Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives

BACKGROUND Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects.The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy(HIPEC)has been shown to increase survival rates in these patients.Despite these advancements,debates persist regarding the magnitude of survival improvement attributed to this treatment modality.The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis,and it took a comparative analysis of patients exhibiting positive and negative cytological findings.Between April 2013 and March 2020,84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts:HIPEC(20 patients with peritoneal metastasis),cytology-positive(23 patients without peritoneal nodules but with positive wash cytology),and cytology-negative(41 patients with advanced gastric cancer,no peritoneal nodules,and negative wash cytology).The HIPEC cohort underwent gastrectomy with HIPEC,while the cytology-positive and cytology-negative groups received gastrectomy alone.The demographic,pat-hological,and survival data of the groups were compared.RESULTS The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss.Nevertheless,the complication rates were consistent across all three groups.Median survival in the HIPEC group was 20.00±4.89 months,with 1-year,2-year,and 3-year overall survival rates of 73.90%,28.70%,and 9.60%,respectively.These figures paralleled the survival rates of the cytology-positive group(52.20%at 1 year,28.50%at 2 years,and 19.00%at 3 years).Notably,47%of patients experienced peritoneal recurrence.CONCLUSION HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis,mirroring the outcomes in cytology-positive patients.However,peritoneal recurrence remained high.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.

Cytoreductive surgery and hyperthermic intraperitonealchemotherapy in gastric cancer

Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery( CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in longterm survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.

Prediction of lymph node metastasis and sentinel node navigation surgery for patients with early-stage gastric cancer

Accurate prediction of lymph node(LN) status is crucially important for appropriate treatment planning in patients with early gastric cancer(EGC). However,consensus on patient and tumor characteristics associated with LN metastasis are yet to be reached. Through systematic search,we identified several independent variables associated with LN metastasis in EGC,which should be included in future research to assess which of these variables remain as significant predictors of LN metastasis. On the other hand,even if we use these promising parameters,we should realize the limitation and the difficulty of predicting LN metastasis accurately. The sentinel LN(SLN) is defined as first possible site to receive cancer cells along the route of lymphatic drainage from the primary tumor. The absence of metastasis in SLN is believed to correlate with the absence of metastasis in downstream LNs. In this review,we have attempted to focus on several independent parameters which have close relationship between tumor and LN metastasis in EGC. In addition,we evaluated the history of sentinel node navigation surgery and the usefulness for EGC.

Regional but fatal: Intraperitoneal metastasis in gastric cancer

Peritoneal carcinomatosis appears to be the most common pattern of metastasis or recurrence and is associated with poor prognosis in gastric cancer patients. Many efforts have been made to improve the survival in patients with peritoneal metastasis. Hyperthermic intraperitoneal chemotherapy remains a widely accepted strategy in the treatment of peritoneal dissemination. Several phase Ⅱ-Ⅲ studies confirmed that the combined cytoreducitve surgery and hyperthermic intraperitoneal chemotherapy resulted in longer survival in patients with peritoneal carcinomatosis. In addition,proper selection and effective regional treatment in patients with high risk of peritoneal recurrence after resection will further improve prognosis in local advanced gastric cancer patients.

Risk factors for lymph node metastasis and evaluation of reasonable surgery for early gastric cancer

