Intraperitoneal Free Cancer Cells Research Articles

Long noncoding RNA small nucleolar RNA host gene 1 as a potential novel biomarker for intraperitoneal free cancer cells in colorectal cancer

Colorectal cancer (CRC) is a prevalent cancer with intraperitoneal free cancer cells (IFCCs) playing a significant role in prognosis, especially during surgeries. The identification of IFCCs is crucial for determining the stage and treatment of patients with CRC. Existing methods for IFCC detection, such as conventional cytology, immunocytochemistry (ICC), and polymerase chain reaction (PCR), have limitations in sensitivity and specificity. This study investigates the potential of long noncoding RNA (lncRNA) SNHG1 as a biomarker for detecting IFCCs in patients with CRC. Testing on a cohort of 91 patients with CRC and 26 patients with gastrointestinal benign disease showed that SNHG1 outperformed CEA in distinguishing CRC cells and detecting IFCCs across different disease stages. SNHG1 demonstrated higher sensitivity (76.1% vs. 43.1%) and specificity (68.4% vs. 52.3%) than CEA for IFCC detection in patients with CRC, suggesting its promising role as a clinical method for identifying IFCCs in CRC.

Staging laparoscopy with peritoneal lavage to identify peritoneal metastases and free intraperitoneal cancer cells in the management of locally advanced gastric cancer

IntroductionGastric cancer often presents in advanced stage with a significant risk for peritoneal dissemination. Staging laparoscopy can be used to detect peritoneal carcinomatosis (PC+) and free cancer cells in peritoneal lavage cytology (CY+). The current study aimed to present the outcomes of staging laparoscopy and the prognosis of PC+ and CY+ in a Swedish high-volume center. Materials and methodsA cohort study including all consecutive patients with locally advanced gastric cancer who underwent staging laparoscopy between February 2008 and October 2022. The laparoscopy findings were categorized as PC+, PC-CY+ (positive cytology without peritoneal carcinomatosis) or negative laparoscopy (PC-CY-). The primary endpoint was overall survival (OS) stratified by laparoscopy findings. The secondary endpoint was OS within each laparoscopy finding group stratified by subsequent treatment. ResultsAmong 168 patients who underwent staging laparoscopy, 78 patients (46%) had PC-CY-, 29 patients (17%) had PC-CY+ and 61 patients (36%) had PC+. Decreased OS was observed for both PC-CY+ patients (aHR 2.14, 95% CI 1.13–4.06) and PC+ patients (aHR 5.36, 95% CI 3.21–8.93), compared to PC-CY-. Patients with PC-CY+ who converted to PC-CY- after chemotherapy and underwent tumor resection seemed to have a better prognosis compared to patients with persisting PC-CY+. ConclusionsStaging laparoscopy is an important tool in the staging of locally advanced gastric cancer. Tumor resection for patients with PC-CY+ who convert to PC-CY- may lead to improved survival for these patients.

Phase II clinical study evaluating the efficacy and safety of disitamab vedotin combined with sintilimab and S-1 in the conversion treatment of HER2-overexpression unresectable gastric cancer.

TPS428 Background: Gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA) is the fifth commonest cancer and the fourth leading cause of cancer deaths worldwide. In about 30% to 40% of patients with advanced gastric cancer have lost the opportunity for radical surgery at the first diagnosis, and the overall 5-year survival rate is less than 50%. In recent years, conversion therapy has shown great promise. Disitamab vedotin is an antibody-drug conjugate comprising a novel HER2-directed monoclonal antibody, In previous study C008, RC48 showed a good safety profile and promising activity towards GC, and showed equivalent efficacy for HER2 IHC 2+ or HER2 IHC 3+ tumors. Methods: This study is a single-arm, phase II trial carry out at 16 academic hospitals in China, and will evaluate DV combined with Sintilimab and S-1 in patients with HER2-expressing unresectable gastric cancer. Eligible patients are at ≥ 18 to ≤ 75 years old; histologically confirmed, unresectable stage IV GC or GEJA; Single initial unresectable factor. For example, peritoneal metastasis (P1), Intraperitoneal free cancer cells positive (CY1), Paraaortic lymph node metastasis, liver metastasis (≤ 3 lesions, and ≤ 5 cm for a single lesion), ovarian metastasis; and documented histologically confirmed HER2 IHC 3+ or 2+; ECOG 0-1; at least one unresectable, measurable tumor lesion according to the RECIST version 1.1; adaptable function of the heart, liver, and kidney. 30 patients will be enrolled in this trial and receive Disitamab Vedotin(2.5mg/kg, IV, Q3W), Sintilimab (200 mg, IV, Q3W) and S-1 (twice daily on D1-14 are given at a dose calculate according to the body surface area and repeated every 3 weeks), until patients assessed by MDT to meet the criteria for surgical resection undergo gastrectomy. And the patients with peritoneal dissemination will combine with intraperitoneal administration of paclitaxel (60mg / m2, Q3W). The primary endpoint is R0 resection rate, Secondary endpoints include cORR, OS, RFS and safety. Seven patients have been enrolled in this study. Clinical trial information: NCT05627414 .

