Peritoneal Carcinomatosis Index Research Articles

Simultaneous Surgical Approach with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Concurrent Peritoneal and Liver Metastases of Colon Cancer Origin.

Background: Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions: Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

Predicting Severe Complications from Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Data-Driven, Machine Learning Approach to Augment Clinical Judgment.

CRS-HIPEC provides oncologic benefit in well-selected patients with peritoneal carcinomatosis; however, it is a morbid procedure. Decision tools for preoperative patient selection are limited. We developed a risk score to predict severity of 90day complications for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Adults who underwent CRS-HIPEC at the University of Pittsburgh Medical Center (March 2001-April 2020) were analyzed as part of this study. Primary endpoint was severe complications within 90days following CRS-HIPEC, defined using Comprehensive Complication Index (CCI) scores as a dichotomous (determined using restricted cubic splines) and continuous variable. Data were divided into training and test sets. Several machine learning and traditional algorithms were considered. For the 1959 CRS-HIPEC procedures included, CCI ranged from 0 to 100 (median 32.0). Adjusted restricted cubic splines model defined severe complications as CCI > 61. A minimum of 20 variables achieved optimal performance of any of the models. Linear regression achieved the highest area under the receiving operator characteristic curve (AUC, 0.74) and outperformed the NSQIP Surgical Risk calculator (AUC 0.80 vs. 0.66). Factors most positively associated with severe complications included peritoneal carcinomatosis index score, symptomatic status, and undergoing pancreatectomy, while American Society of Anesthesiologists 2 class, appendiceal diagnosis, and preoperative albumin were most negatively associated with severe complications. This study refines our ability to predict severe complications within 90days of discharge from a hospitalization in which CRS-HIPEC was performed. This advancement is timely and relevant given the growing interest in this procedure and may have implications for patient selection, patient and referring provider comfort, and survival.

Syntaxin 6 Enhances the Progression of Epithelial Ovarian Cancer by Promoting Cancer Cell Proliferation.

The aim of this study is to evaluate the expression of syntaxin 6 (STX6) in epithelial ovarian cancer (EOC) and assess the effects of STX6 on the prognosis of patient. Using information from the Kaplan-Meier Plotter database, the effects of STX6 expression on overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients were examined. The clinical information of 147 patients with epithelial ovarian cancer was evaluated, and immunohistochemical staining was used to identify STX6 expression in postoperative tumor specimens, and the affection of STX6 expression on patient prognosis was assessed. In addition, the expression of STX6 in tumor tissue, peritoneal metastases (PM) derived from 13 patients with epithelial ovarian cancer and 6 normal ovarian specimens was detected by PCR and Western blot. In order to investigate how STX6 affects the proliferation of tumor cells, STX6 was also over expressed and knock down in ovarian cancer cell lines. Then colony formation assay was used to explore the effect of STX6 regulating on cell proliferation. Kaplan-Meier Plotter enrollment data analysis revealed that patients with overexpressed STX6 had substantially worse OS and PFS than individuals with low STX6 expression. Retrospective study revealed a significant (P<0.05) correlation between the STX6 expression and tumor classifications, tumor stage, peritoneal carcinomatosis index (PCI), and PFS survival of patients. Western blot and PCR findings for fresh samples showed that STX6 was overexpressed in both primary lesions and PM nodules of OC. SKOV3 cell proliferation was shown to be dramatically reduced by STX6 knockdown and promoted by STX6 overexpression, according to the in vitro experiments. STX6 may increase the progression of epithelial OC by encouraging the proliferation of cancer cells, indicating that STX6 was a viable therapeutic target of epithelial OC.

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

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

Inter observer reliability for peritoneal carcinomatosis at computed tomography.

