Peritoneal Cancer Index Score Research Articles

New metastasectomy criteria for peritoneal metastasis of hepatocellular carcinoma: A study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Peritoneal metastasis of hepatocellular carcinoma (HCC) is rare. We investigated patients who underwent peritoneal metastasectomy in a multicenter study in Japan. The study included 92 patients with HCC who underwent resection for peritoneal metastasis between January 2007 and December 2013. We investigated background and operative factors, as well as overall and recurrence-free survival rates. Patients were classified according to the extent of peritoneal metastasis using the peritoneal cancer index (PCI) and the completeness of cytoreduction (CC) scores to examine whether peritoneal metastasectomy contributed to survival. The mean maximum tumor size was 4.1cm. Forty patients (43.5%) had multiple peritoneal metastases. Peritoneal metastasectomy and hepatectomy were performed simultaneously in 48 patients (52.2%). Overall, the 5-year survival rate after resection was 36.0%, and the recurrence-free survival rate was 13.0%. Multivariate analysis revealed that PCI scores of ≤6+CC scores of 0 were an independent prognostic factor. The 5-year survival rate when these criteria were met was 43%, which was significantly better than that in those who did not meet these criteria (P<.001). Peritoneal metastasectomy of HCC appears to contribute to improved survival of patients with a PCI scores of ≤6, without remnant tumors.

The importance of primary tumor origin in gastrointestinal malignancies undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

BackgroundAppendiceal and colorectal cancers with peritoneal carcinomatosis (PC) can derive benefit from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, its role in gastric and small bowel malignancies remains undefined.MethodsWe retrospectively analyzed 251 gastrointestinal adenocarcinomas with PC which underwent CRS/HIPEC at our institution from 2007 to 2017. We compared outcomes of gastric, small bowel, appendiceal, and colorectal cohorts.ResultsThirty-one gastric, 8 small bowel, 91 appendiceal, and 121 colorectal cohorts were included. More gastric cancers (90%) received neoadjuvant chemotherapy than any other cohort, p = 0.002. Although colorectal had the lowest peritoneal cancer index (PCI) (9) and appendiceal the highest (16), all cohorts underwent similar rates of organ resection and complete cytoreduction. Length of stay (p = 0.005) and major perioperative morbidity (Clavien III/IV, p = 0.011) were significantly higher in gastric and small bowel. Median overall survival (OS, p < 0.001) was significantly shorter in gastric (13 months) and small bowel (9 months) than in appendiceal (33 months) and colorectal (42 months) cohorts. On multivariate analysis, complete cytoreduction and PCI score were significant predictors of OS, p < 0.05.ConclusionsPrimary tumor origin significantly affects outcomes after CRS/HIPEC for gastrointestinal malignancies. Though there was a survival benefit in appendiceal and colorectal, gastric and small bowel survival was comparable to systemic chemotherapy.

A multivariate analysis of the prognostic impact of tumor burden, surgical timing and complexity after complete cytoreduction for advanced ovarian cancer

ObjectiveTo assess the survival benefit of primary debulking surgery (PDS) compared to interval debulking surgery (IDS) after complete cytoreduction (CC-0) or cytoreduction to minimal residual disease (CC-1) in advanced ovarian cancer. Secondary objective was to evaluate the effect of tumor load and surgical complexity on patients' survival. MethodsA retrospective multicentric study was designed, including patients with IIIC-IV FIGO stage ovarian cancer who underwent PDS or IDS with CC-0 or CC-1 from January 2008 to December 2015 in four high-volume institutions. Patients were classified in three groups: PDS, IDS after 3–4 cycles of neoadjuvant chemotherapy (NACT), and IDS after 6 cycles. Disease-free survival (DFS) and overall survival (OS) were estimated. Univariable and multivariable analyses were conducted. ResultsWe included 549 patients, 175 (31.9%) underwent PDS, 224 (40.8%) had IDS after 3–4 cycles of NACT, and 150 (27.3%) underwent IDS after 6 cycles. Median DFS in PDS, IDS at 3–4 cycles and IDS at 6 cycles were 23.0 months (95%CI = [20.0–29.3]), 18.0 months (95%CI = [15.9–20.0]) and 17.1 months (95%CI = [15.0–20.9]), respectively; p < .001. Median OS were 84.0 months (95%CI = [68.3–111.0]), 50.7 months (95%CI = [44.6–59.5]) and 47.5 months (95%CI = [39.3–52.9]), respectively; p < .001. In multivariable analysis, high peritoneal cancer index score and NACT were negatively associated to DFS and OS. Surgical complexity and CC-1 were negatively associated to DFS. ConclusionPDS offered a survival gain of almost three years compared to IDS in patients with minimal or no residual disease after surgery. PDS should remain the standard of care for advanced ovarian cancer.