Development of membrane anatomy theory in gastric cancer surgery

In the past decade, the concept of membrane anatomy has been gradually applied in gastric cancer surgery. Based on this theory, D2 lymphadenectomy plus complete mesogastric excision (D2+CME) has been proposed, which has been demonstrated to significantly reduce intraoperative bleeding and intraperitoneal free cancer cells during surgery, decrease surgical complications, and improve survival. These results indicate that membrane anatomy is feasible and efficacious in gastric cancer surgery. In this review, we will describe the important contents of membrane anatomy, including "Metastasis V"(2013, 2015), proximal segmentation of dorsal mesogastrium (2015), D2+CME procedure (2016), "cancer leak"(2018), and surgical outcomes of D2+CME (2022).

Application and prospect of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastasis from colorectal cancer

Colorectal cancer is one of the common malignant tumors in China, and its incidence is increasing with years. As the second most common metastatic site of colorectal cancer, peritoneum is difficult to diagnose early and with a poor prognosis. Systemic intravenous chemotherapy was used as the main treatment strategy for peritoneal metastasis in the past, but its systemic toxic and side effects were obvious, and it could not effectively control tumor progression. In recent years, the continuous development of surgical techniques, concepts, and equipment, as well as the introduction of new chemotherapy drugs and targeted drugs have significantly improved the quality of life and prognosis of patients with peritoneal metastasis of colorectal cancer. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively eradicated the intraperitoneal free cancer cells and subclinical lesions, while reducing systemic side effects of chemotherapy drugs, and achieve the radical cure of the tumor at the macro and micro levels to the greatest extent. It has been used as the first-line treatment program for peritoneal metastasis of colorectal cancer at home and abroad. This article focuses on the analysis and summary of the survival efficacy, prognostic factor analysis, and chemotherapy safety of CRS+ HIPEC in the treatment of colorectal cancer peritoneal metastasis. The existing problems and controversies of HIPEC therapy are discussed simultaneously.

PCR-based quantitative detection of intraperitoneal free cancer cells for predicting locoregional recurrence after rectal cancer resection.

Locoregional recurrence after curative resection remains an important issue in the treatment of colorectal cancer (CRC). The aim of the present study was to investigate the clinical significance of quantitative detection of intraperitoneal free cancer cells by a PCR-based method for predicting locoregional recurrence after CRC resection. A total of 114 patients with CRC were enrolled between March 2017 and December 2018, and 95 patients with Stage I-III CRC were analyzed. Peritoneal lavage fluid was collected before and after tumour resection and subjected to cytology and quantitative reverse transcription-PCR (qRT-PCR) with carcinoembryonic antigen (CEA) as a genetic marker. 2.1% of patients had positive cytology after resection, whereas 9.5% had positive CEA qRT-PCR (PCR+) after resection. Eight of nine PCR+ patients after resection had tumours in the rectum. Fifteen (15.8%) patients developed recurrence during the follow-up period, including three with locoregional recurrence. One of 86 (1.2%) PCR- patients and 2 of 9 (22.2%) PCR+ patients after resection developed locoregional recurrence. Overall and in rectal cancer patients, the 3-year cumulative risk of locoregional recurrence was 25.0% and 28.6% for PCR+ patients, which is significantly higher than PCR- patients (1.3% and 0%, P< 0.001 and P= 0.001, respectively). Intraperitoneal free cancer cells can serve as a sensitive predictor of locoregional recurrence after rectal cancer resection. qRT-PCR for CEA can be a suitable method for detecting intraperitoneal free cancer cells in peritoneal lavage fluid.