To determine whether there is inter-observer reliability between radiologists for reporting peritoneal carcinomatosis and computed tomography peritoneal carcinomatosis index estimation. The retrospective, cross-sectional study was conducted at Dow Institute of Radiology, Dow University of Health Sciences (DUHS), Ojha campus and comprised computed tomography scans done between December 1, 2019, to May 31, 2020, that were extracted from the institutional database searched using key words 'peritoneal carcinomatosis' and/or 'serosal deposits'. The first readers had 1-4 years of post-fellowship experience, while the 2nd readers were senior radiologists. Inter-observer reliability was assessed quantitatively and qualitatively for 15 peritoneal sites using, among other tolls, the Sugarbaker computed tomography peritoneal carcinomatosis index. Data was analysed using SPSS 21. Out of 236 subjects with mean age 53.6±13.6 years, there were 173(73.3%) females and 63(26.7%) males. The most common primary cancer was ovarian 145(61.4%), followed by colon 26(11%). The size of peritoneal deposit was not reported in 75(31.8%) cases. Of the 15 sites analysed, good agreement was not found in 7(46.7%). There was an excellent intra-class correlation for measuring computed tomography peritoneal carcinomatosis index scores among the radiologists irrespective of the grade of the faculty (>0.90). The inter-observer reliability was low, but good agreement for computed tomography peritoneal carcinomatosis index would encourage radiologists to use it in peritoneal cancer reporting.

The clinicopathological significance of TOP2A expression in malignant peritoneal mesothelioma

BackgroundMalignant peritoneal mesothelioma (MPM) is a rare malignant tumor with a high mortality rate and extremely poor prognosis. TOP2A expression is associated with cell proliferation and cell cycle progression. We aimed to demonstrate the expression profile of TOP2A in MPM and its correlation with clinicopathological features. MethodsClinicopathological information from 100 MPM cases was collected at Beijing Shijitan Hospital, Capital Medical University. Immunohistochemistry (IHC) was performed to evaluate TOP2A levels. The associations between TOP2A levels and clinicopathological features or prognosis were analyzed. Clinical follow-up data were reviewed to determine correlations among the pathological prognostic factors using the Kaplan–Meier estimator and univariate/multivariate Cox proportional hazards regression models. ResultsAmong the 100 MPM patients, there were 48 males and 52 females, with a median age of 54 years (range: 24–72 years). The cutoff curve was used to find the boundary value of the TOP2A-positive rate. TOP2A positive rate ≥ 11.97 % accounted for 48 % in tumor tissue. The TOP2A-positive rate was not associated with sex, age, asbestos exposure, peritoneal carcinomatosis index (PCI) score, or completeness of cytoreduction (CC) score in MPM. Univariate analysis revealed survival-related pathological parameters, including asbestos exposure, CA125, histological type, PCI score, CC score, Ki-67 index, and TOP2A positive rate. Multivariate analysis identified that asbestos exposure history, PCI score, Ki-67 proliferation index and TOP2A positive rate in tissue are independent prognostic factors. ConclusionsHigh expression of TOP2A is linked to better prognosis of MPM.

Peritoneal carcinomatosis index and overall survival in patients taken to cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

The peritoneal carcinomatosis (PC) secondary to gastrointestinal or gynecological cancer has increased its incidence. It has a worse prognosis compared to other sites of metastasis. The peritoneal carcinomatosis index (PCI) establishes overall survival in patients with gastrointestinal or gynecological tumors and carcinomatosis. To evaluate the relationship of PCI to overall survival (OS) and recurrence-free survival (RFS) in patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC). A descriptive, retrolective study of 80 charts of patients with CP was conducted. We included patients with colon, ovarian, appendicular, pseudomyxoma and gastric tumors with CP treated with CRS plus HIPEC. The OS and RFS were determined according to the type of adenocarcinoma and the degree of differentiation. The OS and RFS were determined in months in patients with PCI > 15 PCI as well as in patients with PCI < 15 considering the tumor of origin. Patients with ovarian tumors and pseudomyxoma with PCI < 15 presented OS > 70 months, compared to patients with gastric tumors (4 months). The PCI and histology are predictors of OS. Patients with ovarian tumors and PCI < 15 have higher OS, similar to pseudomyxomas. RFS was also higher in patients with PCI < 15.

