HSP110 suppression via HSP inhibitor treatment increased cellular sensitivity to hyperthermo-chemotherapy in vitro.CONCLUSIONThe expression of nuclear HSP110 in GC patients might be a new marker of chemosensitivity and a therapeutic target for patients who are tolerant to existing hyperthermo-chemotherapies.

Is Pancreatic Head Cancer with Portal Venous Involvement Really Borderline Resectable? Appraisal of an Upfront Surgery Series.

It remains controversial whether the degree of venous involvement really is associated with borderline resectability of pancreatic cancer. A single-center retrospective review of patients who underwent upfront pancreaticoduodenectomy for T3 pancreatic cancer without arterial involvement was performed. The patients were classified as having resectable tumors without venous contact (R group), resectable tumors with venous contact of 180° or less (R-PV group), and borderline resectable tumors with venous contact greater than 180° (BR-PV group). The unresectable group included those who had unresected tumors with paraaortic lymph node metastasis, positive peritoneal lavage cytology, or locally advanced disease. The overall survival and prognostic factors were analyzed. The study enrolled 299 resected patients, including 141 patients in the R group, 119 patients in the R-PV group, and 39 patients in the BR-PV group. The overall survival did not differ significantly between the R-PV group and the BR-PV group (median survival, 20.7 vs 18.6months; P=0.807). Among the 158 patients who had tumors with venous contact, only a tumor size of 50mm or larger (P=0.041) was an independent prognostic factor in a multivariate analysis, and the overall survival for the patients with both venous contact and tumor size 50mm or larger was comparable with that for the unresectable group (P=0.547). The degree of venous involvement may not be associated with the resectability of pancreatic head cancer, whereas tumors 50mm in size or larger that develop venous invasion may be categorized as borderline resectable pancreatic cancers.

Abstract 724: Clinical impact of modified telomerase-specific adenovirus-based identification of viable-peritoneal tumor cells in peritoneal lavage fluid in patients with potentially resectable pancreatic cancer

Abstract Pancreatic cancer (PC) is a highly aggressive disease with dismal prognosis. Although only a surgical resection can offer the chance of a cure, the 5-year survival rate after a potentially curative resection have been reported to be a low as 10-30 %. In PC, the presence of peritoneal carcinomatosis preclude the possibility of surgical cure, irrespective of the resectability of the primary tumor. Peritoneal lavage cytology (CY) is used widely in the diagnosis and staging of gastric and pancreatic cancer. Positive CY findings (CY+) in PC is defined as stage IV disease, however, the true value of CY+ for the patient’s prognosis remains controversial. We rise the question of whether CY+ status has predictive value for survival and early intraperitoneal recurrence. The aim of this study was to evaluate use of a new genetically modified telomerase-specific replication-selective adenovirus, expressing GFP (TelomeScan F35) in rapid detection of viable peritoneal tumor cell (v-PTC) dissemination of PC. This human clinical trial sought to determine if the presence of virally-detected, rare v-PTC predict peritoneal recurrence and patient outcome. This study was approved by the Osaka Police Hospital IRB. Patients with resectable cytologically or histologically proven ductal adenocarcinoma of the pancreas were enrolled. Peritoneal lavage fluid was harvested just after a laparotomy in 27 patients with PC. Half of the fluid was examined by cytology with papanicolau staining and MOC-31 immunostaining and the remaining half was used to detect v-PTC with TelomeScan F35. To distinguish between leucocyte and cells with epithelial origin, cells were stained with anti-CD45 Ab. To further distinguish cells with primary tumor origin, cells were labeled with anti-CEA and anti-CA19-9 Abs. GFP-positive and CD45-negative, and either CEA- or CA19-9-positive cells were counted as v-PTC. Patients were followed after surgery to evaluate its clinical significance. Among 27 patients aged 57-91 years (16 males and 11 females), 3 were cytologically positive (CY+), other 3 were virally positive by TelomeScan F35 (v-PTC+). All 27 patients underwent a surgical resection (PD/DP/TP/H-PD=13/7/6/1). One patient was double positive (CY+/v-PTC+), and postoperative peritoneal recurrence early occurred at 5 month after resection despite adjvant chemotherapy. 2 were CY+, but v-PTC-, and no recurrence in the abdominal cavity were observed (0%). On the other hand, other 2 were CY-, but v-PTC+, and one of these 2 patients occurred local recurrence in the abdominal cavity (50%). Remaining 22 patients (CY-/v-PTC-) were observed with neither local recurrence nor distant metastasis. In conclusion, the TelomeScan F35-based v-PTC detection may be an independent prognostic factor in patients with resectable PC and had close association with local or peritoneal recurrence. Citation Format: Masahiro Tanemura, Kenta Furukawa, Soichiro Mori, Masahisa Otsuka, Youzo Suzuki, Mitsuyoshi Tei, Toru Masuzawa, Kentaro Kishi, Yasuo Urata, Hiroki Akamatsu. Clinical impact of modified telomerase-specific adenovirus-based identification of viable-peritoneal tumor cells in peritoneal lavage fluid in patients with potentially resectable pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 724. doi:10.1158/1538-7445.AM2017-724