Surgical and systemic therapies for addressing occult disease in advanced epithelial ovarian cancer

The incidence of peritoneal recurrence in advanced epithelial ovarian cancer (EOC) is high and could be attributed to the high prevalence of occult disease the persists despite complete cytoreductive surgery (CRS) and systemic chemotherapy. Several therapeutic approaches have been used to address such occult disease. Hyperthermic intraperitoneal chemotherapy (HIPEC) acts on microscopic disease as well as free intraperitoneal cancer cells shed during surgery, thus, reducing the risk of recurrence. Maintenance therapies like Poly ADP-Ribosyl Polymerase (PARP) inhibitors and the anti-angiogenic agent bevacizumab are used as maintenance therapies to delay recurrence. The most definitive way to eradicate such occult disease completely is resection of the peritoneum. The high preponderance of occult disease in the parietal peritoneum and some regions of the visceral peritoneum has led some surgeons to investigate the role of a total parietal peritonectomy (TPP) performed along with wide resection of the visceral peritoneum as a strategy for addressing occult disease. The mechanism of action differs from that of HIPEC and systemic therapies. It is possible that the benefit of each of these therapies is additive. EOC is a heterogeneous disease with a number of clinicopathological and molecular factors influencing the prognosis. There are likely to be different subgroups of patients that benefit from each of these 4 therapies or a combination of these. In this manuscript, we review the rationale and current evidence for the use of each of these therapies and discuss the potential role of a TPP in light of other therapies.

Progress in gastric cancer with positive peritoneal cytology

Gastric cancer with positive peritoneal cytology is a hotspot in the study of gastric cancer, and its prognosis is poor. Intraperitoneal free cancer cells may be associated with cancer cells migration, invasion and metastasis. Tumor T stage, peritoneal metastasis, lymph node metastasis, low histological differentiation, linitis plastica, adenocarcinoma of esophagogastric junction, and operation are the clinicopathological risk factors of gastric cancer with positive peritoneal cytology. Currently, the acquisition of free cancer cells is mainly through diagnostic laparoscopy combined with peritoneal lavage, and cytopathological examination is gold standard for diagnosis. Its treatment strategies are not in consensus, including preoperative chemotherapy combined with radical resection, postoperative chemotherapy and peritoneal local treatment, which can prolong the survival of patients. At present, postoperative chemotherapy is often used in China, and the best treatment strategies remain to be further studied.

Intra-operative hyperthermic intraperitoneal chemotherapy for prevention and treatment of peritoneal metastases from gastric cancer: a narrative review.

Peritoneal metastasis (PM) from gastric cancer (GC) has long been regarded as the terminal disease, lacking of effective treatments. In recent 40 years, cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), and early post-operative intraperitoneal chemotherapy (EPIC), has been recommended as a preferred treatment option for some selected patients with GCPM. Intraperitoneal free cancer cells were recognized as the pathological cause of PM and the primary target for intraperitoneal chemotherapy. There were a lot of evidence demonstrating that HIPEC could effectively eradiate intraperitoneal free cancer cells and prolong overall survival in GCPM. However, there are still no standard HIPEC protocols. This review summarized the current HIPEC regimens used in GCPM from a literature search, trying to conclude the optimal HIPEC in GCPM, and indicate the future direction of HIPEC study. Moreover, the new data on the exploration of HIPEC in GCPM at Shijitan Hospital, Capital Medical University was shared. In conclusion, there was not enough evidence from publications and our own experience to conclude a recommended HIPEC regimen for GCPM. There is urgent need for standardizing HIPEC protocols worldwide. Accordingly, more international collaborations focusing on pharmacology and HIPEC-related parameters to generate high level evidence are essential.

Conventional peritoneal cytology lacks the prognostic significance of detecting local or peritoneal recurrence in colorectal cancer: An Egyptian experience.

