BACKGROUND:The benefit of secondary cytoreduction surgery (SeCRS) followed by olaparib maintenance therapy for recurrent ovarian cancer has not been clearly demonstrated. This study aimed to evaluate the role of SeCRS combined with olaparib for patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer. METHODS:This multi-center retrospective study analyzed patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer treated between July 2015 and August 2024. Overall survival (OS) and progression-free survival (PFS) were used to measure treatment effectiveness. Adverse events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. RESULTS:Among 259 patients, 124 were treated with SeCRS followed by platinum-based chemotherapy (the surgery group), and 135 were treated with platinum-based chemotherapy alone (the chemotherapy group). All patients received olaparib tablets until disease progression. The median PFS in the surgery group was significantly longer than in the chemotherapy group (27.2 vs. 18.2 months; hazard ratio [HR], 0.46; 95 % confidence interval [CI], 0.35-0.62; p < 0.001). The median OS was significantly longer in the surgery group than in the chemotherapy group (68.1 vs. 50.5 months; HR, 0.57; 95 % CI 0.42-0.78; p < 0.001). The incidence and severity grades of adverse events did not differ significantly between the two groups. CONCLUSION:The findings of this study suggest that SeCRS followed by platinum-based chemotherapy and olaparib maintenance therapy results in longer OS and PFS than platinum-based chemotherapy followed by olaparib maintenance therapy alone for patients with BRCA-mutated platinum-sensitive recurrent ovarian cancer.

Background:Locally recurrent retroperitoneal sarcoma (RPS) poses substantial clinical challenges, especially in patients experiencing multiple recurrences. This study aims to evaluate the survival benefits conferred by repeated surgical resections in the management of recurrent RPS. Methods:A retrospective cohort study was conducted involving 56 patients who underwent repeated surgical resections for locally recurrent RPS at our institution between June 2016 and September 2023. Demographic, clinical, and histopathological variables- including age, sex, tumor differentiation, FNCLCC grade, prior radiotherapy and chemotherapy, surgical margin status, and postoperative complications -were collected and analyzed. Survival outcomes were assessed using Kaplan-Meier estimates and Cox proportional hazards models. Results:The median age of the cohort was 53 years (range: 28-72), with a male-to-female ratio of 30:26. Compared to a single resection, median overall survival (OS) improved with successive surgeries: 79.3 months for two surgeries, 158.0 months for three, and 181.7 months for four. However, OS declined to 121.9 months following five resections. Tumor differentiation and FNCLCC grade were significantly associated with survival outcomes. Multivariate analysis identified age, pathological subtype, tumor grade, and number of surgeries as independent prognostic factors. Although severe adverse events (SAEs) were recorded, no 30-day postoperative mortality occurred. Conclusions:Repeated surgical resection appears to confer substantial survival benefits in patients with locally recurrent RPS, underscoring the clinical value of surgical management in selected cases. These findings highlight the importance of individualized surgical strategies, while emphasizing the need for further investigation to optimize treatment paradigms.

BACKGROUND:Malignant peritoneal mesothelioma (MPM) is a rare but aggressive cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was the preferred choice for selected patients. The purpose of this study was to thoroughly examine the impact of the combined treatment and the prognostic variables, particularly the neutrophil-to-lymphocyte ratio (NLR). METHODS:Characteristics of MPM patients who underwent CRS combined HIPEC treatment, followed by adjuvant chemotherapy were retrospectively collected. The univariable analysis was performed to identify the decisive influential factor. Using Kaplan-Meier analysis, the cumulative probability of survival was determined. Using Univariate Cox analysis, the prognostic factors-particularly NLR-and its correlation with survival were assessed. In the multivariate Cox proportional hazards model, predictive factors that demonstrated significance in univariate analysis were used. The degree of connection between predictors and survival was evaluated through the use of hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS:A total of 64 patients were enrolled in this study. The 1, 3, 5 years survival rates were 70.3%, 65.6%, 59.4%, respectively. According to multivariate Cox analysis, patients' survival was found to be substantially associated with post-operative NLR (HR 0.180, 0.067-0.531), Ki-67 (HR 0.184, 0.024-0.817), post-operative neutrophil count (HR 0.228, 0.075-0.696), and bidirectional pathological type (HR, 0.375, 0.146-0.964). CONCLUSIONS:NLR is associated with the patients' prognosis after CRS combined HIPEC treatment.