FBXO50 Enhances the Malignant Behavior of Gastric Cancer Cells.

Challenges to our understanding the molecular mechanisms of the progression of gastric cancer (GC) must be overcome to facilitate the identification of novel biomarkers and therapeutic targets. In this article, we analyzed the expression of the gene encoding F-box-only 50 (FBXO50) and determined whether it contributes to the malignant phenotype of GC. FBXO50 messenger RNA (mRNA) levels and copy numbers of the FBXO50 locus were determined in 10 GC cell lines and a nontumorigenic epithelial cell line. Polymerase chain reaction array analysis was performed to identify genes coordinately expressed with FBXO50. The effects of inhibiting FBXO50 on GC cell proliferation, adhesion, invasiveness, and migration were evaluated using a small interfering RNA targeted to FBXO50 mRNA. To evaluate the clinical significance of FBXO50 expression, we determined the levels of FBXO50 mRNA in tissues acquired from 200 patients with GC. The levels of FBXO50 mRNA were increased in five GC cell lines and positively correlated with those of ITGA5, ITGB1, MMP2, MSN, COL5A2, GNG11, and WNT5A. Copy number gain of the FBXO50 locus was detected in four GC cell lines. Inhibition of FBXO50 expression significantly decreased the proliferation, adhesion, migration, and invasiveness of GC cell lines. In clinical samples, high FBXO50 expression correlated with increased pT4, invasive growth, lymph node metastasis, and positive peritoneal lavage cytology. Patients with high FBXO50 expression had a significantly higher prevalence of recurrence after curative gastrectomy and were more likely to experience shorter overall survival. FBXO50 may represent a biomarker for GC phenotypes and as a target for therapy.

Intraoperative peritoneal lavage cytology offers prognostic significance for gastric cancer patients with curative resection.

Outcomes of patients with gastric cancer who exhibit positive peritoneal lavage cytology findings (CY +) vary by diagnostic methods because of quantitative and qualitative cancer cell diversity. This study sought to establish practical diagnostic criteria for performing curative resections, based on peritoneal lavage cytology findings in gastric cancer patients. We enrolled 1028 patients with gastric cancer who underwent R0/1 (n = 911) or R2 (n = 117) resections and analyzed relationships between cancer cell findings in peritoneal lavage fluid and clinicopathological factors in the R0/1 group. We found 68 patients with CY + status. Receiver operating characteristic analyses and multivariate analyses showed that the presence of ≥1 signet ring cell, ≥5 cell clusters or ≥50 isolated cancer cells in peritoneal lavage fluid predicted poor prognoses in the 68 CY + patients. High‐risk CY + group patients with at least one of the above predictors had the highest hazard ratio (HR = 3.28, P < 0.001). The remaining (low‐risk) patients had a survival curve similar to that of patients with a normal cytology. The high‐risk CY + patients who underwent R1 resection had poor prognoses despite no macroscopic peritoneal metastasis (2% 5‐year survival)—equivalent to that of patients who underwent R2 resection. The CY + criteria defined in this study could help identify candidates for curative resection as an initial therapy for gastric cancer.

