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Objective: To construct a predictive model to assess the completeness of cytoreduction (CC) and help guiding selection for cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) in patients with gastric cancer with peritoneal metastasis (GCPM). Methods: GCPM patients treated with CRS+HIPEC at Beijing Shijitan Hospital were enrolled in this study. The major clinicopathologic and therapeutic characteristics were compared between those with complete CRS (CCRS) and incomplete CRS (ICRS). A nomogram based on a Logistic regression model was constructed for predicting the risk of ICRS. The nomogram was evaluated using area under receiver operating characteristic curve (AUC) and validated using the bootstrap resampling method. The probability of CCRS was predicted using the nomogram. Results: Among the included 125 patients with GCPM, 52 had CC0 cytoreduction and 73 had CC1-3 cytoreduction. The median overall survival (mOS) was 30.0 (95% CI: 16.8-43.3) months in the CC0 group, which was significantly longer than the mOS of 7.3 (95% CI: 5.8-8.8) months in the CC1-3 group (P<0.001). As there were no significant differences in OS among the CC1, CC2, and CC3 groups, CC0 patients were included in the CCRS group and CC1-3 patients were included in the ICRS group. Multivariate Logistic regression demonstrated that the time of peritoneal metastasis development (OR=14, 95% CI: 2.0-97.9, P= 0.008), preoperative tumor markers (TM) (OR=6.5, 95% CI: 2.1-37.8, P=0.037), and peritoneal cancer index (PCI) (OR=1.5, 95% CI: 1.3-1.8, P<0.001) were independent predictive factors for ICRS. The AUC of the nomogram was 0.985. Internal validation displayed good accuracy and consistency between the predictions and the actual observations. The cutoffs of PCI, with the probability of CCRS set at ≥ 50%, were ≤16, ≤12, ≤10, and ≤5 for synchronous GCPM with normal TM, synchronous GCPM with abnormal TM, metachronous GCPM with normal TM, and metachronous GCPM with abnormal TM, respectively. Conclusions: Complete CRS+HIPEC improves the survival of some patients with GCPM. A selection strategy based on PCI combined with the time of peritoneal metastasis development and TM may be a practical way for selecting patients with GCPM eligible for CCRS.
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Peritoneal seeding is one of the three primary forms of cancer metastasis. Significant adverse events are observed in such cases due to inadequate understanding and knowledge of peritoneal cancer. Over the past 30 years, the establishment, improvement, and promotion of surgery-based integrated diagnostic and treatment strategy for peritoneal metastasis have led to an increase in basic, translational, and clinical research. This has resulted in the formation of a new discipline, peritoneal surface oncology. Based on an in-depth understanding of the biological basis, characteristics, and mechanisms of peritoneal metastasis, core clinical diagnostic and therapeutic techniques have been established and improved. From this, the "Ten Milestones" of high-level evidence-based treatment progress has been established. In 2012, the Chinese Journal of Clinical Oncology first launched the "Special Column on Peritoneal Metastasis," urging Chinese clinical oncologists to improve the diagnostic and therapeutic strategies for peritoneal carcinomatosis. Over the past 8 years, with full support from the China Anti-Cancer Association and from oncologists across the country, a comprehensive diagnostic and treatment system for peritoneal metastasis with Chinese characteristics has been established. The publication of the first monograph on this topic in Chinese and the formation of two expert consensuses have led to developments in discipline theory, research platform construction, clinical practice guidelines, and other aspects regarding peritoneal surface oncology in China. Once again, entrusted by the Chinese Journal of Clinical Oncology, we organized the special column "Highlights in Peritoneal Carcinomatosis" aiming to systematically summarize the latest achievements in the field of peritoneal cancer in China, promote the developments in clinical oncology, and provide an overview of the discipline of peritoneal surface oncology.