Metastasis is one of the important factors leading to poor prognosis in patients with colon cancer. However, the molecular mechanism contributing to this cellular behaviour remains largely unknown. Here, RNA-seq analysis suggested that Fibronectin 1 (FN1) was significantly increased in metastatic colon cancer, which was associated with poor prognosis. FN1 enhanced colon cancer cell migration, invasion, and epithelial to mesenchymal transition (EMT) in vitro and promoted liver and lung metastasis of colon cancer in nude mice through RAP1B. Mechanistically, FN1 could interact with RAP1B by suppressing the interaction between RAP1B and the E3 ligase PARK2, relieving RAP1B ubiquitination modification and improving RAP1B protein stability. Furthermore, FN1-RAP1B activated Akt signalling pathway, leading to the phosphorylation and activation of CREB. Interestingly, CREB was found directly bound to the FN1 and TIMP1 promoter, respectively and increased FN1 and TIMP1 transcription, thereby establishing a positive regulatory feedback loop. Overall, our results elucidated that FN1 promotes colon cancer migration, invasion, and metastasis. FN1 may be used as the potential therapeutic target for colon cancer metastasis.

ObjectivesPancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group.MethodsA retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS).ResultsA total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified.ConclusionsThe combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.

Abstract Background Hepatocellular carcinoma with peritoneal metastasis (HCC-PM) has a poor outlook. Traditional treatments have limited effect on survival. The safety and efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) have been shown in other peritoneal cancers. This study evaluates the role of CRS + HIPEC in HCC-PM. Methods A retrospective analysis of HCC-PM patients treated with CRS + HIPEC at Beijing Shijitan Hospital from March 2017 to December 2023 was conducted, assessing clinical features, severe adverse events (SAEs), and overall survival (OS) rates. Results The study population comprised 10 HCC-PM patients who underwent CRS + HIPEC. The median peritoneal cancer index (PCI) was 25, and complete cytoreduction (CC0 ~ 1) was achieved in half of the patients. Three patients experienced SAEs within 30 days postoperatively. The 1-year, 3-year, and 5-year OS rates were recorded as 89.0%, 89.0%, and 21.0% respectively, with a median OS1 of 107.8 months and OS2 of 49.9 months. The median progression-free survival (PFS) was 5.0 months. Conclusion The application of CRS + HIPEC offers significant benefits to patients with HCC-PM. A selected group of patients may achieve prolonged PFS. Incorporating CRS + HIPEC into the treatment paradigm can thus be considered a strategic therapeutic option for patients with HCC-PM.

Objective To evaluate the effect of secondary cytoreductive surgery (SeCRS) followed by platinum-based chemotherapy (PBC) and olaparib tablets as maintenance therapy in patients with BRCA mutated recurrent epithelial ovarian cancer. Methods This was a retrospective study of a prospective database. We collected information on 623 patients diagnosed with BRCA mutated recurrent epithelial ovarian cancer, all of whom underwent SeCRS followed by PBC in combination with or without olaparib. Overall survival and progression-free survival were measured to evaluate treatment effectiveness. Results Of the 623 patients recruited, 240 underwent SeCRS plus hyperthermic intraperitoneal chemotherapy followed by PBC and olaparib maintenance therapy (Group A), 248 underwent SeCRS followed by PBC and olaparib maintenance therapy (Group B), and 135 underwent SeCRS followed by PBC only upon recurrence (Group C). The median progression-free survival for Group A was significantly longer than that for Group B (32.5 vs. 24.2 months, P<0.001), and Group B was significantly longer than Group C (24.2 vs. 15.1 months, P<0.001). The median overall survival for Groups A was significantly longer than that for Group B (71.4 vs. 63.5 months, P<0.001), and Group B was significantly longer than Group C (63.5 vs. 47.5 months, P<0.001). Conclusions This study suggested that SeCRS followed by PBC and olaparib maintenance therapy resulted in longer overall survival and progression-free survival than SeCRS followed by PBC only in patients with BRCA mutated recurrent ovarian cancer, especially in patients treated with SeCRS plus hyperthermic intraperitoneal chemotherapy.