Impact of extent of disease on 1-year healthcare costs in patients who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: retrospective observational cohort study.

BackgroundThe goal of this retrospective observational study was to determine the impact of the extent of peritoneal disease on 1‐year healthcare costs in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). The extent of peritoneal disease, expressed by the Peritoneal Cancer Index (PCI), directly affects the complexity of CRS + HIPEC and ultimately survival outcomes. The impact of the PCI on treatment‐related healthcare costs remains unknown.MethodsData from patients with colorectal PM who underwent CRS + HIPEC between January 2012 and November 2017 were extracted retrospectively from an institutional database. Patients were divided into four subgroups with PCI scores ranging from 0 to 20. Treatment‐related costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the χ 2 test and Kruskal−Wallis H test.ResultsSeventy‐three patients were included (PCI 0–5, 22 patients; PCI 6–10, 19 patients; PCI 11–15, 17 patients; PCI 16–20, 15 patients). Median (i.q.r.) costs were significantly increased for the PCI 11–15 and PCI 16–20 groups (€51 029 (42 500–58 575) and €46 548 (35 194–60 533) respectively) compared with those for the PCI 0–5 and PCI 6–10 groups (€33 856 (25 293–42 235) and €39 013 (30 519–51 334) respectively) (P = 0·009).ConclusionTreatment‐related healthcare costs are significantly increased among patients with extensive tumour burden (PCI score 10 or above) who undergo CRS + HIPEC for the treatment of colorectal PM.

Comparison of the Peritoneal Cancer Index and Dutch region count as tools to stage patients with peritoneal metastases ofcolorectal cancer.

BackgroundExtent of peritoneal metastases (PM) is among the most powerful prognostic factors for survival after cytoreductive surgery (CRS). This study aimed to compare the Peritoneal Cancer Index (PCI) and the Dutch region count as tools for staging PM of colorectal cancer. The Dutch region count is a simpler classification that distinguishes seven rather than 13 abdominal regions. Presence or absence of PM is recorded.MethodsThis was a retrospective cohort study in two tertiary referral centres in the Netherlands. Consecutive patients with colorectal PM who were intentionally treated with CRS and subsequent hyperthermic intraperitoneal chemotherapy in 2016 and 2017 were included. The PCI and Dutch region count were both recorded during laparotomy. Correlation between scoring tools was calculated using Spearman's rank correlation coefficient. Diagnostic values were calculated for different cut‐off values of the PCI, alongside the Dutch region count. The correlation of both scores was determined for the exploration and validation cohorts separately.ResultsIn the exploration and validation cohorts, 73 and 85 patients respectively were included. Spearman's correlation coefficients of 0·897 and 0·961 were observed for continuous scores of the Dutch region count and PCI in the exploration and validation group respectively. A cut‐off value of 20 for the PCI score and 5 for the Dutch region count showed 91·9 and 94·5 per cent sensitivity, and 81·8 and 91·7 per cent specificity, respectively.ConclusionThe Dutch region count correlated well with the PCI score, and may help to simplify reporting of the extent of peritoneal disease.

Efficacy of intraperitoneally administered paclitaxel for colorectal cancer with peritoneal metastases.