Methods to increase the effectiveness of cytoreductive surgical interventions in patients with complicated disseminated tumors of the abdominal cavity and pelvis

The expediency of performing two-stage cytoreductive interventions in patients with complicated disseminated tumors of the abdominal cavity and pelvis is presented. Ninety-two patients with complicated disseminated tumors of the abdominal cavity and pelvis were examined into two groups. The main group consisted of 33 patients who received surgical treatment by two-stage cytoreductive surgery. The control group included 59 patients who underwent single-stage cytoreductive operations. In both groups, life-threatening complications were dominated by primary tumor necrosis (main group, n = 15; control group, n = 31) and impaired intestinal patency (main group, n = 12; control group, n = 16, respectively). The average Charlson comorbidity index was 7.85 1.37 and 7.53 1.5 points, respectively. Anesthetic risk of grades IIIIV according to the classification of the American Society of Anesthesiologists was detected in 23 (69.7%) and 45 (76.27%) patients of the main and control groups, respectively. Functional status of 23 points on the Eastern Cooperative Oncological Group was established in 23 (69.7%) and 46 (77.9%) patients of the main and control groups, respectively. The peritoneal carcinomatosis index was significantly higher in the main group (13.1 6 vs 9.9 4.8 points) than in the control group (p = 0.012). A comparative analysis of the results obtained in the treatment of the main and control groups demonstrated that the two-stage cytoreductive surgical interventions can reduce the frequency of postoperative complications, primarily ClavienDindo grades IIIIV from 40.7 to 18.2% (p = 0.049) and mortality from 16.9% to 9.1% (p = 0.468) and increase the frequency of achieving complete cytoreduction from 49.1% to 90.9% (p = 0.002) and the frequency of intraperitoneal hyperthermic chemoperfusion from 40.7 to 93.9% (p 0.001). Thus, two-stage cytoreductive surgical interventions are a safe and effective technique in the surgical treatment of complicated disseminated tumors of the abdominal cavity and pelvis.

Comparison of 68GA-FAPI-04 PET/CT and 18F-FDG PET/CT findings in peritonitis carcinomatosa cases.

This study was conducted to compare the diagnostic accuracy of gallium-68-radiolabeled fibroblast activation protein inhibitor (68Ga-FAPI-04), positron emission tomography/computed tomography (PET/CT), and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT based on the peritoneal carcinomatosis (PC) index for detecting peritoneal metastases of various cancer types, and to evaluate the potential benefits of FAPI PET/CT in patients with peritoneal metastases. This retrospective study included 57 patients with peritoneal metastases between November 2020 and December 2021. All patients underwent 68Ga-FAPI-04 PET/CT and 18F-FDG PET/CT scans within 7 days. Among the 57 patients included, 32 (56.1%) were male and the median age was 54 years (22-86 years). In the visual evaluation made from a total of 13 quadrants on the abdominopelvic peritoneal surfaces, positive findings were observed in 111 quadrants in 39 patients by 18F-FDG PET/CT and in 280 quadrants in 57 patients by 68Ga-FAPI-04 PET/CT (P<0.001). The maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) values of 68Ga-FAPI-04 PET/CT for the PC lesions were significantly higher than the SUVmax and TBR values of 18F-FDG PET/CT in all patients and in all quadrants (SUVmax 6.45 vs 4.1; P<0.001; TBR 14.9 vs 6.8; P<0.001). Gallium-68-FAPI-04 PET/CT showed superior sensitivity compared to 18F-FDG PET/CT in both quantitative and visual evaluations of PC. Considering the low background activity and higher specific activity uptake values, 68Ga-FAPI-04 PET/CT helped improve diagnostic accuracy.

Abstract 150: A 515 tumor specimens collection from surgery to benchtop: the WFORCE organoid experience in personalized research