Aim: To evaluate the effect of secondary cytoreductive surgery (SeCRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer patients. Methods: This retrospective study analyzed a prospective database. We collected information of 389 patients who were diagnosed with recurrent epithelial ovarian cancer. All patients underwent SeCRS with or without HIPEC. Overall survival and progression-free survival (PFS) were used to evaluate the treatment effectiveness. Results: Of the 389 patients collected, 123 underwent primary or interval cytoreductive surgery at initial treatment and SeCRS at recurrence (Group A), 130 underwent primary or interval cytoreductive surgery at initial and SeCRS plus HIPEC at recurrence (Group B), and 136 underwent primary or interval cytoreductive surgery plus HIPEC at initial and SeCRS plus HIPEC at recurrence (Group C). The median overall survival for Groups A, B, and C were 49.1 months (95% confidence interval [CI]: 47.6-50.5), 56.0 months (95% CI: 54.2-57.7), and 64.4 months (95% CI: 63.1-65.6), respectively. The median PFS for Groups A, B, and C were 13.1 months (95% CI: 12.6-13.5), 15.0 months (95% CI: 14.2-15.7), and 16.8 months (95% CI: 16.1-17.4), respectively. There were no significant difference in incidence and grade of adverse events among groups. Conclusions: This study suggested that SeCRS plus HIPEC followed by chemotherapy resulted in longer overall survival and PFS than only SeCRS followed by chemotherapy in patients with recurrent ovarian cancer, especially in patients who were treated with repeat HIPEC.

We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled—61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III–V AEs was 29.5

目的 评价股薄肌转移及双套管冲洗对复杂直肠阴道瘘治疗效果.方法 收集2013年5月至2017年5月在北京世纪坛医院行股薄肌转移治疗的40例直肠阴道瘘患者的临床资料,术后早期漏患者行双套管冲洗处理.记录手术成功率及术后并发症,比较术前及术后6个月SF-36生活质量评分及Wexner肛门失禁评分.结果 29例患者术后直肠阴道瘘顺利愈合,初始愈合率72.5％;11例患者术后早期漏行双套管冲洗治疗,9例愈合,2例失败,失败患者予以粪便转流.平均随访18个月,直肠阴道瘘修补成功率为95.0％,并发症发生率为17.5％,术后SF-36生活质量评分及Wexner肛门失禁评分明显改善(P<0.05).结论 股薄肌转移联合双套管冲洗是复杂直肠阴道瘘的有效治疗手段.

BACKGROUND:Pleural effusion (PE) is one of the most common complications of advanced recurrent ovarian cancer. However, no studies have revealed the risk factors for PE after surgery. The purpose of this study is to observe the incidence and risk factors of PE after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with late-stage and recurrent ovarian cancer.METHODS:A retrospective analysis of 77 patients with late-stage and recurrent ovarian cancer after CRS + HIPEC was conducted. According to the presence of PE within 7 days after operation, two groups were formed. The basic information, surgical process, and laboratory examinations of the two groups were analyzed and compared to conduct a regression analysis.RESULTS:The incidence of postoperative PE was 57.1% (44/77 patients). Among these patients, the prevalence of grade I-II and grade III-IV PE was 42.8% (33/77 patients) and 14.3% (11/77 patients), respectively. There were statistically significant differences between the two groups in terms of preoperative PE, the duration of surgery, intraoperative blood loss, postoperative level of albumin, intestinal involvement, and diaphragmatic involvement. Among these, preoperative PE and diaphragmatic involvement were identified as independent risk factors of postoperative PE.CONCLUSIONS:Patients with late-stage and recurrent ovarian cancer invariably develop postoperative PE after CRS + HIPEC. Preoperative PE and diaphragmatic involvement are independent risk factors of postoperative PE. It is estimated that the incidence of postoperative PE among patients with these two independent risk factors is approximately 100%. Hence, we should promote the prevention and treatment of PE to improve its prognosis.