AIM: To give the evidence for rationalizing surgical therapy for early gastric cancer with different lymph node status. METHODS: A series of 322 early gastric cancer patients who underwent gastrectomy with more than 15 lymph nodes retrieved were reviewed in this study. The rate of lymph node metastasis was calculated. Univariate and multivariate analyses were performed to evaluate the independent factors for predicting lymph node metastasis. RESULTS: No metastasis was detected in No.5, 6 lymph nodes (LN) during proximal gastric cancer total gastrectomy, and in No.10, 11p, 11d during for combined resection of spleen and splenic artery and in No.15 LN during combined resection of transverse colon mesentery. No.11p, 12a, 14v LN were proved negative for metastasis. The global metastastic rate was 14.6% for LN, 5.9% for mucosa, and 22.4% for submucosa carcinoma, respectively. The metastasis in group Ⅱ?was almost limited in No.7, 8a LN. Multivariate analysis identified that the depth of invasion, histological type and lymphatic invasion were independent risk factors for LN metastasis. No metastasis from distal cancer (≤ 1.0 cm in diameter) was detected in group Ⅱ?LN. The metastasis rate increased significantly when the diameter exceeded 3.0 cm. All tumors (≤ 1.0 cm in diameter) with LN metastasis and mucosa invasion showed a depressed macroscopic type, and all protruded carcinomas were > 3.0 cm in diameter. CONCLUSION: Segmental/subtotal gastrectomy plus D1/D1 + No.7 should be performed for carcinoma (≤ 1.0 cm in diameter, protruded type and mucosa invasion).Subtotal gastrectomy plus D2 or D1 + No.7, 8a, 9 is the most rational operation, whereas No.11p, 12a, 14v lymphadenectomy should not be recommended routinely for poorly differentiated and depressed type of submucosa carcinoma (> 3.0 cm in diameter). Total gastrectomy should not be performed in proximal, so does combined resection or D2+/D3 lymphadenectomy.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis:A multicenter propensity scorematched cohort study

Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.

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

AIM To investigate the significance of heat shock protein 110(HSP110) in gastric cancer(GC) patients with peritoneal metastasis undergoing hyperthermochemotherapy.METHODS Primary 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 hyptherthermochemosensitivity was assessed in vitro in the MKN45 GC cell line using the HSP inhibitor KNK437. RESULTS HSP110 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 ℃ in vitro. Comparison of MKN45 cell proliferation in the presence and absence of KNK437 at 43 ℃, 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.CONCLUSION The 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.

Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis.Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier.Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients.Patient selection for this multimodal approach is one of the most critical issues,and calls for interdisciplinary evaluation by radiologists,medical and surgical oncologists,and anaesthetists.This article sets forth criteria for selection of gastric cancer patients suffering from peritoneal carcinomatosis.

Intraperitoneal Chemotherapy as a Multimodal Treatment for Gastric Cancer Patients with Peritoneal Metastasis

Peritoneal metastasis of gastric cancer is mainly caused by the dispersion of free cancer cells from the serosal surface of the invaded stomach, from surgically transected lymphatic channels, and from tumor cell-containing blood from the primary lesion into the peritoneal cavity. Intraperitoneal chemotherapy (IPC) combined with surgery has performed for the prevention and treatment of peritoneal metastasis in gastric cancer. The efficacy of this technique is influenced by the pharmacokinetic advantage achievable with the anticancer drug, timing of administration, combination with hyperthermia, and tumor volume. The pharmacokinetic advantage for peritoneal cavity exposure relative to peripheral circulation by intraperitoneal delivery for drugs including cisplatin (10-fold advantage), mitomycin C (20- to 30-fold advantage), docetaxel (500-fold advantage), and paclitaxel (1000-fold advantage) has been confirmed. To avoid uneven drug distribution in the peritoneal cavity and the re-growth of residual tumor, it seems to be reasonable to perform IPC perioperatively;however, early perioperative intraperitoneal chemotherapy (EPIC) has a relatively high morbidity rate compared with intraoperative IPC. Hyperthermia has both cytotoxicity of itself and a synergistic effect with anticancer drugs, especially mitomycin C. In the adjuvant setting, patients with either hyperthermic intraperitoneal chemotherapy (HIPEC) or EPIC showed a significant improvement of survival compared to those with surgery alone. In addition, extensive intraoperative peritoneal lavage (EIPL) seems also to be a reasonable method to reduce free cancer cells in the peritoneal cavity. For the treatment of peritoneal metastasis, cytoreductive surgery which achieves R0 or R1 resection followed by IPC has demonstrated a survival benefit, whereas gross residual tumor (R2) treated by IPC has shown poor prognosis. Extensive cytoreductive surgery, such as peritonectomy, followed by IPC achieved long-term survival for selected patients, though this aggressive procedure led to high morbidity and mortality rates. It seems that combined chemotherapy (systemically and intraperitoneally) followed by conversion surgery can be expected to be a powerful procedure for the patients with gross peritoneal tumors.