Abstract Introduction: Patient tumor organoids (PTOs) are a new and developing preclinical model in cancer research. However, there is variation in protocols between centers and lack of consistency in important variables, impacting PTO culture success. In this study, we analyzed factors in clinical data and tumor tissue processing to determine optimal conditions for cell isolation and PTO success. Methods: Under IRB approval, tumor tissues from primary and metastatic sites were procured in clinically indicated surgeries then dissociated using a standardized protocol. PTOs were fabricated using collagen-hyaluronic acid ECM and underwent drug screening at 10 days post fabrication, where viability was assessed. Clinical and tissue processing inputs such as type of primary, peritoneal carcinomatosis index (PCI), prior surgery or neoadjuvant chemotherapy, presence of mucin, tissue digestion time, specimen mass, digestion time, and the diameter of isolated cells were analyzed. These factors were assessed by calculating the Pearson Correlation Coefficient (r) and best fit modeling to determine the effect on outputs including tissue viability as measured by % of viable cells using an automated cellular counter, viable cells per mg tissue, and PTO log10 viability by Promega 3D Cell Titer Glo assay. Results: From December 2018-July 2022, 515 tumors from 286 patients with 25 primary types were processed for cellular isolation and PTO fabrication. 407 (79%) provided PTOs for therapeutic testing, with 354 (69%) providing sufficiently viable PTOs for therapeutic interrogation. The most common primary tumor type accrued was appendiceal cancer (n=223, 43%). Tissues processed at 24 hours did not differ in viability outputs when compared to tissues processed immediately (p&amp;gt;0.05). Tissue % viability was better maintained in larger specimens (r=.18, p&amp;lt;0.001), resulting in more viable cells per mg of tissue (r=.12, p=0.009) while it was negatively related to larger cell diameter (r=-.32, p&amp;lt;0.001). The number of viable cells per mg of tumor correlated to higher post-processing cell counts (r=.49, p&amp;lt;0.001) while it was decreased by longer digestion times (r=-.11, p=0.017). Finally, PTO log10 viability, correlated with higher burden of disease as measured by PCI scores (r=.35, p&amp;lt;0.001), larger specimens (r=.19, p&amp;lt;0.001), mucinous tumors (PTO log10 viability 5.46 vs 5.17, p=0.01), and tissues with higher cellular viability (r=.31, p&amp;lt;0.001), while it was negatively impacted by neoadjuvant chemotherapy (5.06 vs 5.41, p&amp;lt;0.001). Conclusions: Higher rates of successful PTO fabrication are obtained in patients with untreated tumors, more aggressive biologic behavior, and increased tumor burden. Creating a unified protocol for tissue processing, agnostic to tumor type, will facilitate incorporation of tissue from the operating room to research protocols with wider translational implications. Citation Format: Steven Donald Forsythe, Richard A. Erali, Preston Laney, William Meeker, Salomat Abdulkhuseynova, Nadeem Wajih, Nicholas Edenhoffer, Cecilia R. Schaaf, Hemamyammal Sivakumar, Aleksander Skardal, Roy E. Strowd, Stephen B. Tatter, Clancy J. Clark, Reese W. Randle, Perry Shen, Edward A. Levine, Ralph B. D'Agostino, Shay Soker, Konstantinos I. Votanopoulos. A 515 tumor specimens collection from surgery to benchtop: the WFORCE organoid experience in personalized research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 150.

The robotic future of minimally invasive cytoreduction and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been increasingly utilized for peritoneal surface malignancies. This has been commonly utilized for a variety of neoplasms, but, especially mucinous neoplasms of the appendix, ovarian cancer, gastric cancer, colorectal cancer and mesothelioma. Traditionally, CRS/HIPEC has been performed as an open, extensive operation associated with prolonged hospitalization. However, when the peritoneal carcinomatosis index (PCI) is small (<10), minimally invasive approaches can be considered. Such less invasive approaches may be associated with improved postoperative recovery, less complications while preserving oncologic outcomes. The robotic platform offers distinct advantages over laparoscopy with superior visualization and ergonomics which account for its increased utilization in oncologic surgery. Herein, we review available data on minimally invasive approaches to CRS/HIPEC procedures, focusing on patient selection and comparative studies to open CRS/HIPEC. We summarize the existing initial studies on robotically assisted CRS/HIPEC and provide technical insights about our approach to robotically assisted CRS/HIPEC. Current data suggests that treatment of peritoneal surface malignancies with minimally invasive CRS/HIPEC is feasible in selected cases and is associated with improved postoperative recovery. The robotically assisted platform for CRS/ HIPEC deserves further investigation and may improve outcomes after this procedure in the future for carefully selected patients with low PCI.