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Objective:To evaluate the clinical efficacy and safety of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) for patients with advanced ovarian cancer as the first-line surgical treatment.Methods:The ovarian cancer patients with completed clinical data diagnosed as stage Ⅲ C-Ⅳ according to Federation International of Gynecology and Obstetrics (FIGO) who underwent CRS+HIPEC as the first-line treatment from December 2007 to November 2019 in Beijing Shijitan Hospital were retrospectively analyzed. Survival status was analyzed by using Kaplan-Meier method, and prognostic factors were analyzed by using Cox multivariate regression model. The primary endpoints were median overall survival (mOS) time and median progress-free survival (mPFS) time, and the secondary endpoint was safety in perioperative period. Results:Of 100 patients with advanced ovarian cancer, the median follow-up time was 18.4 months, and 75 (75.0%) patients were alive and 25 (25.0%) patients died, of which the mOS time was 87.6 months (95% CI 72.1-103.1 months), and 1-, 2-, 3-, 4- and 5-year survival rate was 94.1%, 77.2%, 68.2%,64.2% and 64.2%, respectively. Univariate analysis showed that the patients with age≤58 years old ( P = 0.023), Karnofsky≥80 scores ( P = 0.026), ascites ≤1 000 ml ( P = 0.041), peritoneal carcinomatosis index (PCI) score <19 ( P = 0.044) and completeness of cytoreduction (CC) score 0-1 ( P = 0.001) had better prognosis. Multivariate analysis showed that CC score 0-1 was independent prognostic factor, the mortality risk of resectable patients with CC score 2-3 was 3.2 times higher than that in patients with CC score 0-1 ( HR = 3.2, 95% CI 1.4-7.6, P = 0.008), and mPFS time was 23.3 months (95% CI 0-50.7 months) for patients with CC score 0-1. Grade Ⅲ-Ⅳ adverse event rate during perioperative period and mortality rate was 4.0% (4/100) and 2.0% (2/100), respectively. Conclusion:CRS+HIPEC could improve the survival of advanced ovarian cancer patients with good safety.
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Objective:s To evaluate the impacts of prior surgical scores(PSS) on the clinical efficacy and perioperative safety of cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) for pseudomyxoma peritonei(PMP).Methods:From the comprehensive PMP database, we collect the cases treated for the first time by CRS+ HIPEC, to form this study cohort. The clinicopathological features, PSS, CRS+ HIPEC details, overall survival(OS), and serious adverse events(SAEs) are systematically analyzed, to study the correlations between PSS and OS or SAEs.Results:335 PMP cases received standardized CRS+ HIPEC in this study. The median OS is 58.2 months for PSS-0 patients, 63.7 months for PSS-1, and 55.4 months for PSS-2/3, with no statistically significant differences in OS among the different PSS groups(χ 2=0.499, P=0.779). Subgroup analysis by pathologic types also found no statistically significant differences among the different PSS groups. Moreover, no significantly statistical differences are observed in overall SAEs(χ 2=0.625, P=0.722), CRS-related SAEs(χ 2=0.267, P=0.901), and non-CRS-related SAEs(χ 2=0.677, P=0.715), among the different PSS groups. Conclusions:PSS does not pose significant impacts on the efficacy and safety of CRS+ HIPEC for PMP patients at experienced treatment center.
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Objective@#To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP.@*Methods@#PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded.@*Results@#The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%.@*Conclusion@#PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.
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Objectives@#To construct a prognosis predictive nomogram for gastric cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.@*Methods@#The clinical data and follow-up results of gastric cancer with peritoneal carcinomatosis patients treated by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at our center from 2005 to 2017 were collected for log-rank test and multivariate COX proportional regression model analysis. A prognostic predictive nomogram was constructed and internally validated.@*Results@#115 patients were included. The median overall survival was 13.1 months, and 1-, 2-, 3-, and 5-year survival rates being 56.5%, 25.3%, 12.6%, and 8.1% respectively. Univariate and the following multivariate analysis identified completeness of cytoreduction, temperature of hyperthermic intraperitoneal chemotherapy and type of adjuvant chemotherapy as independent prognostic factors on overall survival. The nomogram using these three factors showed a concordance index of 0.721 (95% CI: 0.669-0.773). The calibration curves for 1-, 2- and 3 -year survival probability showed a good consistency between actual observation and prediction.@*Conclusions@#The nomogram based on completeness of cytoreduction, temperature of hyperthermic intraperitoneal chemotherapy and type of adjuvant chemotherapy can effectively predict the survival probability for gastric cancer with peritoneal carcinomatosis patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.