Molecular targeting therapy using bevacizumab for peritoneal metastasis from gastric cancer

AIM: To clarify the significance of vascular endothelial growth factor(VEGF) in peritoneal metastasis from gastric cancer, using the gastric cancer cell line MKN-45 compared with the high potential peritoneal dissemination gastric cancer cell line MKN-45 P. METHODS: The supernatant of culture medium of MKN-45 cells or MKN-45 P cells was collected and the concentrations were measured of various cytokines, matrix metalloproteinases, growth factor and angiogenic factors, including VEGF. We performed an initial pilot study to explore whether bevacizumab, a humanized monoclonal antibody against VEGF, had any suppressive effect on the peritoneal dissemination from gastric cancer in an experimental nude mouse modelof peritoneal metastasis. RESULTS: The concentrations of interleukin-6(IL-6), IL-8, VEGF and matrix metalloproteinase-2 protein in the culture supernatant were each significantly higher than each of those for MKN-45. In the in vivo study, the volume of ascites and the mitotic index were significantly lower in the therapy group than in the nontherapy group. The survival curve of the therapy group was significantly higher than that of the non-therapy group. These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer. CONCLUSION: Findings suggested that bevacizumab for inhibiting VEGF could suppress peritoneal dissemination from gastric cancer.

Complications and risk factors for complications of implanted subcutaneous ports for intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis

Objective:Intraperitoneal(IP)chemotherapy through subcutaneous port is an effective treatment for gastric cancer(GC)patients with peritoneal metastasis(PM).The objective of this study is to assess the port complications and risk factors for complications in GC patients with PM.Methods:In retrospective screening of 301 patients with subcutaneous ports implantation,249 GC patients with PM who received IP chemotherapy were screened out for analysis.Port complications and risk factors for complications were analyzed.Results:Of the 249 analyzed patients,57(22.9%)experienced port complications.Subcutaneous liquid accumulation(42.1%)and infection(28.1%)were the main complications,and other complications included port rotation(14.1%),wound dehiscence(12.3%),inflow obstruction(1.7%)and subcutaneous metastasis(1.7%).The median interval between port implantation and occurrence of complications was 3.0 months.Eastern Cooperative Oncology Group(ECOG)performance status[odds ratio(OR),1.74;95%confidence interval(95%CI),1.12-2.69],albumin(OR,3.67;95%CI,1.96-6.86),implantation procedure optimization(OR,0.33;95%CI,0.18-0.61)and implantation groups(OR,0.37;95%CI,0.20-0.69)were independent risk factors for port complications(P<0.05).ECOG performance status was the only factor that related to the grades of port complications(P=0.016).Conclusions:Port complications in GC patients who received IP chemotherapy are manageable.ECOG performance status,albumin,implantation procedure and implantation group are independent risk factors for port complications in GC patients with PM.

Standard Prophylactic Strategy against Peritoneal Dissemination Metastasis in Gastric Cancer

Peritoneal carcinomatosis is the most frequent pattern of metastasis and recurrence in patients with gastric cancer, and the prognosis of those patients with peritoneal metastasis is extremely poor. Once peritoneal metastasis is formed, it is extremely difficult to overcome. EIPL (extensive intraoperative peritoneal lavage) is a quite useful and practical adjuvant surgical technique for the gastric cancer patients who are likely to suffer from peritoneal recurrence. EIPL includes 10 times of an extensive shake and wash of abdominal cavity with saline followed by the complete aspiration of the fluid after potentially curative operation, which is supposed to have an amazing cyto-reduction power. The purpose of this article is to review the effect of EIPL on prevention of peritoneal recurrence in the patients with peritoneal free cancer cells and to evaluate its validity as a standard prophylactic strategy against peritoneal recurrence in gastric cancer.

