Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the "Lancet Gastroenterol Hepatol" (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m²) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the " Lancet Gastroenterol Hepatol " (COLOPEC). Regrettably, no significant difference was observed in 18?month peritoneal metastasis?free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues:(1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0?2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5?8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact. (3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high?dese oxaliplatin (460 mg/m2) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC?06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the " Lancet Gastroenterol Hepatol " (COLOPEC). Regrettably, no significant difference was observed in 18?month peritoneal metastasis?free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues:(1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0?2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5?8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact. (3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high?dese oxaliplatin (460 mg/m2) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC?06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Objective To investigate the effect of hyperthermic intraperitoneal perfusion and cisplatinon apoptosis in human ovarian cancer cells.Methods Two human ovarian cancer cells (OVCAR-3,A2780) were divided into control group,cisplatin group,hyperthermia group and thermo-chemotherapy group;microscopy was used to observe the morphological changes of the four groups;AO/GV stain and flow cytometry(FCM) was used to analyze cell apoptosis;Apoptosis related genes caspase7,caspase8 and Bax in ovarian cancer cells were detected by fluorescence quantitative PCR.Results Inverted microscopy observeed that the ovarian cancer cells retracted and suspended partially in the cisplatin group and hyperthermia group,especially in the thermo-chemotherapy group.After AO/GV staining,the apoptotic cells were increased in the cisplatin group and hyperthermia group compared with the control group,and the thermo-chemotherapy group was more than cisplatin group and hyperthermia group.FCM results indicated that the proportion of cells apoptosis were higher in the cisplatin group and hyperthermiagroup,the thermo-chemotherapy group is the higher than the all other groups(P＜0.05).q-PCR results showed that in the thermo-treatment group the expression of pro-apoptotic genes,including caspase3,caspase6,caspase7,caspase8,caspase9,Bax,Bak and Bid,was significantly higher than other groups,apoptosis inhibitory gennes,such as Bcl-2,Bcl-xL,Mcl-1,c-FLIP,was significantly decreased than the others.Conclusions Cisplatin plus hyperthermia can promote the apoptosis in ovarian cancer cells.

To study the role and molecular mechanism of epigallocatechin gallate (EGCG) in reversing drug-resistance to 5-fluorouracil (5-FU) in gastric cancer drug-resistant cell line SGC-7901/5-FU.

METHODSDrug-resistance gastric cancer cell line (SGC-7901/5-FU) was established by high doses of repeated impact joint drug concentration increment methods. The cell viability of the parent cell line and the drug-resistance cell line were determined by standard MTT assay. Cell survival rate of drug-resistance was calculated by the formula [(Aof the treatment group / Aof the control group) × 100%]. Cell half inhibitory concentration (IC) and resistance index (RI) were calculated by the Graphpad prime 6.0 software(RI=ICvalue of drug-resistance cells / ICvalue of parent cells). The apoptosis rate of SGC-7901/5-FU cells was quantified by flow cytometry after staining with annexin-V and PI. Western blot was used to detect the protein expression of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) and apoptosis-related proteins (PARP, Survivin, Bax and bcl-2).

RESULTSICvalue was significantly increased in drug-resistant cells compared with parental cells [(64.7±3.9) mg/L and (4.1±0.3) mg/L, respectively, t=26.46, P=0.000], and the RI was 15.6. Proliferation activity in the drug-resistant cells was higher than that in parental cells at different 5-FU concentrations (all P<0.05). In drug-resistant cells, the ICvalue of 5-FU combined with EGCG group obviously decreased compared with 5-FU group [(7.3±0.1) mg/L and (63.1±1.4) mg/L respectively, t=40.84, P=0.000], and the RI was 0.12. Proliferation activity in drug-resistant cells was significantly decreased after EGCG treatment at different 5-FU concentrations (all P<0.05). Cell apoptosis rates in control group, 5-FU group, EGCG group and 5-FU combined with EGCG group were (3.0±1.0)%, (7.0±1.3)%, (6.0±1.2)% and (18.0±1.4)%, while apoptosis rate in 5-FU combined with EGCG group was significantly higher than those of other 3 groups(F=129.5, P=0.000). Western blot revealed that after EGCG treatment, the expression levels of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) in the drug-resistant cell line SGC-7901/5-FU decreased significantly; the expression levels of apoptosis marker protein PARP and pro-apoptotic protein Bax increased significantly; and the expression levels of anti-apoptotic protein Survivin and Bcl-2 decreased significantly (all P<0.05).