Background and AimColorectal cancer (CRC) accounts for over 8% of all deaths each year, with 1.2 million new cases diagnosed annually worldwide. It represents the seventh most common cancer in Egypt. Early detection of peritoneal metastasis is a major challenge in such cases. It helps with the decision of the immediate application of intraperitoneal chemotherapy after resection. Meta‐analysis studies reported contrast evidence for a possible prognostic role of intraperitoneal free cancer cells (IPCCs) in peritoneal recurrence and survival after curative resection. In this work, we aim to evaluate the prevalence and impact of detecting free malignant cells in peritoneal fluid on survival and local recurrence and to estimate the incidence of peritoneal carcinomatosis (PC) during follow up.MethodsDesign: This was a prospective cohort study. Settings: From June 2016 to December 2018, samples were collected from 104 patients who underwent abdominal surgery for colorectal cancer in the Egyptian National Cancer Institute. A total of 96 Egyptian CRC patients who underwent curative resection were enrolled. Intraoperative peritoneal lavage was performed to detect IPCC by conventional cytology. Patients with no residual tumor after surgery and no evidence of PC were followed up for a median 14 months. The cumulative 12‐month overall survival rate for patients with IPCC was 100% versus 86% for patients with negative cytology.ResultsOur results demonstrated that the prevalence of IPCC in the peritoneal lavage was 11.5%. Peritoneal and local recurrence occurred at a higher rate in patients with cytology positive lavage (9.1% vs 6.3% and 9.1% vs 3.8%, respectively), although this was statistically insignificant. Distant metastasis occurred significantly in patients with positive cytology (45.5% vs 8.9%) with P‐value <0.001.The conventional cytology technique has a high specificity but less sensitivity.ConclusionsThe presence of IPCC using conventional cytology was not an independent prognostic factor for the development of PC or survival.

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.

Prognostic impact of peritoneal cytology in patients with established peritoneal carcinomatosis treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Background: The presence of intraperitoneal free cancer cells in locally-advanced resectable cancers of gastrointestinal and ovarian origin without visible peritoneal carcinomatosis (P0Cy1) has a profound impact on prognosis. Our objective is to explore the possible prognostic impact of peritoneal cytology washing (Cy status) in patients with established macroscopic carcinomatosis (P1).

Diagnostic value of negative enrichment and immune fluorescence in situ hybridization for intraperitoneal free cancer cells of gastric cancer.

ObjectiveTo explore the intraperitoneal free cancer cell (IFCC) detection value of negative enrichment and immune fluorescence in situ hybridization (NEimFISH) on chromosomes (CEN) 8/17. MethodsTo verify the reliability of NEimFISH, 29 gastric cancer tumors, their adjacent tissues and greater omental tissues were tested. Our study then included 105 gastric cancer patients for IFCC. We defined patients as IFCC-positive if a signal was detected, regardless of the detailed cancer cell numbers. A comparison of clinicopathological features was conducted among IFCC groups. We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods. The comparison of IFCC number was also conducted among different groups.ResultsA cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97% of malignant tissue samples in our study. Compared to intestinal gastric cancer, patients with diffuse gastric cancer tended to have more IFCCs (6 vs. 4, P=0.002). The IFCC counts were often higher in the lymphovascular invasion positive group than negative group (3 vs. 1, P=0.022). All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH. When compared to conventional cytology and paraffin pathology, NEimFISH had a higher IFCC positive rate (68.9%) and higher one-year peritoneal recurrence predictive value with area under the curve (AUC) of 0.922. ConclusionsGastric cancer could be effectively diagnosed by NEimFISH. The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer. NEimFISH is a reliable detection modality with a higher positive detection rate, higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.

Detection of carcinoembryonic antigen in peritoneal fluid of patients undergoing laparoscopic distal gastrectomy with complete mesogastric excision.

Surgery for gastric cancer may result in free intraperitoneal cancer cells. This study aimed to determine whether laparoscopic gastrectomy with complete mesogastric excision (D2 + CME) reduces the number of free intraperitoneal cancer cells. Patients with gastric cancer who had a conventional D2 or D2 + CME laparoscopic distal gastrectomy between April 2015 and February 2017 were included in the study. Intraoperative peritoneal washings were collected before and after tumour resection. Reverse transcriptase-quantitative real-time PCR for carcinoembryonic antigen (CEA) was used to assess the presence of gastric cancer cells. Eighty-five patients underwent conventional D2 lymphadenectomy and 76 had the D2 + CME procedure. Of 161 peritoneal fluid samples obtained before gastrectomy, 137 (D2, 72; D2 + CME, 65) had low CEA expression indicative of no cancer cells. After gastrectomy, high CEA expression was detected in 23 of the 72 samples (32 per cent) from patients in the D2 group, and in ten of the 65 samples (15 per cent) from the D2 + CME group. In the overall cohort, mean CEA expression level after gastrectomy was lower in the D2 + CME group than in the D2 group (P = 0·0038). In patients with low CEA expression before gastrectomy, disease-free survival in the D2 + CME group was better than that in the D2 group (P = 0·033). Laparoscopic distal gastrectomy with complete mesogastric excision reduces the number of free intraperitoneal cancer cells and is associated with a better disease-free survival than conventional D2 gastrectomy.

