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ObjectiveTo construct a human ovarian cancer cell line SKOV3 （SK-Luc-EGFP） stably co-expressing luciferase （Luc） and enhanced green fluorescent protein （EGFP） and to explore its application in ovarian cancer research both in vitro and in vivo. MethodsThe recombinant plasmid pCDH-Luc-T2A-EGFP-Puro was constructed by introducing a Luc-T2A-EGFP fusion gene fragment amplified by Overlap PCR into plasmid vector. The three-plasmid lentivirus packaging system was transfected into HEK 293T cells and the viral supernatant was harvested to infect SKOV3 cells. SK-Luc-EGFP cell line with the highest fluorescence intensity of EGFP was obtained by puromycin selection and flow cytometry assessment， and the Luc expression of the cell line was subsequently validated by in vitro bioluminescent assay. SK-Luc-EGFP cells were further explored for the following applications： distinguishing SK-Luc-EGFP cells from non-tumor cells in ascites by flow cytometry and confocal microscopy； visualizing adhesion of SK-Luc-EGFP cells to mesothelial cells or omentum by fluorescence microscopy； monitoring process of SK-Luc-EGFP tumorigenesis by in vivo bioluminescence imaging. ResultsA recombinant lentiviral expression plasmid pCDH-Luc-T2A-EGFP-Puro was constructed and packaged into lentiviral particles that were then transfected into SKOV3 cells to generate SK-Luc-EGFP cell line. The purity of SK-Luc-EGFP cells based on EGFP expression was 100% as validated by fluorescence microscopy and flow cytometry； SK-Luc-EGFP cells could be visually distinguished from non-tumor cells in ascitic fluid by flow cytometry and confocal imaging. Moreover， Luc expression in SK-Luc-EGFP cells was verified by in vitro bioluminescence assay， and a linear relationship with a correlation coefficient of 0.997 9 was found between cell number and the bioluminescent signal. Adhesion of SK-Luc-EGFP cells to mesothelial cells was directly observed by fluorescence imaging in in vitro adhesion assay； peritoneal adhesion of SK-Luc-EGFP cells to omentum was also observed after intraperitoneal （i.p.） injection of SK-Luc-EGFP cells in nude mice； in the peritoneal metastasis mouse model established by i.p. injection of SK-Luc-EGFP cells， monitoring of tumorigenesis process was achieved by in vivo bioluminescence imaging. ConclusionSK-Luc-EGFP cell line is a useful tool for investigating ovarian cancer in vitro and in vivo.
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Objective:To verify the transforming therapeutic efficacy of apatinib combined with oxaliplatin + tegiol (SOX regimen) in advanced gastric cancer with peritoneal metastasis.Methods:Using the method of descriptive case series study, the data of gastric cancer patients with peritoneal metastasis treated in Zhejiang Provincial People′s Hospital and Shulan (Hangzhou) Hospital from March 2016 to August 2021 were collected and treated with apatinib combined with SOX regimen. Oxaliplatin 130 mg/m 2, intravenous drip, day 1; Apatinib mesylate tablets 500 mg/d, oral, once a day, 1-21 days; Teggio: calculate the dosage according to the body surface area (<1.25 m 2, 40 mg; 1.25-1.50 m 2, 50 mg; >1.50 m 2, 60 mg). Take it orally for 1-14 days, twice a day. From the first day of chemotherapy, a cycle of 3 weeks. The short-term efficacy was evaluated every 2 cycles. After that, the multidisciplinary treatment team will decide whether the conversion operation can be accepted. When the requirements of surgical resection were met, the operation will be carried out after 1 cycle of drug withdrawal. Results:The median survival time (MST) of 23 patients was 14.1 months (95% CI: 12.3-16.4); The median overall survival (OS) after transformation therapy was 19.1 months (95% CI: 15.5-22.8). After transformation therapy, 14 cases of partial remission (PR), 3 cases of stable disease (SD) and 6 cases of progression disease (PD) in 23 patients, and the objective remission rate (ORR) was 73.9%(17/23). 12(52.2%) patients underwent surgery after transformation therapy. The 1-year OS of 12 patients was (17.0±1.5)months; Among them, 5 cases underwent R0 resection, and the R0 resection rate was 5/12. Conclusions:Transformation treatment with apatinib combined with oxaliplatin + tegio (SOX regimen) in advanced gastric cancer can achieve a high R0 resection rate with better conversion effect.
