scholarly journals Detection of free cancer cells in peritoneal cavity in patients surgically treated for gastric adenocarcinoma

2006 ◽  
Vol 63 (4) ◽  
pp. 349-356 ◽  
Author(s):  
Zoran Kostic ◽  
Vladimir Cuk ◽  
Radojka Bokun ◽  
Dragan Ignjatovic ◽  
Slavica Usaj-Knezevic ◽  
...  

Bacground/Aim. Peritoneal metastasis is a leading cause of therapeutic failure after an operative treatment of patients with gastric adenocarcinoma. Free cancer cells might induce or indicate an early peritoneal seeding with a subsequent peritoneal metastasis. The aim of this study was to determine the frequency of the presence of free cancer cells in the peritoneal cavity in the patients surgically treated for gastric adenocarcinoma, and its relation to certain clinical, operative and pathohistological parameters. Methods. Inside a period from April 2000, and April 2004, the total of 100 patients underwent intraoperative peritoneal lavage for cytological examination. Immediately after the laparotomy, 200 ml physiologic saline, heated to 37 ?C, was introduced into the abdominal cavity, manually dispersed and collected from the region around the gastric tumor and the pouch of Douglas. The nucleated cell layer was smeared on four glass slides for every patient and dyed with May-Gr?nwald-Giemsa stain. The cytological findings were defined as positive or negative according to the presence of cancer cells. The frequency of positive cytological findings was compared to the location and the diameter of the cancer, pathohistological type of carcinoma, pathohistological stage of the disease, lymph node and the liver and/or peritoneal metastases and the type of surgical procedure. Results. Free cancer cells were found in 24 (24%) of the patients, while in 76 (76%) of them cytological findings were negative. A statistically highly significant difference (p ? 0.001) in the frequency of positive cytological finding was found between the groups of patients with and without cancer invasion of serosa, with cancer diameters > 5 cm and ? 5 cm, in the stage of disease I, II and III, IV, with macroscopically present and without metastases, with resection and D2 lymphadenectomy and palliative procedure. Free cancer cells were statistically more frequently (p ? 0.05) detected in the patients with lymph nodes metastases comparing to the patients without lymph nodes involvement. The results of the univariate analysis showed that the cancer diameter > 5 cm, tumor invasion of serosa, pathohistological stage of the disease III and IV and macroscopically visible metastases were the most important risk factors for the free cancer cells detection. Conclusion. Peritoneal lavage cytology was shown to be a useful tool for the detection of the group of patients with greatest risk of peritoneal dissemination. The frequency of positive cytological findings was highly associated with the diameter of the tumor and the cancer invasion of serosa. Cytological examination of peritoneal lavage fluid improved the accuracy of staging and selection of patients who might have benefit from neoadjuvant chemotherapy.

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Masafumi Kuramoto ◽  
Shinya Shimada ◽  
Satoshi Ikeshima ◽  
Akinobu Matsuo ◽  
Hiroshi Kuhara ◽  
...  

Peritoneal metastasis, which often arises in patients with advanced gastric cancer, is well known as a miserable and ill-fated disease. Once peritoneal metastasis is formed, it is extremely difficult to defeat. We advocated EIPL (extensive intraoperative peritoneal lavage) as a useful and practical adjuvant surgical technique for those gastric cancer patients who are likely to suffer from peritoneal recurrence. In this paper, we review the effect of EIPL therapy on prevention of peritoneal recurrence on patients with peritoneal free cancer cells without overt peritoneal metastasis (CY+/P−) through the prospective randomized study, and we verified its potential as an optimal and standard prophylactic therapeutic strategy for peritoneal recurrence.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 63-63
Author(s):  
S. Emoto ◽  
J. Kitayama ◽  
H. Ishigami ◽  
H. Yamaguchi ◽  
H. Yamashita ◽  
...  