Long-term outcome of a randomized phase III trial exploring the significance of extensive intraoperative peritoneal lavage in addition to standard treatment for ≥ T3 resectable gastric cancer: CCOG 1102.

1 Background: Extensive intraoperative peritoneal lavage (EIPL) for gastric cancer reportedly improved survival by physically removing and reducing intraperitoneal-free cancer cells in a small-scale randomized trial (Ann Surg 2009). To confirm this, we conducted a multicenter randomized Phase III trial. Methods: Eligibility criteria: (i) histologically confirmed primary gastric adenocarcinoma, (ii) clinically T3(SS), T4a(SE) or T4b(SI), (iii) clinically M0, and (iv) scheduled for total or distal gastrectomy. Patients were intraoperatively randomized to either the EIPL group or the non-EIPL group after confirming the ≥T3 status and resectability. In the EIPL group, peritoneal lavage was conducted at least 10 times using 1L of saline before the closure of the abdomen. In the non-EIPL group, the lavage was conducted with ≤3L of saline. The primary end-point was disease-free survival (DFS). To detect the difference of 15% in 3-year DFS with a both-sided alpha of 5% and 80% power, the planned sample size was 300 cases. This study was registered as UMIN000005907. Results: Between July 2011 and January 2014, 314 patients were registered from 15 institutions. After excluding the R1/R2 resection cases, 295 patients (145 in the EIPL group and 150 in the non-EIPL group) were analyzed. There were no significant differences between the groups in clinicopathologic characteristics. The median volume of saline for the peritoneal lavage was 10.0 L (10 - 12) for the EIPL group and 3.0 L (1 - 4) for the non-EIPL group. No difference was observed in the incidence of postoperative complications. The 3-year DFS was 63.9% in the EIPL group and 59.7% in the non-EIPL group (p = 0.25, Hazard ratio 0.81 [95% CI 0.57-1.16]). The overall survival rate of the EIPL group and non-EIPL group were 75.0%, 73.7% (3 years), and 62.5%, 57.1% (5 years), respectively (p = 0.65). In the subset analysis, no subgroup with significant difference in survival was identified. Conclusions: Although EIPL for advanced gastric cancer was safe and suggested some efficacy, the primary endpoint designed based on the previous small-scale trial was not met. Clinical trial information: 000005907.

Is detection of intraperitoneal exfoliated tumor cells after surgical resection of rectal cancer a prognostic factor of survival?

BackgroundThe prognostic significance of free cancer cells detected in peritoneal fluid at the time of rectal surgery remains unclear. A substantial number of patients will develop metastatic disease even with successful local treatment. This prospective non-randomized study investigated the prognostic value of intraperitoneal free cancer cells harvested in peritoneal lavage after surgery for rectal cancer. Mutational hotspots in mitochondrial DNA were examined as potential molecular signatures to detect circulating intraperitoneal free cancer cells when present in primary tumor and in lavage.MethodsPoint mutations in mitochondrial DNA amplifications were determined in primary tumors and corresponding exfoliated intraperitoneal free cancer cells in lavage from 191 patients with locally advanced rectal cancer scheduled for radical treatment. Mitochondrial DNA target sequences were amplified by polymerase chain reaction and base substitutions were detected by denaturant, cycling temperature capillary electrophoresis. Detection of intraperitoneal free cancer cells was correlated to survival.ResultsOf 191patients analyzed, 138 (72%) were identified with somatic mitochondrial point mutations in rectal cancer tumors. From this fraction, 45 patients (33%) had positive lavage fluid with corresponding somatic mtDNA point mutations in lavage representing circulating intraperitoneal free cancer cells. There was no significant survival difference between patients identified with or without somatic mitochondrial DNA point mutations in the corresponding lavage.ConclusionSomatic mitochondrial DNA point mutations identified in primary rectal tumors enable detection of circulating intraperitoneal free cancer cells in lavage fluid.Intraperitoneal free cancer cells harvested from lavage immediately after surgery for rectal cancer does not represent an independent prognostic factor on survival.

Laparoscopic D2 gastrectomy with complete mesogastrium excision (D2+CME) to reduce cancer leak from mesogastrium in patients with advanced gastric cancer.