Background: Breast cancer (BC) has the highest morbidity and the fifth-highest mortality rate among women in China. Peritoneal metastases from BC are rare, and presently, there are no guidelines or international consensus on its treatment. Patients with a prognosis of peritoneal carcinomatosis (PC) have poorer survival rates than patients with other regional metastases from BC. Methods: Four BC PC patients, who had undergone cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC), participated in this study. Clinicopathologic characteristics and overall survival (OS) data were collected and analyzed. Results: Patients' average age when they underwent CRS + HIPEC was 59.8 years. The average time of CRS + HIPEC was 8.8 h. The median number of resected organ areas was 7. Following CRS + HIPEC, each of the 4 patients survived for 31, 28, 16 and 52 months, respectively. There were no serious adverse events during the perioperative period. Conclusions: The study examined the detailed process of CRS + HIPEC and found that patients with BC PC may benefit from this treatment. The 4 cases provided evidence that the integrated therapy of CRS + HIPEC is a promising strategy that could improve outcomes for BC PC patients. Further, no serious adverse events (SAEs) occurred during the CRS + HIPEC perioperative period.

Background: Colorectal cancer (CRC) with lymphatic invasion is one of the critical prognostic factors in lymph node metastasis. Lymphangiogencsis has a significant effect on lymphatic metastasis and tumor progression. However, the significance of intratumoral and peritumoral lymphangiogenesis has been controversial in CRC. The aim of this study is to investigate the different role of introtumoral and peritumoral lymphangiogenesis in CRC progression and prognosis. Methods: Lymphangiogenesis of 120 CRC specimens, as measured by lymphatic vessel density (LVD), was examined by immunostaining for podoplanin, a lymphatic vessel-specific marker. The mean number of lymphatic vessels of three hotspots was measured in intratumoral and peritumoral areas as intratumoral LVD (LVDit) and peritumoral LVD (LVDpt), respectively. The association of LVDit and LVDpt with the clinicopathological findings and prognosis was investigated. Results: Compared to the peritumoral lymphatics, the intratumoral lymphatics were small, collapsed and irregular. The mean LVDpt was higher than the mean LVDit (P<0.001). LVDit was positively correlated with tumor size (P=0.009), tumor histologic grade (P=0.023), and overall survival (P=0.036). LVDpt was correlated with lymph node metastasis (P<0.001), tumor stage (P=0.004), and overall survival (P=0.016). Conclusions: LVDpt plays a prominent role in lymph node metastasis, whereas LVDit is more closely correlated with tumor growth and histopathological differentiation. Both LVDpt and LVDit contribute to CRC progression and prognosis.

Objective:s To evaluate the impacts of prior surgical scores(PSS) on the clinical efficacy and perioperative safety of cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) for pseudomyxoma peritonei(PMP).Methods:From the comprehensive PMP database, we collect the cases treated for the first time by CRS+ HIPEC, to form this study cohort. The clinicopathological features, PSS, CRS+ HIPEC details, overall survival(OS), and serious adverse events(SAEs) are systematically analyzed, to study the correlations between PSS and OS or SAEs.Results:335 PMP cases received standardized CRS+ HIPEC in this study. The median OS is 58.2 months for PSS-0 patients, 63.7 months for PSS-1, and 55.4 months for PSS-2/3, with no statistically significant differences in OS among the different PSS groups(χ 2=0.499, P=0.779). Subgroup analysis by pathologic types also found no statistically significant differences among the different PSS groups. Moreover, no significantly statistical differences are observed in overall SAEs(χ 2=0.625, P=0.722), CRS-related SAEs(χ 2=0.267, P=0.901), and non-CRS-related SAEs(χ 2=0.677, P=0.715), among the different PSS groups. Conclusions:PSS does not pose significant impacts on the efficacy and safety of CRS+ HIPEC for PMP patients at experienced treatment center.