63 Background: Peritoneal metastasis is considered to develop from carcinoma cells detached from the serosal surface of the primary site and dispersed in the peritoneal cavity. And oxygen is one of the most important environmental factors for tumor development. To investigate the oxygenation condition in the abdominal cavity, that is largely unknown, we collected ascitic fluid from patients with peritoneal dissemination of gastric cancer and measured pO2 of it. Methods: In 19 patients with peritoneal dissemination of gastric cancer, who had a considerable amount of ascites and was receiving systemic and/or intraperitoneal chemotherapy, ascitic fluid was collected at the bedside in room air, and its pH, pCO2 and pO2 were measured using a blood gas analyzer immediately. Results: In 19 patients, pH of malignant ascites was significantly lower than that of arterial blood (7.39 ± 0.069 vs 7.44 ± 0.025 mmHg, p < 0.05). pCO2 tended to be higher in ascites than in arterial blood. Unexpectedly, pO2 in malignant ascites showed relatively high values (85.47 ± 23.31 mmHg), which were mostly the same as that of arterial blood (97.19 ± 10.40 mmHg, p = 0.149), and appeared to be higher than that in solid tumor tissue. Conclusions: Malignant ascites in gastric cancer patients showed an unexpectedly high oxygen tension, which was almost the same as that of arterial blood. The hyperpermeability condition may enable efficient oxygen delivery to peritoneal fluid via the microvessels lining the peritoneal cavity. Since the oxygen level critically affects the sensitivity of tumor cells to chemotherapeutic agents through metabolic transformation, aerobic conditions may be beneficial for the progression of peritoneal metastasis and also clinically important in considering the efficacy of chemotherapy. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4092-4092
Author(s):  
Satoshi Murata ◽  
Katsushi Takebayashi ◽  
Masatsugu Kojima ◽  
Hiroshi Yamamoto ◽  
Tsuyoshi Yamaguchi ◽  
...  

4092 Background: A large number of advanced gastric cancer patients undergoing curative gastrectomy with D2 lymph node dissection (D2 gastrectomy) show peritoneal metastasis. The source of these metastatic cells and their treatment remain unclear. We examined the mechanism of surgery-induced peritoneal metastasis and determined the appropriate intraoperative treatment. Methods: (1) Curative gastrectomy was performed for 102 gastric cancer patients. Peritoneal lavage fluid was collected before and after gastrectomy. Cytology, RT-PCR, and cell culture were used to determine the presence of cancer cells. Proliferative potential of tumor cells was evaluated using Ki-67 staining. Tumorigenic capacity was assessed by cell injection into the peritoneal cavity of NOD/ShiJic-scid mice. (2) Fifty clinical T3(SE) or T4(SI) advanced gastric cancer patients undergoing curative D2 gastrectomy prospectively received intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) in a phase II trial. HIPEC comprised 50 mg CDDP, 10 mg MMC, and 1000 mg 5-FU in 5 L saline maintained at 42–43C° for 30 min. Results: (1) Of 102 peritoneal lavage fluid samples obtained before gastrectomy, 57 from both early and advanced cancer patients did not contain CEA or CK20 mRNA amplification products or cancer cells. Of these 57 samples, CEA or CK20 mRNA was detected in 35 and viable cancer cells were identified in 24 after gastrectomy. Viable cancer cells in all 24 cases showed Ki-67 positivity, indicating proliferative activity. Cultured viable cancer cells developed into peritoneal tumor nodules after spill over into the peritoneal cavity in NOD/ShiJic-scid mice. (2) Fifty patients were eligible for the phase II clinical trial. The overall 5-year survival rate for all patients was 92.4%. This rate in patients with pT2(ss) (n = 12), pT3(se) (n = 35), and pT4(si) (n = 3) disease was 90.0%, 92.3%, and 100%, respectively. Only 2 patients (4%) showed peritoneal relapse. Conclusions: Viable tumorigenic cancer cells spilled over the peritoneal cavity during curative gastrectomy. Intraoperative HIPEC following curative D2 gastrectomy effectively prevented peritoneal metastasis, thereby potentially improving the prognosis of patients with advanced gastric cancer.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 96-96 ◽  
Author(s):  
Masaki Aizawa ◽  
Hironori Ishigami ◽  
Hiroshi Yabusaki ◽  
Atsushi Nashimoto ◽  
Haruhiko Imamoto ◽  
...  

