Risk Of Peritoneal Metastasis Research Articles

What is the Risk for Peritoneal Metastases and Survival Afterwards in T4 Colon Cancers?

Patients with T4 colon adenocarcinomas have an increased risk of peritoneal metastases (PM) but the histopathologic risk factors for its development are not well-described. The purpose of this study was to determine factors associated with PM, time to recurrence, and survival after recurrence among patients with T4 colon cancer. Patients with pathologic T4 colon cancer who underwent curative resection from 2005 to 2017 were identified from a prospectively maintained institutional database and classified by recurrence pattern: (a) none - 68.8%; (b) peritoneal only - 7.9%; (c) peritoneal and extraperitoneal - 9.9%; and (d) extraperitoneal only - 13.2%. Associations between PM development and patient, primary tumor, and treatment factors were assessed. Overall, 151 patients were analyzed, with a median follow-up of 66.2 months; 27 patients (18%) developed PM (Groups B and C) and 20 (13%) patients recurred at non-peritoneal sites only (Group D). Median time to developing metastases was shorter for Groups B and C compared with Group D (B and C: 13.7 months; D: 46.7 months; p=0.022). Tumor deposits (TDs) and nodal stage were associated with PM (p<0.05), and TDs (p=0.048) and LVI (p=0.015) were associated with additional extraperitoneal recurrence. Eleven (41%) patients with PM underwent salvage surgery, and median survival after recurrence was associated with the ability to undergo cytoreduction (risk ratio0.20, confidence interval 0.06-0.70). PM risk after resection of T4 colon cancer is independently associated with factors related to lymphatic spread, such as N stage and TDs. Well-selected patients can undergo cytoreduction with long-term survival. These findings support frequent postoperative surveillance and aggressive early intervention, including cytoreduction.

ASO Visual Abstract: What is the Risk for Peritoneal Metastases and Survival Afterwards in T4 Colon Cancers?

ASO Visual Abstract: What is the Risk for Peritoneal Metastases and Survival Afterwards in T4 Colon Cancers?

184P Development and external validation of a nomogram to predict recurrence-free survival after R0 resection for stage II/III gastric adenocarcinoma: An international multicenter study

The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC. Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n=1240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n=306) and a US cohort (n=111), respectively. The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram’s predictive performance was confirmed in both the internal and external validation cohorts. A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention.

Development and External Validation of a Nomogram to Predict Recurrence-Free Survival After R0 Resection for Stage II/III Gastric Cancer: An International Multicenter Study.

Background: The benefit of adjuvant chemotherapy varies widely among patients with stage II/III gastric cancer (GC), and tools predicting outcomes for this patient subset are lacking. We aimed to develop and validate a nomogram to predict recurrence-free survival (RFS) and the benefits of adjuvant chemotherapy after radical resection in patients with stage II/III GC.Methods: Data on patients with stage II/III GC who underwent R0 resection from January 2010 to August 2014 at Fujian Medical University Union Hospital (FMUUH) (n = 1,240; training cohort) were analyzed by Cox regression to identify independent prognostic factors for RFS. A nomogram including these factors was internally and externally validated in FMUUH (n = 306) and a US cohort (n = 111), respectively.Results: The multivariable analysis identified age, differentiation, tumor size, number of examined lymph nodes, pT stage, pN stage, and adjuvant chemotherapy as associated with RFS. A nomogram including the above 7 factors was significantly more accurate in predicting RFS compared with the 8th AJCC-TNM staging system for patients in the training cohort. The risk of peritoneal metastasis was higher and survival after recurrence was significantly worse among patients calculated by the nomogram to be at high risk than those at low risk. The nomogram's predictive performance was confirmed in both the internal and external validation cohorts.Conclusion: A novel nomogram is available as a web-based tool and accurately predicts long-term RFS for GC after radical resection. The tool can also be used to determine the benefit of adjuvant chemotherapy by comparing scores with and without this intervention.