MP26-08 PREDICTORS OF ABDOMINAL ADHESIONS BEFORE ABDOMINAL SURGERY: DEVELOPMENT OF A CLINICAL NOMOGRAM

You have accessJournal of UrologyCME1 Apr 2023MP26-08 PREDICTORS OF ABDOMINAL ADHESIONS BEFORE ABDOMINAL SURGERY: DEVELOPMENT OF A CLINICAL NOMOGRAM Olivia Alessandra Voglino, Giorgio Guarnotta, Elisa Mancini, Carmen Gravina, Riccardo Lombardo, Giorgia Tema, Antonio Francesco Maria Cicione, Giovanni Di Pierro, Giorgio Franco, Costantino Leonardo, Alessandro Sciarra, Stefano Salciccia, Antonio Carbone, Antonio Luigi Pastore, Di Marco Massimiliano, Andrea Tubaro, and Cosimo De Nunzio Olivia Alessandra VoglinoOlivia Alessandra Voglino More articles by this author , Giorgio GuarnottaGiorgio Guarnotta More articles by this author , Elisa ManciniElisa Mancini More articles by this author , Carmen GravinaCarmen Gravina More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Giorgia TemaGiorgia Tema More articles by this author , Antonio Francesco Maria CicioneAntonio Francesco Maria Cicione More articles by this author , Giovanni Di PierroGiovanni Di Pierro More articles by this author , Giorgio FrancoGiorgio Franco More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Alessandro SciarraAlessandro Sciarra More articles by this author , Stefano SalcicciaStefano Salciccia More articles by this author , Antonio CarboneAntonio Carbone More articles by this author , Antonio Luigi PastoreAntonio Luigi Pastore More articles by this author , Di Marco MassimilianoDi Marco Massimiliano More articles by this author , Andrea TubaroAndrea Tubaro More articles by this author , and Cosimo De NunzioCosimo De Nunzio More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003254.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intraabdominal adhesions are nonspecific complications related to prior abdominal surgery. Aim of our study was to evaluate the possible preoperative predictors of abdominal adhesions. METHODS: A consecutive series of patients undergoing abdominal surgery were prospectively enrolled from January 2021 to October 2022. Patients were preoperatively evaluated with clinical history and physical examination. A contrast enhanced CT scan was performed before the procedure and on the portal phase intrabdominal adhesions were recorded. Intraoperative adhesions were graded according to the peritoneal carcinomatosis index. Predictors of intraoperative adhesions were evaluated using logistic regression analysis. A nomogram was developed based on the logistic regression model. RESULTS: Overall, 104 patients with a median age of 69 (64/73) were enrolled. On abdominal CT 58/104 ( 56%) presented signs of abdominal adhesions and 46/104 (44%) presented adhesions intraoperatively. Median PCI was 5 (3/7). Patients with intraoperative abdominal adhesions presented more frequently Metabolic Syndrome (37/46: 82% vs 30/58: 51%, p<0,05), previous abdominal surgery (32/46:69% vs 21/58: 37%, p<0,01), ischemic heart disease (IHD) (16/46:36 % vs 9/58: 16 %, p<0,05) and signs of adhesions on abdominal CT (40/46: 87% vs 18/58:31%; p<0,05). On univariate analysis, metabolic syndrome, IHD, prior abdominal surgery and CT adhesions were predictors of intraoperative adhesions. On multivariate analysis, metabolic syndrome, abdominal surgery and CT adhesions were predictors of intraoperative adhesions. We developed a clinical nomogram to predict adhesions with an AUC of 0,85 and a clinical net benefit in the range of probabilities between 20 and 80%. CONCLUSIONS: Metabolic syndrome, prior abdominal surgery and CT adhesions are predictors of intraoperative adhesions. The present nomogram may be used after external validation to counsel patients on the presence of adhesions before abdominal surgery. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e355 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Olivia Alessandra Voglino More articles by this author Giorgio Guarnotta More articles by this author Elisa Mancini More articles by this author Carmen Gravina More articles by this author Riccardo Lombardo More articles by this author Giorgia Tema More articles by this author Antonio Francesco Maria Cicione More articles by this author Giovanni Di Pierro More articles by this author Giorgio Franco More articles by this author Costantino Leonardo More articles by this author Alessandro Sciarra More articles by this author Stefano Salciccia More articles by this author Antonio Carbone More articles by this author Antonio Luigi Pastore More articles by this author Di Marco Massimiliano More articles by this author Andrea Tubaro More articles by this author Cosimo De Nunzio More articles by this author Expand All Advertisement PDF downloadLoading ...

Perioperative outcomes of cytoreductive surgery for tumours of colorectal or appendiceal origin with ovarian involvement.