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Objective:To investigate the efficacy of CT imaging features in evaluating occult peritoneal metastasis (OPM) of diffuse infiltrating gastric cancer (Borrmann Type Ⅳ).Methods:Totally 101 patients with locally advanced Borrmann type Ⅳ gastric cancer were retrospectively collected who were admitted to Peking University Cancer Hospital from March 2014 to March 2021. The patients were divided into OPM group (53 cases) and the non-OPM group (48 cases) according to the results of preoperative CT and laparoscopic exploration/peritoneal cytology examination. The pathological examination results were recorded, including the degree of histological differentiation and Lauren classification. The evaluation indicators included the tumor center position, the number of tumor-occupied portions, involved orientation, mucosal broadband sign, stratified enhancement, serosa invasion, increased density of peripheral fat tissue, and enlarged lymph nodes. The maximum thickness of the primary tumor, average CT value of the primary tumor (arterial phase, venous phase, and delayed phase), difference between venous phase and arterial phase, difference between delayed phase and venous phase, and pattern of the enhanced curve were recorded. The Mann-Whitney U or Chi-square test was used to compare the differences of pathological and CT features between two groups. The multivariate logistic regression was used to screen independent predictors and establish a nomogram. The receiver operating characteristic curve was used to evaluate the performance of the nomogram in predicting OPM, and the Hosmer-Lemeshow test was used to test the model′s goodness of fit. Results:There was statistical significance in the seven indicators between the OPM and non-OPM groups, including tumor-occupied portions of stomach, mucosal broadband sign, stratified enhancement, serosa invasion, increased density of peripheral fat tissue, the enhanced curve pattern and the degree of histological differentiation ( P<0.05). Among them, the degree of histological differentiation (OR=0.19, P=0.033), stratified enhancement (OR=7.02, P=0.005) and serosa invasion (OR=14.27, P<0.001) were independent predictors of OPM. The nomogram was established based on the three significant features. The area under the curve for predicting OPM was 0.826 (95%CI 0.745-0.908), the sensitivity was 0.566 and the specificity was 0.938. The Hosmer-Lemeshow test showed a good agreement between the OPM risk predicted by the nomogram and the actual risk ( P=0.525). Conclusions:The CT features of Borrmann type Ⅳgastric cancer complicated with OPM have specific characteristics. The diagnosis model based on the degree of histological differentiation, stratified enhancement, and serosa invasion had high efficacy in evaluating OPM.
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Objective:To investigate the predictive value of visceral adipose tissue (VAT) in occult peritoneal metastasis (OPM) of gastric cancer.Methods:A total of 93 patients with gastric cancer admitted to the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2021 were retrospectively collected. None of the patients had typical peritoneal metastasis on CT. Patients were divided into OPM group (31 cases) and non-OPM group (62 cases) according to laparoscopic exploration. The clinical, pathological and CT features were recorded. The parameters related to adipose tissue (VAT and subcutaneous adipose tissue) within the range of 15 mm and 25 mm below the largest layer of gastric cancer lesions in preoperative CT images were measured, including the volume, average CT attenuation and standard deviation. The independent-sample t test, Wilcoxon rank-sum test, χ 2 test or Fisher′s exact probability were used to compare the clinical, pathological and CT imaging parameters between OPM and non-OPM groups. Multivariate logistic regression analysis was used to explore the independent risk factors for OPM of gastric cancer and establish a combined model. The receiver operating characteristic curve was used to evaluate the efficacy of each indicator and the combined model in predicting OPM of gastric cancer. Results:There were statistically significant differences in age, pathological type, CA125, ascites, cT stage, the thickest diameter of lesion, average CT attenuation of 15 mm VAT and 25 mm VAT between the OPM group and the non-OPM group ( P<0.05). Multivariate analysis showed that ascites, cT stage and average CT attenuation of 25 mm VAT were independent risk factors for OPM of gastric cancer, with the OR (95%CI) of 4.940 (1.287-18.967), 4.284 (1.270-14.455), and 1.149 (1.013-1.303), respectively. A combined model was established. The area under the curve (AUC) of ascites, cT stage, average CT attenuation of 25 mm VAT, average CT attenuation of 15 mm VAT and combined model were 0.685, 0.718, 0.703, 0.674 and 0.813, respectively. There were statistically significant differences in AUC between the combined model and each four single indicators above ( Z=2.98, 2.63, 2.09, 2.54, P=0.003, 0.009, 0.037, 0.011). Conclusions:The ascites, cT stage and average CT attenuation of 25 mm VAT are independent risk factors for OPM in gastric cancer. The combined model based on the above three indicators has the best performance in predicting OPM in gastric cancer.