Early laparoscopic radiofrequency ablation for spontaneous rupture of hepatocellular carcinoma

Objective To evaluate the efficacy and clinical outcomes of early laparoscopic radiofrequency ablation(RFA) forspontaneously ruptured hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on 12 patients with spontaneously ruptured HCC treated by laparoscopic RFA from April 2005 to June 2018 in the West Campus of Beijing Chao-yang Hospital, Capital Medical University. The successful rate, safety, peritoneal recurrence rate, complete ablation rate and survival rate of RFA were respectively analyzed. Results The median size of the 12 HCC cases was 5.85 cm (4.0-10.1 cm) in the maximal dimension. Procedures of laparoscopic RFA ablation were performed successfully for all patients. Complete ablation was achieved in 58.3%patients (7/12). Five patients with incompletely ablated tumors received repeated RF ablation to achieve completeablation. Four patients (33.3%) developed minor complications(Dindo-Clavien gradeⅠ). The mean follow-up of 36.8 months, 4 patients (33.3%) were alive and 8 (66.7%) died. Of the 12 patients, the 1- and 3-year survival rates were 90.0% and 60.0%, respectively.No patient had peritoneal recurrence. Conclusion Early laparoscopic RFA therapy is an minimally invasive, safety and effective treatment measure for spontaneouslyruptured HCC in selected patients, which presents an advantage of achieving simultaneous hemostasis, tumorelimination, and rinsing of peritoneal cavity to minimize the risk of peritoneal metastasis. Key words: Carcinoma, hepatocellular; Laparoscopes; Hemorrhage; Radiofrequency ablation

Association of SMAD4 gene mutation with incidence of peritoneal involvement in unresectable metastatic colorectal cancer.

772 Background: Dorsophilia protein, mothers against decapentaplegic homolog 4 (SMAD4) is involved in TGF- β and Bone Morphogenic Protein (BMP) signaling pathways. Dysregulation in these signaling pathways has been associated with carcinogenesis and poor prognosis in colorectal cancer (CRC). Recent evidence suggests that SMAD4 mutations in CRC may be associated ovarian metastasis, however, the link to peritoneal involvement has not been established. Methods: Patients with next generation sequencing of 50 cancer related genes and unresectable metastatic CRC were identified from a prospectively maintained medical oncology department database. Clinicopathological variables, metastatic sites, and genetic mutations were compared between patients with SMAD4 mutant and SMAD4 wild type patients. Multivariable analysis was then performed to evaluate for factors associated with peritoneal involvement. Results: 324 patients with unresectable metastatic CRC were identified and of these 36 (11%) were SMAD4 mutants. Clinicopathologic variables and additional cancer related gene mutations were similar between SMAD4 mutant and wild type patients. Patients with SMAD4 mutations were more likely to present with peritoneal metastatic disease (50% vs. 24%, p = 0.002) and less likely to present with hepatic metastasis (39% vs 59%, p = 0.021). Metastatic rates to the lungs, distant lymph nodes, and multiple metastatic sites at presentation were similar between the two groups. In patients with metachronous metastatic disease (n = 131), SMAD4 mutation patients demonstrated a trend towards shorter interval to metastatic recurrence (12 vs. 23 months, p = 0.059). During a median follow up of 26 months, SMAD4 mutation patients were more likely to develop peritoneal involvement at either presentation or in progression of disease (58 vs. 35%, p = 0.010). Multivariable analysis showed that compared to other mutations, only the SMAD4 mutation was associated with a higher risk of peritoneal metastasis (OR 2.5, 195% CI 1.2-5.6, p = 0.025). Conclusions: In patients with unresectable metastatic colorectal cancer, SMAD4 mutation is independently associated with peritoneal metastasis.

Establishment of nomogram model to predict peritoneal metastasis in colon cancer patients without distant metastasis by preoperative imaging examination