Ovarian metastases (OM) are a common site for metastases in gastrointestinal tumours with peritoneal disease. This study aimed to evaluate perioperative complications between patients with and without OM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal/colorectal cancer. Female patients undergoing CRS ± HIPEC for appendiceal/colorectal tumours at a single centre from 2009 to 2020 were analysed. Patients were grouped according to presence or absence of OM at the time of CRS. The study included 318 patients, 72 (22.6%) had OM. Operation duration was longer for patients with OM (332 vs. 276 min, p < 0.0001). Patients with OM achieved higher rates of complete cytoreduction (93% vs. 79%, p = 0.006) despite a higher peritoneal carcinomatosis index (13vs. 7, p < 0.001)and were more likely to require a blood transfusion (32% vs. 19%, p = 0.024) and a stoma (24% vs.10%, p = 0.005). Increasing age and presence of abdominal symptoms were independent predictors of major and all-cause morbidity, respectively. The presence of abdominal symptoms was independently associated with all-cause morbidity in the OM group. These results may assist with preoperative counselling. Prospective multicentre datasets are needed to evaluate morbidity in one- versus two-stage approaches for those with abdominal symptoms and OM.

Development and Validation of Nomograms to Predict Survival in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin

Pseudomyxoma peritoni, a rare condition characterized by mucinous ascites and peritoneal deposits, mainly originates from a ruptured mucinous appendix tumor and is considered an indolent disease but can progress and become fatal. Optimal treatment to improve cure and survival rates involves complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Accurate predictive models are useful in supporting and informing treatment strategies and stratifying patient follow-up. To evaluate the prognostic significance of clinically important variables and generate validated nomograms to predict overall (OS) and disease-free survival (DFS) following CCRS and hyperthermic intraperitoneal HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin. This retrospective study used prospectively collected data on patients who had cytoreductive surgery (CRS) and HIPEC in a single institution between 1994 and 2018. The cohort was randomly allocated into development (70%) and validation (30%) sets. Univariate and multivariate analyses were performed with Cox proportional hazards regression. A prediction model was developed with significant prognostic factors identified by multivariate analysis. The model's prognostic performance was evaluated with the concordance index (C index). The nomogram was calibrated by comparing the predicted and observed probabilities. Of 2637 CRS and HIPEC operations, 1102 patients (female, 64.4%; median age [IQR], 57.0 [48.0-66.0] years) (41.8%) had CCRS for PMP of appendiceal origin. Elevated tumor markers, peritoneal carcinomatosis index, gastrectomy, and tumor grade were independent predictive factors for DFS. Gender, age, elevated tumor makers, peritoneal carcinomatosis index, and tumor grade influenced OS. The nomograms were generated with respective prognostic factors. The nomograms showed good performance in predicting survival. Median OS of the cohort was 16.5 years (95% CI, 13.7-19.2) with a 5-year probability of survival of 80.2%. The median DFS was 10.3 years (95% CI, 7.2- 13.3) and the 5-year probability of recurrence-free survival was 60.5%. Clinically important independent predictors for survival and recurrence were selected to develop the nomograms for OS and DFS. These 2 nomograms are user friendly and useful tools for patient management with clinical trial design applications.

Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma.

Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective. A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS±HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery. Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p=0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p=0.039) and peritoneal carcinomatosis index >10 (p=0.009), were factors independently associated with worse OS. Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.

Influence of Extraperitoneal Metastases on the Curative-Intent Management of Colorectal Peritoneal Metastases.