Prognosis after peritoneal metastases in colorectal cancer is worse than that after lung or liver metastases. Previously, we demonstrated the safety of intraperitoneal (ip) administration of paclitaxel (PTX) combined with mFOLFOX6/CapeOX plus bevacizumab for colorectal cancer with peritoneal metastasis in a phase-I trial. Here, we evaluated the efficacy of this chemotherapy. We enrolled six patients with histologically confirmed peritoneal metastases secondary to colorectal cancer. PTX was administered through a peritoneal access port, in combination with oxaliplatin-based systematic chemotherapy. Response rate, progression-free survival, 1-year survival rate, frequency of improvement in peritoneal cancer index (PCI), and cytology in peritoneal lavage were evaluated. This study was registered in the University Hospital Medical Information Network Clinical Trial Registry on July 1, 2016 (UNIN000022924). Three patients received the mFOLFOX6-bevacizumab regimen, whereas the other three received the CapeOX-bevacizumab regimen. The response rate was 25%. PCI score improved in 50% of the cases. Peritoneal lavage cytology that was positive in five patients before initiating the chemotherapy turned negative during chemotherapy in all patients. One-year survival rate was 100%, progression-free survival was 8.8months (range, 6.8-12months), and median survival time was 29.3months. The ip administration of PTX with systemic chemotherapy can potentially control peritoneal metastases in colorectal cancer.

The Peritoneal Cancer Index is a Strong Predictor of Incomplete Cytoreductive Surgery in Ovarian Cancer

BackgroundExtent of tumor load is an important factor in the selection of ovarian cancer patients for cytoreductive surgery (CRS). The Peritoneal Cancer Index (PCI) gives exact information on tumor load but still is not standard in ovarian cancer surgery. The aim of this study was to find a PCI cutoff for incomplete CRS. The secondary aims were to identify reasons for open-close surgery and to compare surgical complications in relation to tumor burden.MethodsThe study included 167 women with stage III or IV ovarian cancer scheduled for CRS. Possible predictors of incomplete surgery were evaluated with receiver operator curves, and a PCI cutoff was identified. Surgical complications were analyzed by one-way analysis of variance and Chi square tests.ResultsThe median PCI score for all the patients was 22 (range 3–37) but 33 (range 25–37) for the patients with incomplete surgery (n = 19). The PCI predicted incomplete CRS, with an area under the curve of 0.94 (95% confidence interval [CI], 0.91–0.98). Complete CRS was obtained for 67.2% of the patients with a PCI higher than 24, who experienced an increased rate of complications (p = 0.008). Overall major complications were found in 16.9% of the cases. Only 28.6% of the patients with a PCI higher than 33 achieved complete CRS. The reason for open-close surgery (n = 14) was massive carcinomatosis on the small bowel in all cases.ConclusionThe study found PCI to be an excellent predictor of incomplete CRS. Due to a lower surgical success rate, the authors suggest that neoadjuvant chemotherapy could be considered if the PCI is higher than 24. Preoperative radiologic assessment should focus on total tumor burden and not necessarily on specific regions.

Clinical evaluation of tumor-stroma ratio in pseudomyxoma peritonei from the appendix