目的 探讨核糖体结合蛋白1(RRBP1)与RABEX-5蛋白在结直肠癌组织中的表达与临床病理特征和预后的关系.方法 2015年8月—2016年8月收集外科手术治疗的86例结直肠癌患者的癌组织标本及相对应的癌旁组织标本;采用免疫组化染色法检测所有研究对象RRBP1、RABEX-5蛋白的表达水平,分析RRBP1、RABEX-5蛋白表达与结直肠癌患者临床病理特征的关系;并采用Cox比例风险模型分析影响结直肠癌患者预后的相关因素.结果 结直肠癌癌组织中RRBP1、RABEX-5蛋白阳性表达率(65.12％和62.79％)明显高于结肠癌癌旁组织RRBP1、RABEX-5蛋白阳性表达率(38.37％和36.05％),差异有统计学意义(P<0.001);TNMⅢ ～ Ⅳ期、肿瘤低分化、出现淋巴转移时结直肠癌患者PRRBP1、RABEX-5阳性表达率均升高(P<0.05);RRBP1阳性表达和阴性表达的中位总生存期分别为30个月和20个月,RABEX-5阳性表达和阴性表达中位总生存期分别为31个月和19个月;经单因素与多因素分析结果显示,TNMⅢ～Ⅳ期、肿瘤低分化、淋巴转移、RRBP1阳性表达、RABEX-5阳性表达均为影响结直肠癌患者预后的独立因素(P<0.01).结论 RRBP1蛋白与RABEX-5蛋白在结直肠癌组织中的表达水平均升高,且与结直肠癌患者的TNM分期、淋巴转移呈正相关,与分化程度呈负相关,RRBP1蛋白阳性表达与RABEX-5蛋白阳性表达均是结直肠癌预后的危险因素,二者可能作为结直肠癌诊断和预后的有效生物标志物.

OBJECTIVES A proportion of resectable pancreatic ductal adenocarcinoma (PDAC) patients display poorer survival due to profound local immune suppression. However, a pathological/morphological parameter that could functionally read out immune evasion and predict patient survival has not been defined. This study investigated the feasibility of heterotypic cell-in-cell (CIC) structures for immune cell cannibalism by tumor cells to serve as a parameter for survival prediction in resectable PDAC patients. METHODS A total of 410 samples from PDAC patients were examined using the methods of “EML” multiplex staining or immunohistochemistry (IHC). Prognostic CIC candidates were initially identified in samples plotted in tissue microarray (n=300), then independently validated in specimens from the First Affiliated Hospital of Sun Yat-Sen University (n=110). The Kaplan–Meier estimator and/or the Cox regression model were used for univariate and multivariate analysis. A nomogram was made using the Regression Modeling Strategies. RESULTS CICs were prevalent in cancerous (203/235) but not non-malignant tissues (15/147). Among the 4 CIC subtypes identified, 2 heterotypic subtypes with tumor cells internalizing CD45+ lymphocytes (LiT, mOS = 8 vs. 14.5 months, p = 0.008) or CD68+ monocytes (MiT, mOS = 7.5 vs. 15 months, p = 0.001), and overall CICs (oCIC, mOS = 10 vs. 27 months, p = 0.021), but not homotypic CICs (TiT, p = 0.089), were identified in univariate analysis as adverse prognostic factors of overall survival (OS) of PDAC. Notably, through cannibalism of immune cells by tumor cells, heterotypic CICs (L/MiT: LiT plus MiT) could independently predict shorter OS (HR = 1.85, p = 0.008) in multivariate analysis, with a performance comparable or even superior to traditional clinicopathological parameters such as histological grade (HR = 1.78, p = 0.012) and TNM stage (HR=1.64, p = 0.108). This was confirmed in the validation cohort, where L/MiT (HR = 1.71, p = 0.02) and tumor–node–metastasis (TNM) stage (HR = 1.66, p = 0.04) were shown to be independent adverse prognostic factors. Moreover, L/MiT stood out as the most prominent contributor in nomogram models constructed for survival prediction (area under the curve = 0.696 at 14 months), the dropout of which compromised prediction performance (area under the curve = 0.661 at 14 months). Furthermore, stratification analysis indicated that L/MiT tended preferentially to impact young and female patients (HR = 11.61, p CONCLUSION This was the first CIC profiling to be performed in PDAC, and is currently largest for human tumors. Subtyped CICs, as a valuable input to the traditional variables such as TNM stage, represent a novel type of prognostic factor. The formation of heterotypic L/MiT may be a surrogate for local immune evasion and predict poor survival, particularly in young female patients of resectable PDAC. Study Highlights Prior knowledge The post-operation survival periods of resectable pancreatic ductal adenocarcinoma (PDAC) patients range widely, and the search for reliable prognostic biomarkers is warranted. Although profound local immune suppression is implicated in PDAC progression and poor patient survival, a prognostic marker to read immune evasion in situ is not yet available. The impact of subtyped cell-in-cell (CIC) structures, which target either tumor or immune cells for internalization and death, on PDAC patient survival is not clear. Novelty of study This study presents the first CIC subtype profiling in PDAC, which is currently the largest of its type for human cancers. Subtyped CIC structures were identified and confirmed independently as a valuable prognostic factor for PDAC patients, with a performance comparable or superior to traditional variables such as tumor–node–metastasis (TNM) stage. The L/MiT heterotypic CIC subtype, surrogating a type of cellular immune evasion, could independently predict poor survival, particularly for young female patients of resectable PDAC.

