Treatment Of Peritoneal Metastases Research Articles

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.

The structural effect of high intensity ultrasound on peritoneal tissue: a potential vehicle for targeting peritoneal metastases

BackgroundHigh-intensity ultrasound (HIUS) has been increasingly investigated as a possible tool in the treatment of multiple tumor entities. However, there is only little knowledge on the effect of HIUS on the peritoneum. This preliminary study aims to investigate HIUS’ potential for altering the peritoneal surface and potentially improving current treatments for peritoneal metastases. For this purpose, HIUS’ qualitative and quantitative structural effects on the peritoneal tissue were analyzed by means of light, fluorescence and electron microscopy.MethodsProportional sections were cut from the fresh postmortem swine peritoneum. Peritoneal surfaces were covered with a 6 mm thick liquid film of 0.9% NaCl. HIUS was applied in all tissue samples for 0 (control), 30, 60, 120 and 300 s. Peritoneal tissues were analyzed using light-, fluorescence and electron microscopy to detect possible structural changes within the tissues.ResultsFollowing HIUS, a superficial disruption of peritoneal tissue was visible in light microscopy, which amplified with increased time of HIUS’ application. Fluorescence microscopy showed both peritoneal and subperitoneal disruption with tissue gaps. Electron microscopy revealed structural filamentation of the peritoneal surface.ConclusionOur data indicate that HIUS causes a wide range of effects on the peritoneal tissue, including the formation of small ruptures in both peritoneal and subperitoneal tissues. However, according to our findings, these disruptions are limited to a microscopical level. Further studies are required to evaluate whether HIUS application can benefit current therapeutic regimens on peritoneal metastases and possibly enhance the efficacy of intraperitoneal chemotherapy.

Hepatic resection and blood transfusion increase morbidity after cytoreductive surgery and HIPEC for colorectal carcinomatosis.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective but complex treatment for peritoneal metastasis (PM). Our objective was to identify risk factors for postoperative morbidity and mortality following CRS-HIPEC. Retrospective study of prospectively collected data of patients undergoing CRS-HIPEC for PM arises from colorectal cancer between January 2008 and December 2017. Perioperative variables were correlated with morbidity outcomes using a logistic regression model. Sixty-seven patients underwent CRS-HIPEC, and overall morbidity and mortality were 31.3% and 4.5% respectively. Major morbidity rate was 19.4%; 7.5% of patients were re-operated. Intraoperative blood transfusion (p = 0.01), liver resection (p < 0.01), and intestinal anastomosis (p < 0.01) were associated with a higher morbidity in univariate analysis. A multivariate analysis identified blood transfusion and liver resection as independent risk factors (OR 3.66, IC 1.13-16.54; OR 4.33, IC 1.17-11.46, respectively). Extension of visceral resection did not correlate with morbidity. Patients with lymph-node infiltration had a higher major complication rate (p = 0.01). CRS-HIPEC is a feasible treatment for colorectal PM with an acceptable morbi-mortality rate in experienced centers. In our study, digestive anastomosis, perioperative blood transfusion, hepatic resection, and lymph-node infiltration were associated with higher morbidity rates.

Tumor Microenvironment-Activated NIR-II Nanotheranostic System for Precise Diagnosis and Treatment of Peritoneal Metastasis.

Activatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side-effects. Herein, a tumor microenvironment (TME)-activated NIR-II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self-assembling the peptide Fmoc-His, mercaptopropionic-functionalized Ag2 S quantum dots (MPA-Ag2 S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR-II fluorescence "off" state, because of Ag2 S QDs-A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc-His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag2 S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME-activated theranostic strategy holds great promise for future clinical applications.

Tumor Microenvironment‐Activated NIR‐II Nanotheranostic System for Precise Diagnosis and Treatment of Peritoneal Metastasis

AbstractActivatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side‐effects. Herein, a tumor microenvironment (TME)‐activated NIR‐II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self‐assembling the peptide Fmoc‐His, mercaptopropionic‐functionalized Ag2S quantum dots (MPA‐Ag2S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR‐II fluorescence “off” state, because of Ag2S QDs‐A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc‐His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag2S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME‐activated theranostic strategy holds great promise for future clinical applications.

Electrostatic Precipitation Is a Valuable Adjunct to Pressurized Intraperitoneal Aerosol Chemotherapy: An in Vitro Study