To evaluate the effect of tumor-stroma ratio (TSR) on disease progression and prognosis of pseudomyxoma peritonei (PMP) from the appendix. The study included 30 PMP patients with complete individual patient data, who underwent cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in Beijing Shijitan Hospital. Image-Pro Plus was used to quantitatively analyze the proportion of tumor and stromal areas in hematoxylin-eosin staining pathological images, from which TSR was derived. Correlation studies were conducted to evaluate the relationships between TSR and clinicopathological features, immunohistochemical characteristics, and prognosis of PMP. Among 30 PMP patients, there were 16 males (53.3%) and 14 females (46.7%), with the mean age of (54.9±2.3) years. There were 15 cases (50.0%) of low-grade mucinous carcinoma peritonei (LMCP) and high-grade mucinous carcinoma peritonei (HMCP), respectively, with vascular tumor emboli occurring in 4 cases (13.3%), nerve invasion occurring in 3 cases (10.0%), and lymphatic metastasis occurring in 4 cases (13.3%). The median peritoneal cancer index (PCI) score was 36 (range: 3-39). The median TSR was 8% (range: 2%-24%), with TSR≤10% in 19 cases (63.3%) and TSR>10% in 11 cases (36.7%). Immunohistochemistry showed that 16 cases (53.3%) had Ki67 label index ≤ 50% and 14 cases (46.7%) > 50%. The mutation rate of p53 was 56.7% and the loss rate of MMR protein was 11.8%. In addition, the expression rates of MUC2, MUC5AC, CDX2, CK7, and CK20 were 66.7%, 100.0%, 82.6%, 56.0%, and 92.3%, respectively. There were significant correlations between TSR and histopathological types, nerve invasion, Ki67 label index, and p53 mutation (P<0.05 for all). At the end of the last follow-up, 21 patients (70.0%) died and 9 patients (30.0%) survived, including 6 patients survived with tumor. The median overall survival (OS) was 12.7 months (95%CI: 10.4-11.5 months), and the 1-, 2-, and 3-year survival rates were 60.5%, 32.3%, and 27.7%, respectively. The median OS was 19.4 months (95%CI: 3.0-35.9 months) in the TSR≤10% group, versus 12.6 months (95%CI: 0.7-24.5 months) in the TSR>10% group (χ2=3.996, P=0.046). TSR is correlated with histopathological types, tumor proliferation, invasion behaviors and prognosis of PMP, thus could be a new prognostic indicator for PMP.

Impact of Neoadjuvant Chemotherapy on the Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Multi-Institutional Retrospective Review.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

Establishment and characterization of patient derived xenograft model of malignant peritoneal mesothelioma in nude mice

Objective: To establish patient derived xenograft (PDX) model of malignant peritoneal mesothelioma (MPM), and to identify the key characteristics of tumor biology of the model, so as to provide an experiment platform for studying the pathologic mechanisms and new therapeutic strategies for MPM. Methods: Surgically excised MPM tumor tissues were inoculated subcutaneously in BALB/c-nu/nu mice for 3 stable passages. In the 4th passage, the subcutaneous tumors were harvested under aseptic conditions, cleaned and made into MPM tumor cell homogenate. Four nude mice (two males and two females) were selected and one male and one female nude mouse were inoculated in the abdominal cavity at the dose of 100 μL, others were inoculated at a dose of 200 μL. The PDX model of MPM was established. The changes of body mass in nude mice were measured regularly, the extent of abdominal and pelvic tumors was judged by experimental peritoneal cancer index (ePCI) score, and the pathologic characteristics of tumors were analyzed. Results: The subcutaneous and abdominal animal models of MPM were successfully established. The subcutaneous tumor model grew into tumor on the 20th day, followed by a slow growth stage between the 20th and 29th day, then a rapid growth stage between the 30th and 57th day. According to the dose of tumor cells (100, 200 μL) and timing (14th and 69th days after grafting), the abdominal tumor model successfully simulated the early and late clinical stages of MPM. The HE staining results of the MPM nude mice model showed that the tumor was epithelial mesothelioma and invaded most of the organs, including liver, spleen, pancreas, mesentery. Immunohistochemical staining for calretinin, cytokeratin 5/6, WT1 and Ki-67 were positive. Whole-genome exon sequencing identified 26 and 36 high frequency gene mutations in tumors derived from the PDX model and clinical sample from patients, including 21 common gene mutations. Conclusions: The PDX model of MPM is established. The model is characterized by highly malignant tumor with rapid growth and high invasiveness.

Hyperthermic intraperitoneal chemotherapy post cytoreductive surgery in management of peritoneal carcinomatosis of colorectal primaries: Tertiary center experience.