96 Background: The presence of free cancer cells in the peritoneal cavity has been known as a poor prognostic factor in gastric cancer patients. Intraperitoneal (IP) paclitaxel (PTX) provides powerful local effects in the peritoneal cavity, and we previously reported the efficacy and safety of a regimen combining IP PTX with S-1/PTX in gastric cancer patients with peritoneal metastasis. This multicenter phase II study was conducted to evaluate the efficacy of IP PTX plus S-1/PTX for gastric cancer with positive peritoneal cytology. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, intraperitoneal free cancer cells confirmed by peritoneal washing cytology, and no evidence of overt distant metastasis including macroscopic peritoneal metastasis. Patients were administered IP PTX 20 mg/m2, intravenous PTX 50 mg/m2 on days 1 and 8, and S-1 80 mg/m2/day on days 1-14, q3 weeks. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Thirty eight patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 12.5 (range 2-35). The 1-year OS rate was 84.2% (95 % confidence interval, 68.2-92.6%). Of 3 patients with target lesions, partial response and stable disease were obtained in 2 and 1 patient(s), respectively. The peritoneal cytology findings converted from positive to negative in 36 (94.7 %) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 45 % and 26 %, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), leukopenia (7%) and anemia (8%). Regarding adverse events related to IP port, 2 patients developed swelling around the port site. Conclusions: IP PTX with S-1/PTX was suggested to be a promising option for gastric cancer with positive peritoneal cytology through the clearance of cancer cells in the peritoneal cavity. Clinical trial information: UMIN000002850.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15516-e15516 ◽  
Author(s):  
Changsong QI ◽  
Pansong Li ◽  
Yanting Hu ◽  
Lianpeng Chang ◽  
Yi Wu ◽  
...  

e15516 Background: Peritoneal metastasis (PM) is the most frequent mode of distant metastasis in advanced gastric cancer (GC). Most PM could cause peritoneal effusion. However, the cytological examination of cancer cells in peritoneal effusion is less sensitive to the identification of PM early; the specificity of serum biomarkers in peritoneal effusion is poor. It is necessary to assess the feasibility of peritoneal effusion circulating tumor DNA (ctDNA) for the PM diagnosis. Methods: 22 GCs with clinically confirmed PM as positive subjects and 11 non-cancers without PM as negative control were recruited. GC tissues were collected from 16 positive subjects. Peritoneal effusion supernatant (AS), peritoneal effusion cells (AC), and plasma were collected from each subject. Next generation sequencing (NGS) was performed using a 1021-gene panel. Sensitivity and specificity for the diagnosis of GC with PM were assessed. Results: Median age of 22 GCs with PM was 57 yrs. 12 patients were male. Diffused and mixed-type accounted for 73%. For 45% of patients, primary tumor was found in gastric body. In tissue samples, recurrent genes were TP53 (63%), CDH1 (50%), RHOA (19%), TGFBR1 (19%), KRAS (13%), and PIK3CA (13%). Private and tumor-derived mutations were found in the AS, AC, and plasma. 95% of (21/22), 82% (18/22), and 77% (17/22) of AS, AC, and plasma samples carried mutations, respectively. AS had more mutations than AC and plasma (Wilcoxon’s matched-pairs signed-ranked test, AS vs AC, p= 0.006; AS vs plasma, p = 0.013). 98% of the AC and 80% plasma mutations were contained in AS, Variant allele frequency (VAF) in AS was higher than others (Mann Whitney test, AS vs AC, p= 0.038; AS vs plasma, p< 0.001). In 22 GCs with PM, 3 were identified with no cancer cells in AS using cytological examination. Of these, 3 were detected with mutations in AS, one with mutations in AC. Mutations were detected in only one negative control AS and AC. Receiver operating characteristic (ROC) curve showed the number of mutations was related to PM (AS: AUC 0.93, 95% CI 0.82-1.00, p< 0.001; AC: AUC 0.85, 95% CI 0.70-1.00, p= 0.001). When the threshold was determined with one mutation, the sensitivity and specificity were 95% and 91% in AS, 82% and 91% in AC, respectively. Conclusions: Peritoneal effusion ctDNA contained tumor-derived and specific mutations. Peritoneal effusion ctDNA can be used for the auxiliary diagnosis of PM.