Comprehensive treatment for the peritoneal metastasis from gastric cancer

Recently, a novel comprehensive treatment consisting of cytoreductive surgery(CRS) and perioperative chemotherapy(POC) was developed for the treatment of peritoneal metastasis(PM) with a curative intent. In the treatment, the macroscopic disease is completely removed by the peritonectomy techniques in combination with POC. This article reviews the results of the comprehensive treatment for PM from gastric cancer, and verifies the effects of CRS and POC, including neoadjuvant chemotherapy(NAC) and hyperthermic intraoperative intraperitoneal chemotherapy(HIPEC). Completeness of cytoreduction, peritoneal carcinomatosis index(PCI) less than the threshold levels after NAC,absence of ascites, cytologic status, pathologic response after NAC are the independent prognostic factors. Among these prognostic factors, PCI threshold level is the most valuable independent prognostic factor. After staging laparoscopy, patients with PM from gastric cancer are recommended to treat with NAC before CRS. After NAC, indication for CRS is determined by laparoscopy. The indications of the comprehensive treatment are patients with PCI less than the threshold levels, negative cytology, and responders after NAC. Patients satisfy these factors are the candidates for the CRS and HIPEC.

HAND2-AS1,PRKAA2 and VLDLR predict the risk of peritoneal metastasis in gastric cancer of different Lauren types based on STEPP analysis

The peritoneum is the most common site of recurrence of gastric cancer(GC).Early occult peritoneal metastasis is difficult to detect by imaging examination.Stratifying the risk of peritoneal metastasis in patients with different Lauren subtypes is of great clinical value.We performed a univariate Cox regression to identify those genes with prognostic value of overall survival(OS)and peritoneal-specified disease-free survival(psDFS)from the Gene Expression Omnibus database.The candidate genes were screened by the Subpopulation Treatment Effect Pattern Plot(STEPP)method.Propensity score matching(PSM)analysis was used to reduce the interference of confounders on the results.Based on the optimal cut-off values determined by the STEPP method,we found overexpression of three genes(HAND2-AS1,PRKAA2,and VLDLR)was correlated with shorter 1-year psDFS among patients with diffuse-type than that of patients with intestinal-type GC,and it is highly significant.Gene Set Enrichment Analysis(GSEA)potentially suggested that the three genes promote the early occurrence of peritoneal metastasis in patients with diffuse-type GC through glucose metabolism-related pathways.These three genes may be potential biomarkers.They can be used to assess the risk of peritoneal metastases to guide treatment decisions and follow-up strategies.

Predictive factors of lymph node metastasis in intramucosal poorly differentiated early gastric cancer and their impact on the laparoscopic surgery

Objective The aim of this study was to identify clinicopathological factors predictive of lymph node metastasis (LNM) in intramucosal poorly differentiated early gastric cancer (EGC), and further to expand the possibility of using laparoscopic surgery for the treatment of intramucosal poorly differentiated EGC.

Risk of lymph node metastasis in mixed-type early gastric cancer determined by the extent of the poorly differentiated component

AIM: To predict the rate of lymph node(LN) metastasis in diffuse- and mixed-type early gastric cancers(EGC) for guidelines of the treatment.METHODS: We reviewed 550 cases of EGC withdiffuse- and mixed-type histology. We investigated the clinicopathological factors and histopathological components that influence the probability of LN metastasis, including sex, age, site, gross type, presence of ulceration, tumour size, depth of invasion, perineural invasion, lymphovascular invasion, and LN metastasis status. We reviewed all slides and estimated the proportions of each tumour component; pure diffuse type, mixed-predominantly diffuse type(diffuse > intestinal type), mixed-predominantly intestinal type(intestinal > diffuse type), and mixed diffuse = intestinal type. We calculated the extents of the respective components.RESULTS: LN metastasis was observed in 12.9%(71/550) of early gastric cancers cases [15/288 mucosal EGCs(5.2%) and 56/262 submucosal EGCs(21.4%)]. Of 550 cases, 302 were diffuse-type and 248 were mixed-type EGCs. Of 248 mixed-type EGCs, 163 were mixed-predominantly diffuse type, 82 were mixed-predominantly intestinal type, and 3 were mixed diffuse = intestinal type. Mixed-type cases with predominantly diffuse type histology showed a higher frequency of LN metastasis(20.2%) than cases of pure diffuse type(9.3%) and predominantly intestinal type(12.2%) histology. We measured the dimensions of each component(intestinal and diffuse type) to determine the association of the extent of each component with LN metastasis in mixed-type gastric carcinoma. The total tumour size and the extent of poorly differentiated components was associated with LN metastasis, while that of signet ring cell components was not.CONCLUSION: We recommend careful identification and quantitative evaluation of mixed-type early gastric cancer components after endoscopic resection to determine the intensity of the treatment.