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Ovarian cancer has the highest mortality among the three major gynecological malignancies. Peritoneal metastasis, intestinal obstruction and then death is the main outcome pattern of advanced ovarian cancer. Traditional Chinese medicine maintenance treatment of advanced ovarian cancer is effective, but the theoretical basis needs to be further improved. Under the guidance of the membranous Sanjiao theory and combined with clinical experience, this paper traces the origin, focuses the location of membranous Sanjiao of ovarian cancer peritoneal metastasis and the role of membranous Sanjiao dysfunction in the occurrence and metastasis of ovarian cancer. Besides, the paper puts forward that the main strategies for the maintenance treatment of traditional Chinese medicine on ovarian cancer are ordering the Qi movement of Sanjiao, regulating and harmonizing Qi and blood, and clearing away the latent toxin. From the perspective of membranous Sanjiao theory, the theory enriches the traditional Chinese medicine theory of ovarian cancer and provides new ideas for the treatment of ovarian cancer.
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Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Adenocarcinoma, Mucinous/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/surgery , Colorectal Neoplasms/pathology , Combined Modality Therapy , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Peritoneal Neoplasms/secondary , Retrospective Studies , Survival RateABSTRACT
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.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/drug therapy , Peritoneum , Prognosis , Quality of Life , Survival RateABSTRACT
Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Cancer, Regional Perfusion , Colorectal Neoplasms/therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/drug therapy , Prognosis , Randomized Controlled Trials as Topic , Survival RateABSTRACT
Objective: To investigate the safety and short-term efficacy of apatinib combined with oxaliplatin and S-1 in the conversion treatment for gastric cancer with different types of peritoneal metastasis. Methods: A prospective study "one arm exploratory clinical study of conversion therapy of apatinib with S-1 and oxaliplatin in the treatment of advanced gastric cancer" (clinical registration ChiCTR-ONC-17010430) from medical record database was retrospectively analyzed. Patients aged 18-70 years with gastric cancer peritoneal metastasis confirmed by histology and laparoscopic exploration, and had not receive radiotherapy, chemotherapy, targeted therapy or immunotherapy before were enrolled. Before operation, the patients received 6 cycles of S-1 (80-120 mg/d, d1-d14) and oxaliplatin (130 mg/m(2), d1), and 5 cycles of apatinib (500 mg/d, d1-d21) conversion regimen. Three weeks after chemotherapy, whether the operation was performed or not depending on re-evaluation and patient preference. The main outcome were adverse reactions, and the secondary outcome were objective remission rate (ORR), disease control rate (DCR), and overall survival (OS) rate. The follow-up period was up to May 2020. Results: A total of 27 patients with gastric cancer peritoneal metastasis were enrolled in this study. There were 13 males and 14 females, with a median age of 58 (30-68) years old. There were 9 cases of P1a, 5 cases of P1b, and 13 cases of P1c. There were 14 cases with 1-5 scores of PCI (peritoneal cancer index), and 13 cases with 6 scores or above. The incidence of adverse reactions was 100%. The most common adverse reactions were hematological events including leucopenia (70.4%, 19/27) and granulocytopenia (74.1%, 20/27). Non-hematological adverse events included fatigue (51.9%, 14/27) and oral mucositis (37.0%, 10/27). One patient was withdrawn due to grade 4 thrombocytopenia. Among 26 patients with feasible efficacy evaluation, 18 (69.2%) achieved partial remission, 3 (11.5%) achieved stable disease, and 5 (19.2%) disease progression. The objective remission rate was 69.2% (18/26) and the disease control rate was 80.8% (21/26). Fourteen patients underwent surgery, including 6 patients undergoing R0 resection with the