Construction and evaluation of a nomogram for predicting the prognosis of patients with colorectal cancer with peritoneal carcinomatosis treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.

On the difficulties and pains in managing peritoneal metastasis from gastrointestinal cancer in China / 中华胃肠外科杂志

Modern clinical oncology has made great achievements over the last century. However, peritoneal metastasis from gastrointestinal cancer, as one of three most common metastasis modalities, was not re-recognized until the end of the last century, and a normative diagnosis and treatment system has been gradually beginning to be formed until today. This comment is to review the development history, reflect on the lessons and experiences in clinical practice, analyze the difficulties on redefinition, deep understanding and clinical management, and pain points on theory construction, technique practice and discipline construction, in the field of gastrointestinal cancer peritoneal metastasis. We suggested a solution to the difficulties and pain points by realizing the fact of burden of peritoneal metastasis, reinforcing technical training, and promoting collaborative researches, aiming to provide reference for the steady development of peritoneal surface oncology.

Efficacy of 1 384 cases of peritoneal carcinomatosis underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy / 中华胃肠外科杂志

Objective: Peritoneal carcinomatosis refers to a group of heterogeneous (primary or secondary) malignancies in the surface of the peritoneum. Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) is a comprehensive treatment strategy aiming at peritoneal carcinomatosis. This study analyzed the efficacy and safety of CRS+HIPEC in patients with peritoneal carcinomatosis, and explored prognostic factors. Methods: In this descriptive case-series study, the clinicopathological data of 1384 consecutive patients with peritoneal carcinomatosis treated in Zhongnan Hospital of Wuhan University (330 patients) and Shijitan Hospital of Capital Medical University (1054 patients) from January 2004 to January 2020 were collected retrospectively. Treatment patterns of CRS+HIPEC characteristics (operative time, number of resected organs, number of stripped peritoneum, number of anastomosis, and HIPEC regimens), safety [blood loss volume, postoperative severe adverse event (SAE) and treatment outcome], survival time and prognostic factors influencing survival were analyzed. The SAE was defined as grade III-IV adverse event according to the Peritoneal Surface Oncology Group International Textbook. Perioperative period was defined from the day of CRS+HIPEC to postoperative 30th day. OS was calculated from the day of CRS+HIPEC to the date of death or the last follow-up. Kaplan-Meier method was used for survival analysis, and log-rank test was used for comparison between groups. Cox regression model was used to identify the prognostic factors. Results: Among 1384 peritoneal carcinomatosis patients, 529 (38.2%) were male; median age was 55 (10-87) years old; median body mass index (BMI) was 22.6 kg/m(2); peritoneal carcinomatosis of 164 (11.8%) patients were from gastric cancer, 287 (20.7%) from colorectal cancer, 356 (25.7%) from pseudomyxoma peritonei, 90 (6.5%) from malignant peritoneal mesothelioma, 300 (21.7%) from gynecological cancer or primary peritoneal carcinoma, and 187 (13.5%) from retroperitoneal sarcoma, lung cancer, breast cancer, and other rare tumors. The median duration of CRS+HIPEC was 595 (90-1170) minutes, median number of resected organs was 2 (0-10), median number of resected peritoneal area were 4 (0-9), median peritoneal cancer index (PCI) was 21(1-39). Completeness of cytoreduction (CC) score of 0-1 was observed in 857 cases (61.9%). Regarding HIPEC regimens, there were 917 cases (66.3%) with cisplatin plus docetaxel, 183 cases (13.2%) with cisplatin plus mitomycin, 43 cases (3.1%) with adriamycin plus ifosfamide, and the other 240 cases (17.3%) with modified regimens. Perioperative SAE developed in 331 peritoneal carcinomatosis patients (23.9%) with 500 cases, of whom 21 patients (1.5%) died during the perioperative period due to ineffective treatment, while the others recovered after active treatment. During median follow-up time of 8.6 (0.3-82.7) months, there were 414 deaths (29.9%). The median OS was 38.2 months (95% CI: 30.6-45.8), and the 1-, 3-, 5-year survival rate was 73.5%, 50.4% and 39.3%, respectively. The median OS of peritoneal carcinomatosis patients from gastric cancer, colorectal cancer, pseudomyxoma peritonei, malignant peritoneal mesothelioma and female genital cancer or primary peritoneal carcinomatosis was 11.3 months (95% CI: 8.9-13.8), 18.1 months (95% CI: 13.5-22.6), 59.7 months (95% CI: 48.0-71.4), 19.5 months (95% CI: 6.0-33.0) and 51.7 months (95% CI: 14.6-88.8), respectively, and the difference among groups was statistically significant (P<0.001). Univariate and multivariate analyses revealed that the primary gastric cancer (HR=4.639, 95% CI: 1.692-12.724), primary colorectal cancer (HR=4.292, 95% CI: 1.957-9.420), primary malignant peritoneal mesothelioma (HR=2.741, 95% CI: 1.162-6.466), Karnofsky performance status (KPS) score of 60 (HR=4.606, 95% CI: 2.144-9.895), KPS score of 70 (HR=3.434, 95% CI: 1.977-5.965), CC score of 1 (HR=2.683, 95% CI: 1.440~4.999), CC score of 2-3 (HR=3.661,95% CI: 1.956-6.852) and perioperative SAE (HR=2.588, 95% CI: 1.846-3.629) were independent prognostic factors influencing survival with statistically significant differences (all P<0.05). Conclusions: CRS+HIPEC is an effective integrated treatment strategy for patients with peritoneal carcinomatosis, which can prolong survival with acceptable safety. Preoperative evaluation of patients' general condition is necessary and CRS+HIPEC should be carefully considered to perform for patients with preoperative KPS score <80. During the operation, the optimal CRS should be achieved on condition that safety is granted. In addition, it is necessary to prevent perioperative SAE to reduce the risk of death in peritoneal carcinomatosis patients.

Fundamental pathological mechanisms underlying gastro-intestinal cancer peritoneal metastasis / 中华胃肠外科杂志

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.