Selected patients with colorectal cancer peritoneal metastasis (CRPM) and extraperitoneal disease could be treated radically with a multimodal approach combining complete cytoreductive surgery, thermoablation, radiotherapy, and systemic and intraperitoneal chemotherapy. The impact of extraperitoneal metastatic sites (EPMS) in this setting remains unclear. Patients with CRPM undergoing complete cytoreduction in 2005-2018 were grouped in: peritoneal disease only (PDO), one EPMS (1+EPMS), two or more EPMS (2+EPMS). A retrospective analysis compared overall survival (OS) and postoperative outcomes. Of 433 patients, 109 had 1+EPMS and 31 had 2+EPMS. Overall, 101 patients had liver metastasis, 19 lung metastasis, and 30 retroperitoneal lymph node (RLN) invasion. The median OS was 56.9 months. There was no significant OS difference between PDO and 1+EPMS groups (64.6 and 57.9 months, respectively), whereas OS was lower in the 2+EPMS group (29.4 months, p=0.005). In multivariate analysis, 2+EPMS [hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.33-6.12, p = 0.007], Sugarbaker's Peritoneal Carcinomatosis Index (PCI) >15 (HR 3.86, 95% CI 2.04-7.32, p< 0.001), poorly differentiated tumors (HR 2.62, 95% CI 1.21-5.66, p = 0.015), and BRAF mutation (HR 2.10, 95% CI 1.11-3.99, p = 0.024) were independent poor prognostic factors, while adjuvant chemotherapy was beneficial (HR 0.33, 95% CI 0.20-0.56, p < 0.001). Patients with liver resection did not show higher severe complication rates. In patients with CRPM selected for a radical surgical approach, limited extraperitoneal disease involving one site, notably the liver, does not seem to significantly impair postoperative results. RLN invasion appeared as a poor prognostic factor in this population.

Extreme cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of peritoneal metastasis.

It was aimed to define the oncologic concept of "extremeness" in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) to determine morbidity-mortality results and final oncologic outcomes. Prospectively recorded data of 666 patients with peritoneal metastases who had undergone CRS/HIPEC between 2007 and 2020 were analyzed. Patients were divided into two groups as extreme (n= 371) and non-extreme (n= 295). Extreme CRS was defined as resection of ≥5 major organs or creation of ≥2 bowel anastomoses or peritoneal carcinomatosis index (PCI)≥ 15 or re-cytoreductive surgery. More CC-1 or CC-2 cytoreduction (p <.001), increased mortality and morbidity (p <.001), prolonged operative time (p <.001), increased intraoperative erythrocyte suspension (p <.001), albumin (p <.001), fresh frozen plasma (FFP) (p <.001), and post-operative erythrocyte suspension (p <.001) usage were found in the extreme CRS/HIPEC group. Operative time, CC-1 or CC-2 cytoreduction, presence of ostomy, development of infection, and use of intra-operative albumin and FFP were found to be independent prognostic factors in Cox regression analysis. Three and five-year survival rates were significantly lower in the extreme CRS/HIPEC group (p <.001). High-volume peritoneal metastatic disease can be completely resected with extreme cytoreduction in carefully selected patients responsive to chemotherapy. Since the significant morbi-mortality related to the treatment of peritoneal metastasis is a real concern, it should be considered in experienced complex cancer centers that provides relatively better oncological outcomes compared to conventional treatments.

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition.

A disintegrin and metalloprotease 12 (ADAM12) and epithelial‑mesenchymal transition (EMT) are linked in the metastasis of various types of cancer. The present study aimed to assess the ability of ADAM12 to induce EMT and its potential as a therapeutic target for colorectal cancer (CRC). ADAM12 expression in CRC cell lines, CRC tissues and a mouse model of peritoneal metastasis was assessed. The effect of ADAM12 on CRC EMT and metastasis was investigated using ADAM12‑pcDNA6‑myc and ADAM12‑pGFP‑C‑shLenti constructs. ADAM12 overexpression enhanced the proliferation, migration, invasion and EMT of CRC cells. The phosphorylation levels of factors associated with the PI3K/Akt pathway were also increased by ADAM12 overexpression. The knockdown of ADAM12 reversed these effects. ADAM12 expression and the loss of E‑cadherin expression were significantly associated with poorer survival compared with other expression statuses of both proteins. In a mouse model of peritoneal metastasis, overexpression of ADAM12 induced increased tumor weight and peritoneal carcinomatosis index compared with that in the negative control group. Conversely, knockdown of ADAM12 reversed these effects. Furthermore, E‑cadherin expression was significantly decreased by overexpression of ADAM12 compared with in the negative control group. By contrast, E‑cadherin expression was increased by knockdown of ADAM12 compared with in the negative control group. ADAM12 overexpression contributed to CRC metastasis by regulating EMT. In addition, in the mouse model of peritoneal metastasis, ADAM12 knockdown exhibited strong anti‑metastatic action. Consequently, ADAM12 may be considered a therapeutic target for CRC metastasis.