R0 resection rate of 42.9% (6/14). The postoperative pathological response rate was 64.3% (9/14). The follow-up time was 12-40 months, and the follow-up rate was 100%. The 1-year OS rate was 65.2% and the survival time was (14.0±1.7) months. The 1-year OS rates of P1a/P1b group and P1c group were 81.8% and 42.0% respectively, whose difference was statistically significant (P=0.041). The 1-year OS rates of PCI 1-5 group and PCI ≥6 group were 67.3% and 38.5% respectively, whose difference was statistically significant (P=0.022). Conclusion: In the conversion treatment of gastric cancer peritoneal metastasis, the safety of apatinib combined with oxaliplatin and S-1 is acceptable, and this regimen shows a good short-term survival efficacy in patients with P1a/P1b and PCI of 1-5.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Oxaliplatin , Percutaneous Coronary Intervention , Peritoneal Neoplasms/drug therapy , Prospective Studies , Pyridines , Retrospective Studies , Stomach Neoplasms/drug therapyABSTRACT
Peritoneal metastasis of gastrointestinal cancer is an independent factor that seriously affects the prognosis of patients. The "seed-soil" theory is considered to be the main theory to explain peritoneal metastasis. Because of the small size of peritoneal metastatic nodules at the initial stage, early diagnosis is particularly difficult, therefore, the risk assessment of peritoneal metastasis is very important. Recently, the diagnosis methods have gradually developed from clinicopathological factors to cytology and molecular level. In addition, the integrated assessment of multiple groups including radiomics further enriches the accurate diagnosis of peritoneal metastasis. Peritoneal metastasis is a big challenge in the treatment of gastrointestinal cancer which may also lead to refractory malignant ascites, intestinal obstruction, cachexia and other related complications. At present, the treatment is based on systemic chemotherapy. The combination of surgery, intraperitoneal chemotherapy and HIPEC is an effective treatment for peritoneal metastasis of gastrointestinal cancer. How to enrich peritoneal metastasis patients with potential benefits, how to determine the timing of conversion surgery, how to further optimize the existing treatment plan, especially how to formulate treatment plan for patients after conversion surgery, call for improved study design and prospective randomized controlled trials. The goal of continuous efforts is to effectively prolong the survival of gastrointestinal cancer trials patients with peritoneal metastasis.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Combined Modality Therapy , Gastrointestinal Neoplasms/drug therapy , Hyperthermia, Induced , Peritoneal Neoplasms/drug therapy , Peritoneum , Prospective Studies , Stomach Neoplasms/therapyABSTRACT
Peritoneal metastasis is the most common distant metastasis of gastric cancer. As an end-stage event of gastric cancer, patients with peritoneal metastasis often have lost the chance of radical resection, and even after palliative surgical resection, the long-term outcomes are still not satisfactory. In recent years, with the application and promotion of laparoscopic technology, neoadjuvant intraperitoneal and systemic chemotherapy, hyperthermic intraperitoneal chemotherapy and cytoreductive surgery, through perioperative comprehensive treatment strategies by multidisciplinary team, the quality of life and survival of patients with peritoneal metastasis have been significantly improved. Some patients with gastric cancer peritoneal metastasis diagnosed by laparoscopy even get the opportunity to have radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy after neoadjuvant intraperitoneal and systemic chemotherapy. Taking into account the progress in the treatment of gastric cancer peritoneal metastasis in recent years, this article intends to combine current clinical evidence and to discuss the key issues in the course of clinical diagnosis and treatment of gastric cancer peritoneal implantation and metastasis, including the imaging diagnosis of peritoneal metastasis, laparoscopic examination, evaluation of peritoneal metastasis and comprehensive treatment plan.