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Objectives To construct a prognosis predictive nomogram for gastric cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.Methods The clinical data and follow-up results of gastric cancer with peritoneal carcinomatosis patients treated by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at our center from 2005 to 2017 were collected for log-rank test and multivariate COX proportional regression model analysis.A prognostic predictive nomogram was constructed and internally validated.Results 115 patients were included.The median overall survival was 13.1 months,and 1-,2-,3-,and 5-year survival rates being 56.5％,25.3％,12.6％,and 8.1％ respectively.Univariate and the following multivariate analysis identified completeness of cytoreduction,temperature of hyperthermic intraperitoneal chemotherapy and type of adjuvant chemotherapy as independent prognostic factors on overall survival.The nomogram using these three factors showed a concordance index of 0.721 (95％ CI:0.669-0.773).The calibration curves for 1-,2-and 3-year survival probability showed a good consistency between actual observation and prediction.Conclusions The nomogram based on completeness of cytoreduction,temperature of hyperthermic intraperitoneal chemotherapy and type of adjuvant chemotherapy can effectively predict the survival probability for gastric cancer with peritoneal carcinomatosis patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.
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Objective To evaluate double catheterization of cannula persistent irrigation and negative pressure system to treat gastrointestinocutaneous fistula (GIF) after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for peritoneal cancer.Methods A self-made double catheterization of cannula persistent bathe and negative pressure system was implanted into the site of fistula,to ensure efficient drainage.The patient was treated with anti-sepsis,nutrition support and other conservative measures.Results GIFs occurred in 13 patients.The negative pressure drainage system was successfully implanted into the fistula site to keep an efficient drainage.By this conservative treatment fistula healed in 8 patients after 50 days (range 12 to 84 days).In other three patients fistula output significantly reduced and general conditions greatly improved.The mortality rate was 15％ (2/13).Conclusion The double catheterization of cannula persistent bathe and negative pressure aspiration system is a simple and efficient method to treat GIF.
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Objective:To investigate whether the omental-adipose stromal cells (O-ASCs) exposing to gastric cancer-conditioned medi-um (CM) could be inducted to differentiate into carcinoma-associated fibroblasts (CAFs) and the effect of ERK signaling pathway in the process. Methods: We identified O-ASCs by examining their ability to differentiate osteogenic and adipogenic lineages and through flow cytometry. O-ASCs were co-cultured with MGC803 and SGC7901CM. The expression of CAFs markers (α-SMA, FSP-1, and vimentin) and paracrine factors (VEGFA, TGF-β1, FAP, and SDF-1) were evaluated by RT-PCR and Western blot. In vitro cultures of O-ASCs were divided into three groups:the control, SGC7901-CM, and SGC7901-CM+U0126 groups. Cells were collected after 12 h. West-ern blot was performed to evaluate the expression ofα-SMA, FSP-1, ERK, and p-ERK1/2. Results:The primary cells were O-ASCs. The expression levels of CAFs markers (α-SMA, FSP-1, and vimentin) and O-ASC paracrine factors (VEGFA, TGF-β1, FAP, and SDF-1) clearly in-creased (P0.05), while the ex-pression of p-ERK1/2,α-SMA, and FSP-1 significantly improved (P0.05), while the expression levels of p-ERK1/2,α-SMA, and FSP-1 decreased (P<0.05). Conclusion:O-ASCs participate in the peritoneal metastasis of gastric cancer through differentiation by CAF and paracrine factors. The ERK signaling pathway is important in the differentiation of O-ASCs towards CAFs.
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Objective:To evaluate the efficacy and safety of combined cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with lobaplatin and docetaxel for treatment of synchronous peritoneal carcinomatosis (PC) from gastric cancer. Methods:Fifty patients with synchronous PC from gastric cancer were treated by 52 CRS+HIPEC procedures with 100 mg of lobaplatin and 120 mg of docetaxel in 12000 mL of normal saline at (43 ± 0.5)℃for 60 min. The primary and secondary endpoints were overall survival (OS) and perioperative safety profiles, respectively. Results:At a median follow-up of 22.5 months, the median OS rate was 14.3 (95%CI:7.6-21.0) months, and the 1-, 2-, and 3-year survival rates were 58%, 40%, and 32%, respectively. No perioperative deaths or serious adverse events occurred in 12 cases (23.1%). Multivariate analysis indicated that completeness of cytoreduction, nor-mality of perioperative tumor markers, and adjuvant chemotherapy of more than six cycles were independent predictors for improved survival. Conclusions:CRS+HIPEC with lobaplatin and docetaxel could improve the OS and ensure perioperative safety of patients with synchronous PC from gastric cancer.