Staging laparoscopy for advanced gastric cancer: significance of preoperative clinicopathological factors.

Although the use of staging laparoscopy (SL) for detecting peritoneal metastasis (P) and determining peritoneal lavage cytology (CY) is widespread in advanced gastric cancer, an indication for SL based on preoperative clinicopathological factors is controversial. From May 2006 to September 2015, 120 patients with advanced gastric cancer with primary tumors ≥5cm and/or with bulky regional lymph nodes (bulky N) underwent SL for assessment of P/CY status. Clinicopathological factors were analyzed retrospectively to determine their influence on peritoneal spread (P1 and/or CY1). An additional analysis of 379 consecutive patients with clinically T2 or deeper gastric cancer in the same time period was carried out to confirm the SL results. Peritoneal spread was confirmed by SL in 54 cases (45%). The presence of type-4 tumors (n=38, p<0.0001) and diffuse-type tumors (n=85, p=0.04) correlated significantly with peritoneal spread. These two factors were also correlated significantly with increased peritoneal spread in a subgroup analysis among patients with tumors with bulky N (n=44). The additional analysis of 379 patients showed results consistent with the SL results. The frequency of peritoneal spread was 78% among type-4 tumors, 47% among diffuse-type tumors ≥5cm, and 38% among diffuse-type tumors with bulky N, whereas among intestinal-type tumors, it was 18% in tumors ≥5cm and 13% among tumors with bulky N. Among tumors ≥5cm or with bulky N, type-4 tumors and diffuse-type tumors had a high potential for peritoneal spread and patients with such tumors were considered more suitable candidates for SL.

Risk factors for latent distant organ metastasis detected by staging laparoscopy in patients with radiologically defined locally advanced pancreatic ductal adenocarcinoma.

We aimed to identify risk factors for latent distant organ metastasis in patients with radiographically defined locally advanced (RDLA) pancreatic ductal adenocarcinoma (PDAC). RDLA disease was defined as unresectable disease without distant organ metastasis based on resectability status by NCCN guidelines. Between January 2005 and November 2015, 110 consecutive patients underwent staging laparoscopy to rule out latent distant metastasis. Univariate and multivariate analyses were performed to identify risk factors for latent distant organ metastasis or peritoneal metastasis (PM), defined as peritoneal dissemination and/or positive peritoneal lavage cytology (PPC). Latent distant organ metastasis was diagnosed by staging laparoscopy in 62 patients. PPC was found in 23%, peritoneal dissemination in 19%, and liver metastasis in 15%. Univariate analysis showed tumor location, preoperative CA 19-9 level and tumor size, and multivariate analysis revealed tumor size >55mm and CA 19-9 level>60IU/ml as risk factors for latent distant metastasis. Multivariate analysis showed pancreas body-tail tumors and tumor size >42mm as risk factors for PM; 65.4% of pancreas body-tail tumors >42mm had PM. Patients with large pancreas body-tail tumors and high CA 19-9 level are at greater risk for latent distant organ metastasis or PM, and should undergo staging laparoscopy routinely for accurate diagnosis (UMIN000023125).

Conversion therapy for pancreatic cancer with peritoneal metastases using intravenous and intraperitoneal paclitaxel with S-1.

Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body. The patient underwent abdominal surgery, but no excision was performed, as two peritoneal metastases in the bursa omentalis were detected. Combination therapy was initiated, consisting of intravenous and intraperitoneal paclitaxel with S-1 as a single-center clinical trial. The regimen consisted with 2-week administration of S-1 (80 mg per day) followed by 1 week of rest, intravenous paclitaxel 50 mg/m2, and intraperitoneal paclitaxel 20 mg/m2 by a peritoneal access device on days 1 and 8. Over the seven cycles of the chemotherapy, the primary lesion did not change in size, and peritoneal lavage cytology remained negative. After confirming the disappearance of the peritoneal lesions by exploratory laparoscopy, the patient underwent distal pancreatectomy combined with resection of the transverse mesocolon and stomach wall. Thus, the 2-way chemotherapy of intravenous and intraperitoneal paclitaxel with S-1 was well-tolerated and was able to convert pancreatic cancer with peritoneal metastases to resectable disease.