28 Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) in addition to Cytoreductive surgery (CRS) has survival benefit observed in management of Peritoneal Carcinomatosis (PC) from Colo-rectal cancer (CRC)origin. We report the outcomes and prognostic factors of patients with CRC, who presented with PC and underwent CRS and HIPEC at King Faisal Specialist Hospital &amp; Research Center, Riyadh, Saudi Arabia. Methods: Patients presented with PC from CRC origin and underwent CRS and HIPEC; from February 2009 to September 2015 were recruited. Results: 52 patients identified. A total of 55 CRS procedures were performed, where 3 patients underwent repeated CRS and HIPEC for tumor recurrence. All except 3 used mitomycin-C for HIPEC, the remaining received either melphalan (2 patients) or cisplatin plus mitomycin-C regimen (1 patient). Melphalan used for patients who underwent repeated HIPEC as 2nd line chemotherapeutic agent. Intraoperative Radiation therapy performed in 5 patients with tumor invading the surrounding structures, where performing a safe or complete resection was either technically difficult or carried high risk. Complication assessment by Clavien-Dindo score, 62 % grade (I-II), while 31% had grade (3–4). Two patients (3.6%) died postoperatively; both from sepsis. Respiratory complications were the most commonly encountered morbidities. The 5-year overall survival(OS) was 50% with disease free survival (DFS) 29.5%. Univariate analysis showed poor OS and DFS encountered in; Signet-ring tumors (p &lt; 0.0001) for both, peritoneal cancer index (PCI) ≥ 6 (p &lt; 0.0009) for both, completeness of cytoreduction(CC) score &gt;1 (p &lt; 0.0001) for both, and high 3-month postoperative carcinoembryonic antigen value (p &lt;0.0001) for both. In multivariate analysis; DFS was significant for (PCI) ≥ 6 (p &lt; 0.0131) and (CC) score &gt;1 (p &lt; 0.0031) while PCI &gt; 6 was the only significant factor (p &lt; 0.0030) for OS. Conclusions: Addition of HIPEC to CRS was safe, and improved survival in patient with peritoneal Carcinomatosis of colo-rectal origin. PCI and CC score are prognostic factors of survival, signet-ring subtype may not benefit of this procedure.

5-hydroxymethylation signatures in plasma circulating cell-free DNA as markers for appendiceal and colorectal peritoneal metastasis.

195 Background: Noninvasive tests for peritoneal metastasis (PM) detection lack sensitivity. Genome-wide mapping of 5-hydroxymethylcytosine (5hmC) on nanogram quantities of peripheral plasma circulating cell-free DNA (PcfDNA) was previously shown to differentiate non-metastatic colorectal cancer from healthy subjects. We aimed to examine if patients with colorectal cancer (CRC), high grade appendiceal cancer (HGA) or low grade appendiceal cancer (LGA) with PM have distinct signatures of 5hmC in PcfDNA compared to each other and to patients matched for tumors without PM. Methods: We analyzed plasma samples from a prospectively collected tissue bank. To correlate 5hmC signatures with intraoperative findings, only patients who underwent abdominal surgery in proximity to plasma collection were selected. Key steps of PcfDNA processing included extraction from plasma, nano-hmC-Seal chemical labeling and enrichment of 5hmC-modified fragments, next-generation sequencing, and mapping to the reference human genome. DESeq2 R package was finally used to compare relative 5hmC enrichment and detect distinct 5hmC signatures according to disease histology and PM presence. Results: Plasma samples were collected between 11/2016 – 3/2019 from 46 patients with CRC (n = 21), HGA (n = 17) and LGA (n = 8). Of those, 32 (70%) had PM based on intraoperative findings (median peritoneal cancer index score = 15, range 2-39) and 14 did not have PM. Most samples (91%) were collected on the same day as surgery. An average of 24 million paired-end reads were sequenced for each sample. Four samples (8.7%) were excluded from the analysis due to low sequencing coverage or high duplication level. Unique 5hmC enrichment patterns were found to discriminate with p &lt; 0.05 between CRC PM and HGA PM (n = 616 differentially hydroxymethylated genes (DHMGs)), CRC/HGA PM and LGA PM (n = 1074 DHMGs), and CRC/HGA PM and CRC/HGA patients without PM (n = 1576 DHMGs). Conclusions: Distinct signatures of 5hmC in PcfDNA could differentiate patients with CRC/HGA/LGA PM from each other and from patients with similar tumor histologies without PM. Thus 5hmC signatures in PcfDNA might potentially serve as a sensitive marker of occult PM.