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Humans , Antineoplastic Combined Chemotherapy Protocols , Combined Modality Therapy , Cytoreduction Surgical Procedures , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Peritoneum , Quality of Life , Stomach Neoplasms/therapyABSTRACT
Gastrointestinal cancer peritoneal metastasis(GICPM) is one of the biggest challenges of clinical treatment. The ultimate solution to the problem requires the clinicians to accurately understand cytologic and molecular pathological mechanisms behind GICPM, and apply such knowledge in the clinical decision-making process for diagnosis and treatment of individual patient, so as to realize "prevention" and "treatment" proactively. The core cytopathological mechanisms behind GICPM, which are closely related to clinical treatment decisions, are as follows: (1) free cancer cells or clusters in peritoneal cavity colonize the peritoneum, resulting in irreversible pathological damage to peritoneal mesothelial cells; (2) the colonized cancer cells further invade the specific structure of the peritoneal milky spots and initiate an accelerated invasive growth process; (3) the process of peritoneal interstitial fibrosis aggravates the structural destruction of the peritoneum; (4) the interaction between cancer cells and immune cells in the milk spots forms a permissive immune microenvironment that promotes the growth of peritoneal metastatic cancer. These four core cytopathological mechanisms are mutually causal and promote each other, forming a vicious circle of GICPM development. As long as clinicians accurately understand these four points, it is possible to grasp the opportunity of clinical diagnosis and treatment, change reactive and passive treatment into preventive and proactive treatment, and improve the clinical diagnosis and treatment landscape of GICPM.
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Humans , Intestinal Neoplasms , Peritoneal Cavity , Peritoneal Neoplasms , Peritoneum , Tumor MicroenvironmentABSTRACT
Background: Colorectal cancer, a formidable health problem worldwide has upto 8% synchronous peritoneal carcinomatosis. As only diagnostic laparoscopy can identify them, in countries with economic burden, selection of patients for laparoscopy is ideal. Our aim is to evaluate whether the baseline Carcinoembryonic antigen (CEA) is a good selection tool.Methods: A retrospective study of 125 patients, who were diagnosed to have colorectal malignancy (any stage) and underwent elective surgery at our institution from 2012 till 2019 were included. The baseline serum CEA was compared with the intraoperative findings. The threshold levels of serum CEA compared were 6.5 and 100 ng/dl. The sensitivity, specificity, positive predictive value and negative predictive value for both thresholds were compared in 3 categories of patients, namely peritoneal metastasis (9 cases), metastasis to other organs (36 cases) and cases with no metastasis either in peritoneum or other organs (85 cases). The results were analysed using SPSS software.Results: The mean age was 65, sex ratio (male:female) was 72:53. The sensitivity, specificity, positive predictive value, negative predictive value (NPV) for CEA threshold of 6.5 ng/dl was 44.44%, 60.34%, 8% and 93.33% for category 1. For CEA threshold of 100 ng/dl, it was 33.33%, 97.41%, 50% and 94.95% for category 1. NPV was 96.55% for category 3 (the highest value).Conclusions: If the baseline CEA levels are less than 100 ng/dl, 96.55% of cases will not require a diagnostic laparoscopy. This hopefully will cut down the cost of unnecessary diagnostic laparoscopies, and reduce the morbidity of unnecessary laparotomies.