OBJECTIVES A proportion of resectable pancreatic ductal adenocarcinoma (PDAC) patients display poorer survival due to profound local immune suppression. However, a pathological/morphological parameter that could functionally read out immune evasion and predict patient survival has not been defined. This study investigated the feasibility of heterotypic cell-in-cell (CIC) structures for immune cell cannibalism by tumor cells to serve as a parameter for survival prediction in resectable PDAC patients. METHODS A total of 410 samples from PDAC patients were examined using the methods of “EML” multiplex staining or immunohistochemistry (IHC). Prognostic CIC candidates were initially identified in samples plotted in tissue microarray (n=300), then independently validated in specimens from the First Affiliated Hospital of Sun Yat-Sen University (n=110). The Kaplan–Meier estimator and/or the Cox regression model were used for univariate and multivariate analysis. A nomogram was made using the Regression Modeling Strategies. RESULTS CICs were prevalent in cancerous (203/235) but not non-malignant tissues (15/147). Among the 4 CIC subtypes identified, 2 heterotypic subtypes with tumor cells internalizing CD45+ lymphocytes (LiT, mOS = 8 vs. 14.5 months, p = 0.008) or CD68+ monocytes (MiT, mOS = 7.5 vs. 15 months, p = 0.001), and overall CICs (oCIC, mOS = 10 vs. 27 months, p = 0.021), but not homotypic CICs (TiT, p = 0.089), were identified in univariate analysis as adverse prognostic factors of overall survival (OS) of PDAC. Notably, through cannibalism of immune cells by tumor cells, heterotypic CICs (L/MiT: LiT plus MiT) could independently predict shorter OS (HR = 1.85, p = 0.008) in multivariate analysis, with a performance comparable or even superior to traditional clinicopathological parameters such as histological grade (HR = 1.78, p = 0.012) and TNM stage (HR=1.64, p = 0.108). This was confirmed in the validation cohort, where L/MiT (HR = 1.71, p = 0.02) and tumor–node–metastasis (TNM) stage (HR = 1.66, p = 0.04) were shown to be independent adverse prognostic factors. Moreover, L/MiT stood out as the most prominent contributor in nomogram models constructed for survival prediction (area under the curve = 0.696 at 14 months), the dropout of which compromised prediction performance (area under the curve = 0.661 at 14 months). Furthermore, stratification analysis indicated that L/MiT tended preferentially to impact young and female patients (HR = 11.61, p < 0.0001, and HR = 9.55, p = 0.0008, respectively) in particular with early-stage and low-grade PDAC (HR = 2.37, p < 0.0001, and HR = 2.19, p < 0.0001, respectively), while TNM stage demonstrated little preference. CONCLUSION This was the first CIC profiling to be performed in PDAC, and is currently largest for human tumors. Subtyped CICs, as a valuable input to the traditional variables such as TNM stage, represent a novel type of prognostic factor. The formation of heterotypic L/MiT may be a surrogate for local immune evasion and predict poor survival, particularly in young female patients of resectable PDAC. Prior knowledge Novelty of study ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Key Research & Development Program of China (2016YFC1303303 to QS, 2018YFA0900804 to YZ, 2019YFA09003801 to QS), and the National Natural Science Foundation of China (81572799 to HH, 31671432 to QS, 31770975 to XW, 81972483 to MH). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Human tissue microarrays (TMA) and "clinical-type" gene chips (CTGCs)were purchased from The Outdo Biotech. Tissue sections were collected from 110 resectable PDAC patients who had received surgery at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), with the institutional research ethics committee reviewing and approving the research. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The raw/processed data required to reproduce these findings cannot be shared at this time as the data also forms part of an ongoing study.