The Accuracy of The Clinical Peritoneal Cancer Index in Patients with Peritoneal Carcinomatosis of Colorectal Cancer

Background: The Peritoneal Cancer Index (PCI) and completeness of cytoreduction are important prognostic factors in patients with peritoneal carcinomatosis from colorectal cancer, undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The PCI is determined during laparotomy by an experienced surgeon before the decision is made to ‘do’ or ‘do not’ proceed with CRS-HIPEC. The aim of this study is to determine the accuracy of the clinical PCI score (cPCI), by comparing the cPCI with the pathological PCI (pPCI) score.

Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion: PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

Establishment of patient-derived xenograft model of peritoneal mucinous carcinomatosis with signet ring cells and in vivo study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil.

BackgroundPseudomyxoma peritonei (PMP) is an indolent malignancy and insensitive to systemic chemotherapy. The authors established patient‐derived xenograft (PDX) model of PMP, and evaluated the efficacy and toxicity of intraperitoneal (i.p.) administration of 5‐fluorouracil (5‐FU) in this model.MethodsHuman PMP sample was collected to establish subcutaneous (s.c.) and i.p. model. In vivo study of i.p. injection of 5‐FU was performed in i.p. model, with experimental peritoneal cancer index (ePCI) score and pathological examinations for evaluating the efficacy and toxicity.ResultsBoth s.c. and i.p. models were constructed. The average passage interval of s.c. model was 44.2 ± 5.2 days, and the i.p. model was characterized by disseminated solid tumor nodules in abdominal‐pelvic cavity. Both models were diagnosed as peritoneal mucinous carcinomatosis with signet ring cells (PMCA‐S). Immunohistochemical characteristics was similar to human. GNAS mutation was detected in both model and patient. In the in vivo study, average ePCI of treatment group was lower than control and vehicle group (P = .004). Histopathology revealed obvious tumor necrosis in treatment group, and decreased Ki67 positive rate (P = .010). In toxicity study, 5‐FU significantly influenced body weight (P = .010) and 1 animal from treatment group died on day 14. Congestive splenomegaly was observed (88.9%). Hepatotoxicity presented as acidophilic body (55.6%), cholestasis (100%), bile canaliculus hyperplasia and obstruction (22.2%), and lymphocyte accumulation (77.8%).ConclusionsPDX model of PMCA‐S was established successfully, and i.p. 5‐FU could inhibit tumor proliferation and progression, with decreased Ki67 positive rate and ePCI score. Hepatotoxicity was the main side effect.

Concomitant intraperitoneal and systemic chemotherapy for extensive peritoneal metastases of colorectal origin: protocol of the multicentre, open-label, phase I, dose-escalation INTERACT trial

IntroductionCytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases of colorectal origin with a low/moderate abdominal disease load. In case of a...

Pre-operative serum CA125, peritoneal cancer index and intra-operative mapping score as predictors of surgical results in primary epithelial ovarian cancer

ObjectivePrediction of post-operative residual disease after ovarian cancer cytoreductive surgery remains a topic of interest to gynecologic oncologists. The aim of this study was to explore the correlation between serum...

Value of preoperative ultrasound in evaluating the peritoneal cancer index of pseudomyxoma peritonei

PurposeThis study aimed to explore the value of preoperative ultrasonography (US) in evaluating the peritoneal cancer index (PCI) of pseudomyxoma peritonei (PMP).MethodsAn ultrasound examination was performed on 59 patients with PMP before surgery, and the ultrasound PCI was evaluated. The accuracy of ultrasound PCI score was evaluated with the surgical PCI score as the gold standard.ResultsThe preoperative ultrasound PCI was compared with the surgical PCI. The Spearman correlation coefficient of the total PCI score was 0.608 (P < 0.05). The difference in the Spearman correlation coefficient between the preoperative ultrasound PCI and the surgical PCI in areas 0–7 was statistically significant. (1) Among them, the total score and the correlation between 0–3 and 6 were higher. (2) Compared with the surgical PCI, overestimation (> 20%) was concentrated mainly in areas 2 and 4–8 for 2 points, and underestimation (< 20%) was concentrated mainly in areas 1, 3, 4, and 8 for 3 points. (3) The sensitivity and specificity of preoperative ultrasound for predicting the presence or absence of lesions were 85.7% and 50.0%, respectively. The sensitivity of LS 1, LS 2, and LS 3 was 31.7%, 48.2%, and 71.0%, respectively, and the specificity was 44.8%, 55.3%, and 58.8%, respectively.ConclusionThe ultrasound examination can be used to score the preoperative PCI, judge the severity, and predict the prognosis in patients with PMP.