2019 ◽  
Vol 20 (21) ◽  
pp. 5444 ◽  
Author(s):  
Archid ◽  
Solass ◽  
Tempfer ◽  
Königsrainer ◽  
Adolph ◽  
...  

: Patients with peritoneal metastasis (PM) of gastrointestinal and gynecological origin present with a nutritional deficit characterized by increased resting energy expenditure (REE), loss of muscle mass, and protein catabolism. Progression of peritoneal metastasis, as with other advanced malignancies, is associated with cancer cachexia anorexia syndrome (CAS), involving poor appetite (anorexia), involuntary weight loss, and chronic inflammation. Eventual causes of mortality include dysfunctional metabolism and energy store exhaustion. Etiology of CAS in PM patients is multifactorial including tumor growth, host response, cytokine release, systemic inflammation, proteolysis, lipolysis, malignant small bowel obstruction, ascites, and gastrointestinal side effects of drug therapy (chemotherapy, opioids). Metabolic changes of CAS in PM relate more to a systemic inflammatory response than an adaptation to starvation. Metabolic reprogramming is required for cancer cells shed into the peritoneal cavity to resist anoikis (i.e., programmed cell death). Profound changes in hexokinase metabolism are needed to compensate ineffective oxidative phosphorylation in mitochondria. During the development of PM, hypoxia inducible factor-1α (HIF-1α) plays a key role in activating both aerobic and anaerobic glycolysis, increasing the uptake of glucose, lipid, and glutamine into cancer cells. HIF-1α upregulates hexokinase II, phosphoglycerate kinase 1 (PGK1), pyruvate dehydrogenase kinase (PDK), pyruvate kinase muscle isoenzyme 2 (PKM2), lactate dehydrogenase (LDH) and glucose transporters (GLUT) and promotes cytoplasmic glycolysis. HIF-1α also stimulates the utilization of glutamine and fatty acids as alternative energy substrates. Cancer cells in the peritoneal cavity interact with cancer-associated fibroblasts and adipocytes to meet metabolic demands and incorporate autophagy products for growth. Therapy of CAS in PM is challenging. Optimal nutritional intake alone including total parenteral nutrition is unable to reverse CAS. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) stabilized nutritional status in a significant proportion of PM patients. Agents targeting the mechanisms of CAS are under development.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16533-e16533
Author(s):  
Wei Wang ◽  
Wenjun Xiong ◽  
Yaohui Peng ◽  
Jin Li ◽  
Haipeng Huang ◽  
...  

e16533 Background: Gastric cancer (GC) with peritoneal metastasis (PM) is associated with a poor prognosis. The free cancer cells are the prerequisite of peritoneal metastasis. Peritoneal lavage cytology (PLC) is the main measure to identify the free cancer cells, but its positive rate is relatively low. This study aims to investigate the association between the result PLC and peritoneal metastasis for GC. Methods: From November 2017 to December 2019, 33 patients with GC were confirmed with PM through computerized tomography or diagnostic laparoscopy. The inflow and outflow catheters were inserted laparoscopically in all patients for postoperative hyperthermic intraperitoneal chemotherapy. PLC was performed with at least 200 ml of fluid and examined by measures of cytology and immunocytopathology. Ascites was aspirated if detected or 500 milliliter of normal saline infused the Douglas cavity, para-colic gutters and the right and left sub-phrenic cavity and then aspirated. Results: There were 15 males and 18 females and the median age was 56 (24-84) years old. All patients had a cT4a/cT4b and an N-positive tumor. The overall positive PLC (PLC+) rate was 63.6% (21/33). The distribution of Lauren classification was respectively 5 (15.2%) intestinal, 26 (78.8%) diffused and 2 (6.1%) mixed tumor. The diffused cases had a higher rate of PLC+ ( P = 0.004). All 5 intestinal GC had a negative PLC (PLC-). 71.4% (20/28) of patients with a grade G3/G4 had a PLC+, compared, no PLC+ was recorded in 5 grade G1/G2 patients (P = 0.003). The median peritoneal carcinomatosis index (PCI) was 14 (1-39). The PLC+ rate was 94.7% (18/19) in PCI > = 10 group and 21.4% (3/14) in PCI < 10 group ( P < 0.001). The median ascites was 200 (0-7000) ml. The PLC+ rate was 88.2% 15/17) in ascites > = 200 ml group and 37.5% (6/16) in ascites < 10 ml ( P = 0.002). The median follow-up was 13(1-27) months and the overall survival was 75.8%, but no significance was detected between PLC+ group and PLC- group. Conclusions: The present study suggested that the result of PLC was not completely coincided with PM for GC by measures of cytology and immunocytopathology, especially for intestinal and grade G1/G2 tumor.