To establish a nomogram model to predict the peritoneal metastasis in colon cancer patients without distant metastasis by preoperative imaging examination. Clinicopathological data of colon cancer patients without distant metastasis by preoperative imaging examination who underwent surgery in our department between January 2000 and December 2014 were retrospectively analyzed. Predictors of peritoneal carcinomatosis were analyzed by univariate and Logistic multivariate analyses. Base on the independent predictors by multivariable analysis results, a nomogram model was formulated with further use of R software. The total score was calculated by the addition of each predictor score, indicating the corresponding risk of peritoneal metastasis. The score was greater in the nomogram, and the risk was higher in peritoneal implantation metastasis. A receiver operating characteristic(ROC) curve was then constructed to evaluate the predictive abilities of the various preoperative factors and nomogram. A total of 1 417 patients were defined as above and enrolled in the study. The median age was (60.5±13.3) years, 835 cases (58.9%) were male, and 132 cases (9.3%, 132/1417) were diagnosed with synchronous peritoneal carcinomatosis during operation. Univariate analysis showed that peritoneal metastasis was associated with age, incidence of abdominal pain, incidence of mucous bloody stool, CEA level, traversible rate, tumor diameter, ratio of infiltrating type cancer, differentiation, histological type, cT staging and cN staging (all P<0.05). Logistic multivariate analysis revealed that younger age (OR:0.974, 95%CI: 0.958 to 0.990, P=0.001), later clinical T stage (OR: 2.949, 95%CI: 1.588 to 5.476, P=0.001), lesion not traversible(OR: 0.519, 95%CI: 0.314 to 0.858, P=0.011), infiltrative gross type (OR: 1.812, 95%CI: 1.099 to 2.987, P=0.020), larger tumor (OR: 1.044, 95%CI: 0.998 to 1.093, P=0.061), higher preoperative serum CEA level(OR:1.004,95%CI: 1.001 to 1.007, P=0.007) and histopathologic type of mucinous or signet ring cell adenocarcinoma (OR:1.642, 95%CI: 1.009 to 2.673, P=0.046) were independent risk factors. The nomogram model was further established based on above 7 independent risk factors, whose total score was 350 and area under the ROC curve was 0.753(P=0.000). The nomogram model can be helpful to screen the colon cancer patients with high risk of peritoneal metastasis and to avoid unnecessary laparotomy for colon cancer patients without distant metastasis by preoperative imaging examination.

Risk of peritoneal metastases in patients who had negative peritoneal staging and received therapy for localized gastric adenocarcinoma.

Positive peritoneal cytology (+PCyt) or gross carcinomatosis (GPC) carries a poor prognosis. Laparoscopic staging to detect +PCyt/GPC is recommended for all ≥T1b gastric adenocarcinoma (GAC). The natural history of patients with GAC who have baseline -PCyt and then undergo multimodality therapy is not well documented, particularly for the risk of subsequent GPC. We identified 238 GAC patients with baseline -PCyt who were followed for the development of peritoneal carcinomatosis (PC). Standard statistical methods were employed. Of 238 patients, 192 had attempted surgery after preoperative therapy. Of these, 13 patients (6.8%) had GPC and one had liver metastases, thus surgery was aborted. We followed 164 patients who had an R0 resection. The median follow-up duration was 3.4 (range, 0.6-18) years. The rate of PC was 13.4%, (22/164 patients) and the median time to PC was 15.6 months. Female gender was associated with PC on multivariate analysis. The 5-year OS rate for patients without subsequent PC was 75%. Conclusion Even with baseline -Cyt, ∼25% of patients develop PC following multimodality therapy. Patients who do not develop PC have an excellent OS rate. Further research is warranted to detect PC at baseline by the use of biomarkers.

Update on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer.

The prevention of a disease process has always been superior to the treatment of the same disease throughout the history of medicine and surgery. Local recurrence and peritoneal metastases occur in approximately 8% of colon cancer patients and 25% of rectal cancer patients and should be prevented. Strategies to prevent colon or rectal cancer local recurrence and peritoneal metastases include cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These strategies can be used at the time of primary colon or rectal cancer resection if the HIPEC is available. At institutions where HIPEC is not available with the treatment of primary malignancy, a proactive second-look surgery is recommended. Several phase II studies strongly support the proactive approach. If peritoneal metastases were treated along with the primary colon resection, 5-year survival was seen and these results were superior to the results of treatment after peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look has been shown to be effective in two published manuscripts. Unpublished data from MedStar Washington Cancer Institute also produced favorable date. Rectal cancer with peritoneal metastases may not be so effectively treated. There are both credits and debits of this proactive approach. Selection factors should be reviewed by the multidisciplinary team for individualized management of patients with or at high risk for peritoneal metastases.

Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases.

A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28%) (p < 0.03). Patients in the proactive group also survived longer than control patients (median overall survival 59.5 vs 52 months). Despite similar morbidity, Kaplan-Meier survival curves disclosed significantly longer disease-free and overall survival in the proactive than in the control group (p < 0.05 and <0.04). In patients with advanced colon cancer at risk for peritoneal recurrence, the proactive surgical approach plus HIPEC seems to achieve good locoregional control preventing peritoneal spread thus improving outcome without increasing morbidity. These advantages merit investigation in a multicentric randomized trial.