Factors affecting R0 resection of colorectal cancer with synchronous peritoneal metastases: a multicenter prospective observational study by the Japanese Society for Cancer of the Colon and Rectum.

In Japan, R0 resection has been recommended for colorectal cancer patients with peritoneal metastases confined to the adjacent peritoneum and those with a few metastases to the distant peritoneum. R0 resection for M1c disease has drawn attention in Western countries and is currently considered an acceptable therapeutic option in the US National Comprehensive Cancer Network guidelines. However, clinical factors that affect the choice of R0 resection are unknown. This multicenter, prospective, observational study was conducted by the Japanese Society for Cancer of the Colon and Rectum. Colorectal cancer patients with synchronous peritoneal metastases were enrolled at 28 institutions in Japan from October 2012 to December 2016. To determine factors affecting R0 resection and R1 resection with intended R0 resection, stepwise logistic regression analyses were performed on clinical factors including age, sex, performance status (PS), body mass index, peritoneal cancer index (PCI) score, presence of ascites, presence of distant metastases, and primary tumor site. R0/R1 resection was performed in 36 (31/5; 25%) of 146 patients. No distant metastases [odds ratio (OR) 52.9; 95% confidence interval (CI) 13.3-210.1; p < 0.0001], low PCI score (1-6) (OR 20.0; 95% CI 4.8-83.4; p < 0.0001), and high PS (0) (OR 2.40; 95% CI 0.66-8.68; p = 0.18) were independent factors affecting R0/R1 resection. PCI score and PS were also independent factors affecting R0/R1 resection in M1c patients without non-peritoneal distant metastases (n = 59). Distant metastases, PCI score, and PS are three factors which affect R0 resection for M1c disease.

Experimental study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil to treat PDX model of pseudomyxoma peritonei

Objective To evaluate the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil (5-Fu) in patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP). Methods One PMP tumor from surgery was used to establish PMP PDX models, which were equally randomized into control (no treatment), vehicle (normal saline, 0.2 ml) and treatment (5-Fu, 50 mg/kg, 0.2 ml) groups. Experimental peritoneal cancer index (ePCI) score, body weight, and pathological examination were performed to evaluate the efficacy and toxicity. Results PDX models replicating human PMP were established and diagnosed as high grade mucinous carcinoma peritonei with signet ring cells. Average ePCI score of treatment group was significantly lower than control and vehicle groups [(0.9±1.2) points vs. (3.6±1.7) points vs. (2.7±1.1) points, F=9.253, P<0.01]. Histopathological study revealed obvious tumor necrosis and reduced signet ring cells in the treatment group. The Ki-67 label index of treatment group was significantly lower than control group and vehicle group [(57.3±15.1)% vs. (72.2±15.1)% vs. (70.0±14.0)%, F=4.923, P<0.05]. The body weight of treatment group was significantly lower than control group and vehicle group [(19.7±2.8) g vs. (22.7±1.8) g vs. (21.9±1.7) g, F=4.654, P<0.05]. Major toxicities in the treatment group were animal death (10.0%), congestive splenomegaly (88.9%), lymphocyte accumulation (77.8%), bile canaliculus hyperplasia and obstruction (22.2%), cholestasis (100.0%), and acidophilic body (55.6%) in the liver. Conclusion In the PDX model of human PMP, intraperitoneal injection of 5-Fu could inhibit tumor proliferation and progression, with lowered ePCI score and reduced Ki-67, and toxicity was mainly on liver. Key words: Pseudomyxoma peritonei; PDX model; 5-Fluorouracil; Intraperitoneal injection; Organ toxicity