18 Background: The mechanism underlying tumor recurrence following curative surgery remains unclear. It is believed that intraperitoneal free cancer cells leaked into peritoneal cavity during curative surgery play an important role. In gastric cancer, new strategies should be established towards preventing leakage of cancer cells from the primary tumor involved tissues. Our previous research demonstrated the existence of disseminated cancer cells in the mesogastrium, and we proposed laparoscopic D2 lymphadenectomy plus complete mesogastrium excision (D2+CME) as an optimized surgical procedure for advanced gastric cancer (AGC). By dissecting along the surgical planes and embryonic boundary of mesogastrium, D2+CME is repeatable with less blood lost and improved short-term surgical outcomes. In this study, we further evaluated the oncological effect of D2+CME based on the detection of “cancer leak”. Methods: The peritoneal washings were collected prior to and after tumor resection from 45 patients who underwent D2+CME (D2+CME group) and 46 patients who underwent conventional D2 lymphadenectomy (D2 group). RT-PCR was used to determine the presence of cancer cells. Positive samples are defined as those with CEA mRNA level over threshold (cutoff value). Results: Of 91 peritoneal washing samples obtained before gastrectomy, 84 (41 in D2+CME; 43 in D2 alone) showed no presence of cancer cell. After gastrectomy, CEA positive was detected in 17 of 43 (39.5%) samples with D2 group, however, only 5 of 41 (12.2%) samples in D2+CME group detected positive CEA. The average level of CEA expression in D2+CME group was also significant lower than that in D2 group after gastrectomy (p &lt; 0.05). Presence of “cancer leak” was closely associated with pT stage and surgical procedures. The DFS of patients with CEA positive after gastrectomy was significantly poorer than that of patients with CEA negative (p &lt; 0.05). Conclusions: LaparoscopicD2+CME could reduce the leakage of free cancer cells from the envelop of mesogastrium into the peritoneal cavity during radical gastrectomy, and thus, it might potentially increase the prognosis of AGC patients. Clinical trial information: NCT01978444.

Phase II study of intraperitoneal paclitaxel plus S-1/paclitaxel for gastric cancer with positive peritoneal cytology: CY-PHOENIX trial.

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.

TREATMENT OUTCOMES OF PROXIMAL GASTRIC CANCER DEPENDING ON THE EXTENT OF SURGICAL RESECTION

Surgical resection for proximal gastric cancer remains an important problem of oncology. Personalized surgical management represents one of the main challenges in treating gastric cancer. The aim of the study was to analyze surgical outcomes of proximal gastric cancer depending on the tumor spread, extent of surgery and the presence of intraperitoneal free cancer cells. Material and Methods. The study included 68 patients with morphologically verified locally advanced proximal gastric cancer. The patients were divided into 2 groups. Group I consisted 37 patients, who underwent total gastrectomy of 31 patients; Group II comprised who underwent proximal subtotal gastrectomy. Results. The overall three-year survival was 48.7 ± 16.9 % in Group I and 66.4 ± 13.2 % in Group II patients. The 3-year progressive-free survival rate was 51.5 ± 18.5 % after proximal subtotal gastrectomy and 34.8 ± 25.6 % after total gastrectomy. The presence of tumor cells in the abdominal cavity was proven to lead to early carcinomatosis. Thus, the 2-year overall survival rate was 26.7 ± 42.8 % in patients in whom free cancer cells were found in peritoneal washings and 69.8 ± 9.0 % in patients with negative cytology findings from washings. Conclusion. Proximal subtotal gastrectomy provides better survival rates compared to total gastrectomy in patients with locally advanced proximal gastric cancer. Local spread of the tumor, which is known to significantly increase the risk of lymph node metastasis and contamination of the peritoneal cavity with cancer cells, is one of the main unfavorable prognostic factors.

Intraperitoneal free cancer cells in gastric cancer: pathology of peritoneal carcinomatosis and rationale for intraperitoneal chemotherapy/hyperthermic intraperitoneal chemotherapy in gastric cancer.

Peritoneal carcinomatosis (PC) is one of the most common causes of death in gastric cancer patients. Intraperitoneal free cancer cells (IFCCs) play a very important role in forming PC, but the administration of intraperitoneal chemotherapy (IPC) and/or hyperthermic intraperitoneal chemotherapy (HIPEC) could be an effective treatment for IFCCs. This review focuses on the origin of IFCCs, the mechanism of PC formatting, the rationale of IPC/HIPEC, and the current clinical trials on IPC/HIPEC to treat advanced gastric cancer patients.