Laparoscopic right hemicolectomy with aortocaval lymphadenectomy, and pelvic peritoneum partial resection for ascending colon cancer.

The aim of this video is to present the procedural details of laparoscopic right hemicolectomy with aortocaval (infrarenal aortic bifurcation) lymphadenectomy, partial resection of the pelvic peritoneum (peritoneal carcinomatosis index, 3), and hyperthermic intraperitoneal chemotherapy in a patient who received neoadjuvant chemotherapy for stage IVc colorectal cancer. The total operation time was 290 minutes, and the patient was discharged on a postoperative day 13 without any complications. No postoperative complications occurred until postoperative day 60. The pathological stage of the tumor was determined to be T3N2bM1c. The pelvic peritoneal nodule was pathologically confirmed as a metastatic lesion. Among the 12 harvested aortocaval lymph nodes, 6 were metastatic lymph nodes. The minimally invasive approach was safe and feasible in this highly selected patient with colon cancer, aortocaval lymph nodes, and peritoneal metastases.

Development of a Novel Intra-Operative Score to Record Diseases' Anatomic Fingerprints (ANAFI Score) for the Prediction of Complete Cytoreduction in Advanced-Stage Ovarian Cancer by Using Machine Learning and Explainable Artificial Intelligence.

The Peritoneal Carcinomatosis Index (PCI) and the Intra-operative Mapping for Ovarian Cancer (IMO), to a lesser extent, have been universally validated in advanced-stage epithelial ovarian cancer (EOC) to describe the extent of peritoneal dissemination and are proven to be powerful predictors of the surgical outcome with an added sensitivity of assessment at laparotomy of around 70%. This leaves room for improvement because the two-dimensional anatomic scoring model fails to reflect the patient's real anatomy, as seen by a surgeon. We hypothesized that tumor dissemination in specific anatomic locations can be more predictive of complete cytoreduction (CC0) and survival than PCI and IMO tools in EOC patients. (2) Methods: We analyzed prospectively data collected from 508 patients with FIGO-stage IIIB-IVB EOC who underwent cytoreductive surgery between January 2014 and December 2019 at a UK tertiary center. We adapted the structured ESGO ovarian cancer report to provide detailed information on the patterns of tumor dissemination (cancer anatomic fingerprints). We employed the extreme gradient boost (XGBoost) to model only the variables referring to the EOC disseminated patterns, to create an intra-operative score and judge the predictive power of the score alone for complete cytoreduction (CC0). Receiver operating characteristic (ROC) curves were then used for performance comparison between the new score and the existing PCI and IMO tools. We applied the Shapley additive explanations (SHAP) framework to support the feature selection of the narrated cancer fingerprints and provide global and local explainability. Survival analysis was performed using Kaplan-Meier curves and Cox regression. (3) Results: An intra-operative disease score was developed based on specific weights assigned to the cancer anatomic fingerprints. The scores range from 0 to 24. The XGBoost predicted CC0 resection (area under curve (AUC) = 0.88 CI = 0.854-0.913) with high accuracy. Organ-specific dissemination on the small bowel mesentery, large bowel serosa, and diaphragmatic peritoneum were the most crucial features globally. When added to the composite model, the novel score slightly enhanced its predictive value (AUC = 0.91, CI = 0.849-0.963). We identified a "turning point", ≤5, that increased the probability of CC0. Using conventional logistic regression, the new score was superior to the PCI and IMO scores for the prediction of CC0 (AUC = 0.81 vs. 0.73 and 0.67, respectively). In multivariate Cox analysis, a 1-point increase in the new intra-operative score was associated with poorer progression-free (HR: 1.06; 95% CI: 1.03-1.09, p < 0.005) and overall survival (HR: 1.04; 95% CI: 1.01-1.07), by 4% and 6%, respectively. (4) Conclusions: The presence of cancer disseminated in specific anatomical sites, including small bowel mesentery, large bowel serosa, and diaphragmatic peritoneum, can be more predictive of CC0 and survival than the entire PCI and IMO scores. Early intra-operative assessment of these areas only may reveal whether CC0 is achievable. In contrast to the PCI and IMO scores, the novel score remains predictive of adverse survival outcomes.