Intraperitoneal chemotherapy and its evolving role in management of gastric cancer with peritoneal metastases

Advanced gastric cancer （GC） has been recognized as lethal disease when peritoneal metastases （PM） occurred.There is no standard treatment for advanced GC with PM.Until 1980s,the therapeutic arena for these patients had remained stagnant,with no therapeutic approach having shown a survival gain in GC with PM.However,cytoreductive surgery （CRS） with peritonectomy procedures and intraperitoneal chemotherapy （IPC） promising new combined therapeutic approach to achieve disease control for GC with PM.The recent publications changed the GC with PM treatment landscape by providing an evidence that CRS and IPC led to prolongation in overall survival （OS）.This review will provide an overview of the evolving role of CRS and IPC in the management of advanced GC with PM in the current era.

Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

AIM： To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology （PLC） examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.METHODS： Telomeric repeated amplification protocol （TRAP）-enzyme-linked immunosorbent assay （ELISA） was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen （PCNA） in gastric carcinoma was immunohistochemically examined.RESULTS： The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% （25/60）, and 25.0% （15/60）, respectively. The positive rate of telomerase activity was significantly higher than that Qf PLC in the group of pT, （15/16 vs 9/16, P 〈 0.05）, P1-3 （13/13 vs 9/13, P 〈 0.05） and diffuse type （22/42 vs 13/42, P 〈 0.05）. The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index （PI）, （55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ±10.18 vs 29.15 ±8.31, and 49.82 ± 6.74 vs 24.65 ±7.33, respectively, P 〈 0.05）.CONCLUSION： The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) from gastric cancer has traditionally been considered a terminal progression of the disease and is associated with poor survival out-comes. Positive peritoneal cytology similarly worsens the survival of patients with gastric cancer and treatment options for these patients have been limited. Recent ad-vances in multimodality treatment regimens have led to innovative ways to care for and treat patients with this disease burden. One of these advances has been to use neoadjuvant therapy to try and convert patients with positivecytologyorlow-volume PC to negative cytolo-gy with no evidence of active peritoneal disease.These strategies include the use of neoadjuvant systemic chemotherapy alone,using neoadjuvant laparoscopic heated intraper itoneal chemotherapy(NLHIPEC)after systemic chemotherapy,or using neoadjuvant intra-peritoneal and systemic chemother apy(NIPS)in a bi-dir ectional manner. For patients with higher volume PC,cytoreductive surgery (CRS) and hyperthermic intrape-ritoneal chemotherapy(HIPEC)have been mainstays of treatment. When used together, CRS and HIPEC can improve overall outcomes in properly selected patients,but overall survival outcomes remain unacceptably low.The extent of peritoneal disease, commonly measured by the peritoneal carcinomatosis index (PCI), and the com-pleteness of cytor eduction,has been shown to greatly impact outcomes in patients undergoing CRS and HIPEC.The uses of NLHIPEC and NLHIPEC plus NIPS have both been shown to decrease the PCI and thus increase the opportunity for complete cytoreduction. Newer therapies like pressurized intraperitoneal aerosol chemother apy and immunotherapy, such as catumaxomab, along with improved systemic chemotherapeutic regimens, are being explored with great interest.There is exciting progress being made in the management of PC from gastric can-cer and its’ treatment is no longer futile.