目的:构建肿瘤细胞减灭程度(completeness of cytoreduction,CC)预测模型,为肿瘤细胞减灭术(cytoreductive surgery,CRS)加腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌腹膜转移(gastric cancer with peritoneal metastasis,GCPM)提供病例筛选方法.方法:比较完全CRS(complete CRS,CCRS)组和不完全CRS(incomplete CRS,ICRS)组患者基本临床病理特征和治疗参数,通过逻辑回归模型筛选CC独立预测因子,精准预测CCRS可能性.结果:125例患者纳入本研究,其中CC0组52例(41.6％),中位总生存期为30.0(95％CI:16.8～43.3)个月;CC1-3组73例,中位总生存期7.3(95％CI:5.7～8.8)个月,差异有统计学意义(P<0.001),而CC1、CC2和CC3组间中位总生存期差异无统计学意义(P>0.05).因此,CC0定义为CCRS组,CC1-3定义为ICRS组,构建并优化了以腹膜转移时相(OR=14,95％CI:2.0～97.9,P=0.008)、术前肿瘤标志物(OR=6.5,95％CI:2.1～37.8,P=0.037)和腹膜癌指数(OR=1.5,95％CI:1.3～1.8,P<0.001)预测ICRS的多因素回归模型和预测列线图,内部验证显示,ROC曲线下面积为0.985,列线图显示预测准确度、一致性良好.根据列线图结果将患者分为4个亚组,设定CCRS预测概率≥50％,同时性且术前肿瘤标志物正常组、同时性且术前肿瘤标志物异常组、异时性且术前肿瘤标志物正常组、异时性且术前肿瘤标志物异常组腹膜癌指数界值点分别为:≤16、≤12、≤10和≤5.结论:CCRS+HIPEC可延长部分经选择的GCPM患者生存期,以腹膜癌指数为核心,联合腹膜转移时相和术前肿瘤标志物的病例筛选策略,可有效选择高概率实现CCRS的患者接受CCRS+HIPEC治疗.

OBJECTIVE:The role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC. METHODS:From a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs). RESULTS:The median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8-43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8-8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7-10.2, months), CC-2 (5.6, 95%CI: 3.0-8.2, months) and CC-3 (6.5, 95%CI: 5.2-7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%. CONCLUSIONS:Only complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.

目的 评估肿瘤细胞减灭术(cytoreductive surgery,CRS)+腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗阑尾腺癌腹膜癌的疗效及安全性.方法 分析接受CRS+ HIPEC治疗的42例阑尾腺癌腹膜癌患者临床数据,研究指标为生存期、围手术期安全性及不良事件.结果 42例阑尾腺癌腹膜癌患者腹膜癌指数(peritoneal cancer index,PCI)1～39分,中位31分;肿瘤减灭程度(completeness of cytoreduction,CC)0 ～3分,中位2分.随访时间1 ～61个月(中位18.3个月),18例(42.9％)死亡,24例(57.1％)生存,中位生存时间为40.0个月(95％ CI:32.2 ～47.8个月),1、3和5年生存率分别为75.3％、52.8％和29.7％.CC≤1分和CC＞1分的患者中位生存时间分别为46.0和34.0个月(P =0.033).有和没有严重不良事件的患者中位生存时间分别为41.0和2.0个月(P =0.002).围手术期不良事件发生率为14.3％,切口感染裂开1例,肠吻合口瘘4例,急性心肌梗死1例.结论 CRS+ HIPEC治疗阑尾腺癌腹膜癌可行有效.