CONCLUSIONEGCG can reduce the resistance of gastric cancer resistant cell line SGC-7901/5-FU, whose role may be via the inhibition of the expression of drug-resistance-related proteins, and the elevation of the protein expression ratio of PARP/Survivin and Bax/Bcl-2.

Anticarcinogenic Agents ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Drug Resistance, Neoplasm ; Fluorouracil ; pharmacology ; Humans ; Stomach Neoplasms ; drug therapy ; pathology ; bcl-2-Associated X Protein

Objective To investigate the measurement , feasibility and clinic effect of hyperthermic intraperitoneal chemotherapy (HIPEC) guided by B ultrasound in the treatment of malignant ascites from peritoneal carcinomatosis. Methods From July 2011 to June 2013, B ultrasound-guided approach was used to perform HIPEC on 36 patients affected by malignant ascites secondary to peritoneal carcinomatosis. Every patient underwent HIPEC for three times , by way of continuous circulatory perfusion into peritoneal cavity with saline at 400 ~ 600 mL/min and intraperitoneal perfusion with 5-FU mitomycin-C and cisplatin for 90 minutes with an inflow temperature of (43 ± 0.2)℃. These patients were followed up for a long term. Results Intraoperative course was uneventful in all cases. Complete clinical regression of ascites and related symptoms was achieved in all the 26 patients, partial regression achieved in 8 patients, and no curative effect achieved in 2 cases. The acquired total clinic effectiveness was 94.44%. No postoperative deaths and complication related to the procedure occurred in this study. The KPS grades of patients rose (P < 0.001), the level of tumor markers decreased, including CA199 (P < 0.001), CEA (P < 0.001), CA125 (P = 0.003). Conclusion HIPEC guided by B ultrasound appears to be a safe, feasible and effective procedure for the treatment of debilitating malignant ascites from unresectable peritoneal carcinomatosis , which would have a clinic good perspective in future.

Objective To investigate the factors affecting the survival and prognosis of patients with stage Ⅲ～ Ⅳgastric cancers.Methods A total of 156 cases of Ⅲ ～ Ⅳ gastric cancer was studied retrospectively from September 1,2006 to December 31,2012.Kaplan-Meier analysis,Log-rank univariate analysis,Cox proportional hazards model analysis were used to analyze survival and prognostic factors.Results Twelve cases were lost,to the end of the follow-up,22 cases were alive.The median survival time was 29.3 months.1-year,3-year,and 5-year overall survival rates were 83.3％,37.8％,and 21.2％,respectively.Univariate analysis showed that tumor size,tumor node metastasis (TNM) staging,curative resection,hyperthermic intraperitoneal perfusion chemotherapy (HIPEC),and postoperative chemotherapy were correlated with prognosis (P ＜0.05 for all).Multivariate analysis showed that TNM staging,curative resection,HIPEC,and postoperative chemotherapy were independent prognostic factors (P ＜ 0.01 for all).Conclusions TNM staging,curative resection,hyperthermic intraperitoneal perfusion chemotherapy and postoperative chemotherapy are the independent factors affecting the prognosis of stage Ⅲ～ Ⅳ gastric cancer after resection.Hyperthermic intraperitoneal perfusion chemotherapy and postoperative chemotherapy can improve their survival.

BACKGROUND:Mouse pluripotent stem cel s are induced to differentiate into insulin-secreting cel s that can effectively improve blood glucose levels in diabetic mice. OBJECTIVE:To detect mRNA and protein levels of insulin-like cel clusters from induced pluripotent stem cel s and to investigate the function of insulin-secreting cel s in vitro and in vivo. METHODS:Mouse induced pluripotent stem cel s cultured in vitro were induced to differentiate into insulin-secreting cel s using combined inducers through three stages. The morphology of endodermal cel s, islet-derived progenitor cel s and mature islet cel s in each stage was observed and relative gene expression levels were detected by PCR. Mature insulin-like cel clusters underwent dithizone staining and functions of insulin released in vitro were observed by ELISA assay. Final y, the insulin-secreting cel s were transplanted into the subrenal capsule of diabetic mice, and then blood glucose levels were observed. RESULTS AND CONCLUSION:The mature spherical insulin-like cel clusters were successful y obtained in vitro, which were in iron red by dithizone staining, and expression of insulin mRNA was determined by PCR. The insulin-like cel clusters could secrete insulin in response to various blood glucose levels by ELISA assay. In addition, after the cel s clusters were transplanted into the subrenal capsule of mice with type 1 diabetes, the blood glucose levels were marbedly improved.