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PURPOSE: The objective of the present retrospective analysis was to describe the experience of intraperitoneal (IP) paclitaxel and systemic chemotherapy in patients with peritoneal metastasis (PM) of advanced gastric cancer (AGC) in a multicenter setting in Korea.MATERIALS AND METHODS: The medical records of patients with AGC, who were diagnosed with PM between January 2015 and December 2018, were reviewed. IP catheter was placed in the pouch of Douglas and was used for the administration of IP paclitaxel chemotherapy.RESULTS: We reviewed the clinical outcomes of IP paclitaxel and systemic chemotherapy administration in 82 patients at six institutions in Korea. Mean number of IP chemotherapy cycles was 6.6. The mean peritoneal cancer index (PCI) was 21.9. Postoperative complications related to IP catheter and port were observed in 15 patients. The overall median survival was 20.0 months. A significant difference was observed in the survival rate according to the ascites grade (grade I and II, 24.1 months; grade III and IV, 15.3 months; P=0.014) and PCI grade (grade I, 25.6 months; grade II and III, 16.3 months; P=0.023).CONCLUSIONS: The feasibility of IP paclitaxel and systemic chemotherapy administration was demonstrated in this experience-based retrospective analysis suggesting that the procedure is beneficial in patients with PM of AGC.
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Objective: To investigate the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) for gallbladder cancer with peritoneal metastasis. Methods: Data of 84 patients, who were admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from January 2015 to January 2018, were retrospectively analyzed. Of the total patients, 31 received HIPEC combined with cytoreductive surgery (CRS) plus postoperative systemic chemotherapy one month after surgery as the study group (Group A), and the other 53 underwent CRS plus postoperative systemic chemotherapy one momth after surgery as the control group (Group B). The clinical effects and adverse reactions in the two groups were observed and compared. Results: The median survival time in the Group A was (21.72±2.96) months, significantly longer than that of (14.93±2.09) months in Group B (P0.05). Conclusions: HIPEC has significant clinical efficacy for gallbladder cancer with peritoneal metastasis. HIPEC can prolong the survival time and have less side effects.
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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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Peritoneum is the third common metastatic site of colorectal cancer (CRC) following liver and lung. CRC peritoneal metastasis (PM) has been reckoned as an advanced disease with dismal prognosis. With the development of modern chemotherapeutic modalities, the prognosis of patients with metastatic CRC has been dramatically improved, yet patients with CRC PM achieved few survival benefits. It is the emergence and combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy that prolong the survival of PM cases. What's more, novel treatments, pressurized intraperitoneal aerosol chemotherapy, and intraperitoneal MOC31PE immunotoxin treatment, for instance, have been under investigation and preliminary results are promising. We aim to comprehensively review the literature focusing on the clinical treatment of PM.
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With the prevalence of diagnostic laparoscopy, the concept of conversion therapy in unresectable gastric cancer, as well as the technical application of port implantation and hyperthermic intraperitoneal chemotherapy, new progress has been made in the area of gastric cancer peritoneal metastasis. However, the prognosis for peritoneal metastasis of gastric cancer remains extremely poor, and surgical treatment still lacks high-level evidence. Surgeons should pay attention to standardized diagnosis and evaluation during medical practice, and should conduct multidisciplinary discussions on important issues, such as patient screening, surgical indications, and postoperative chemotherapy. The progress of drug therapy is still the key to improve the prognosis of gastric cancer peritoneal metastasis in the future.
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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.
ABSTRACT
The presence of ovarian or peritoneal metastasis in early-stage cervical malignancy is a rare entity. It often poses a diagnostic challenge whether it is a synchronous primary tumor or a metastatic lesion. A 63-year-old postmenopausal woman presented with Stage 1B1 carcinoma cervix with ascites, and a 5.8 cm × 4.2 cm × 3.5 cm left solid adnexal mass. She underwent Type III radical hysterectomy, excision of peritoneal mass, with bilateral pelvic and paraaortic lymphadenectomy and infracolic omentectomy. On histopathology, cervix showed features of adenocarcinoma, and the peritoneal mass revealed similar histomorphology as cervical growth with metastatic tumor deposits in omentum. Immunohistochemistry (IHC) was utilized to determine the origin of mass. The early stage disease and histology may not always predict the distant metastasis. Therefore, a thorough pretreatment evaluation, meticulous intraoperative assessment, and IHC are mandatory for optimum management and prognostication