Medicina ◽  
2019 ◽  
Vol 55 (7) ◽  
pp. 388 ◽  
Author(s):  
Farhad Barzegar ◽  
Mohammad Zaefizadeh ◽  
Reza Yari ◽  
Ali Salehzadeh

Background and objectives: Human gastric adenocarcinoma (AGS) is one of the most common malignant cancers worldwide. The present study aimed to transfer oleuropein into cancer cells using synthetic paramagnetic nanoparticles and study their effect on the AGS (ATCC® CRL1739™) cell line. Materials and Methods: Paramagnetic nano-oleuropein was synthesized using four-stage co-precipitation by developing NH-connected bridges and was evaluated by EDS, SEM and FTIR methods. Different concentrations of magnetic oleuropein (0, 0.15, 0.45, 1.37, 4.12, 12.35, 37.04, 111.11, 333.33, 1000 µg/mL) were used to treat the AGS cell line in a completely randomized design using a statistical framework with three replicates. The relative expression rate of miR-200 and KRAS oncogenes was evaluated using real-time PCR. The inhibition rate of the AGS cells was assessed using the MTT test at 24, 48 and 72 h intervals. Results: The results showed that there was a significant difference between the inhibition rates of magnetic nano-oleuropein at IC50-24h (23.6 µg/mL), IC50-48h (15.2 µg/mL) and IC50-72h (9.2 µg/mL). Real-time PCR indicated that the relative expression of KRAS and miR-200 genes was highest at IC50 at these intervals. Conclusions: Magnetic nano-oleuropein can be subjected to objective testing and clinical evaluations as a natural antioxidant to prevent and treat gastric adenocarcinoma.


2012 ◽  
Vol 27 (7) ◽  
pp. 494-498 ◽  
Author(s):  
Marcos Célio Brocco ◽  
Danilo Nagib Salomão Paulo ◽  
Carlos Eduardo David de Almeida ◽  
Antonio Roberto Carraretto ◽  
Sigmar Aurea Cabral ◽  
...  

PURPOSE: The objective of this study was to assess the cytokine serum levels of IL-6 and TNF-α in rats subjected to fecal peritonitis and treated with peritoneal lavage with 0.2% ropivacaine by peritoneal lavage. METHODS: We subjected 16 Wistar rats to laparotomy 6 hours after the induction of fecal peritonitis with autogenous stool and subsequently divided the rats randomly into 4 groups: I-control, no treatment; II- drying of the abdominal cavity; III- lavage of the abdominal cavity with 3 mL of 0.9% normal saline and drying; IV- lavage of the abdominal cavity with 3 mL of 0.2% ropivacaine and drying. Six hours following the laparotomy, the animals underwent cardiac puncture, and 1 mL of blood was collected for cytokine assessment before the animals were euthanized. RESULTS: The lavage with ropivacaine resulted in smaller TNF-α levels compared with those observed in the other treatment groups (p <0.05). Regarding IL-6, the ropivacaine group showed lower cytokine levels than those observed in groups I and II, but there was no significant difference (p> 0.05) between groups III and IV. CONCLUSION: Peritoneal lavage with 0.2% ropivacaine was shown to reduce plasma levels of IL-6 and TNF-α in the treatment of fecal peritonitis in rats.


PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e99650 ◽  
Author(s):  
Xiao-Long Chen ◽  
Kun Yang ◽  
Wei-Han Zhang ◽  
Xin-Zu Chen ◽  
Bo Zhang ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document