BACKGROUND: Peritoneal metastasis (PM) is a frequent manifestation of gastro-intestinal and gynaecological cancer. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was recently introduced for the treatment of irresectable PM, with promising anticancer activity and adequate tolerance. Adding electrostatic force (i.e. 7.5 – 9.5 kV; a current of ≤ 10 µA) to aerosolized particles could further enhance the pharmacologic properties of PIPAC. This procedure is termed electrostatic precipitation PIPAC or ePIPAC. This in vitro study investigated if ePIPAC could lead to a more homogeneous distribution of the drug and an increased penetration depth, enhancing the efficacy of PIPAC. MATERIALS AND METHODS: Black ink was nebulized (PIPAC n=6; ePIPAC n=6) in an in vitro box model containing fresh swine omentum on four different locations: on the bottom of the box (A), under a bilaterally open plastic tunnel (B), on the side wall of the box (C) and on the top of the box (D). The proportion (%) black ink in each specimen was macroscopically measured by ImageJ. The specimens were then embedded and cryosections (20 µm) were made. Each cryosection was scored by three independent observers for the amount of ink visible on the tissue surface using a light microscope: 0 = no ink visible; 0.5 = hardly visible line; 1 = clear line visible. To evaluate the penetration depth after PIPAC and ePIPAC, carboxylate-modified red fluorescent microspheres of 0.1 µm were nebulized (PIPAC n=6; ePIPAC n=6) in the in vitro box. The penetration depth of the microspheres was measured by confocal fluorescence imaging. RESULTS: No significant differences of the stained proportion of the specimens were found at location A (99 ± 1% vs. 98 ± 2%) and B (98 ± 2% vs. 96 ± 4%) in PIPAC and ePIPAC, respectively. Strikingly, a significant (p=0.015) increase was found in location C (68 ± 27% vs. 93 ± 9%) and D (23 ± 35% vs. 84 ± 30%) after ePIPAC, indicating a more homogeneous distribution pattern. These findings were in accordance with the mean cryosection scores: histological ink staining did not differ on location A (0.89 ± 0.17 vs. 1 ± 0.00) and B (0.89 ± 0.20 vs. 0.94 ± 0.09) after PIPAC and ePIPAC, respectively. However, specimens on locations C (0.39 ± 0.33 vs. 0.94 ± 0.09; p=0.0065) and D (0.22 ± 0.36 vs. 0.78 ± 0.20; p=0.022) were significantly more stained after ePIPAC than after PIPAC. Results regarding the penetration depth of the fluorescently labelled microspheres will also be presented. CONCLUSIONS: The addition of electrostatic precipitation to PIPAC significantly enhances aerosol distribution pattern in an in vitro box model. Consequently, ePIPAC may allow more homogeneous and efficient drug uptake, and improve the management of irresectable PM. At the same time, ePIPAC may allow to use a lower drug dose, and lead to less side effects.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study.

ObjectiveSystemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.MethodsThis retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.ResultsOf 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58−0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%−14.8%) and 18.4% (95% CI, 12.3%−24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months. ConclusionsCompared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.

Rationality of performing hyperthermic intraperitoneal chemotherapy 5-8 weeks after primary tumor resection for patients with locally advanced colorectal cancer-based on COLOPEC

Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the "Lancet Gastroenterol Hepatol" (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m(2)) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.

Albumin-based cancer therapeutics for intraperitoneal drug delivery: a review

Albumin is a remarkable carrier protein with multiple cellular receptor and ligand binding sites, which are able to bind and transport numerous endogenous and exogenous compounds. The development of albumin-bound drugs is gaining increased importance in the targeted delivery of cancer therapy. Intraperitoneal (IP) drug delivery represents an attractive strategy for the local treatment of peritoneal metastasis (PM). PM is characterized by the presence of widespread metastatic tumor nodules on the peritoneum, mostly originating from gastro-intestinal or gynaecological cancers. Albumin as a carrier for chemotherapy holds considerable promise for IP delivery in patients with PM. Data from recent (pre)clinical trials suggest that IP albumin-bound chemotherapy may result in superior efficacy in the treatment of PM compared to standard chemotherapy formulations. Here, we review the evidence on albumin-bound chemotherapy with a focus on IP administration and its efficacy in PM.

Exosomal microRNA in peritoneal fluid as a biomarker of peritoneal metastases from gastric cancer.

AimPeritoneal metastases (PM) frequently occur in patients with gastric cancer and result in a poor prognosis. Exosomes play pivotal roles in tumor metastasis through the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify novel biomarkers to reflect tumor burden in the peritoneum.MethodsExosomes were isolated from peritoneal fluids of patients of gastric cancer with macroscopic (P1) or microscopic (P0CY1) peritoneal metastasis (PM) and comprehensive miRNA expression analysis was carried out. Expressions of candidate miRNAs were then validated in all 58 samples using TaqMan Advanced miRNA Assays.ResultsIn initial screening, we carried out comprehensive analysis of exosomal miRNA using peritoneal fluids from 11 and 14 patients with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis showed that four miRNAs (miR‐21‐5p, miR‐92a‐3p, miR‐223‐3p, and miR‐342‐3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index. In contrast, miR‐29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR‐29 at gastrectomy tended to be lower in six patients with peritoneal recurrence with significant differences in miR‐29b‐3p (P = .012).ConclusionExpression pattern of miRNAs in peritoneal exosomes well reflects the tumor burden in the peritoneal cavity and could be a useful biomarker in the treatment of PM.

Colorectal Peritoneal Metastases Treated by Perioperative Systemic Chemotherapy and Cytoreductive Surgery With or Without Mitomycin C-Based HIPEC: A Comparative Study Using the Peritoneal Surface Disease Severity Score (PSDSS).

The Prodige-7 trial has questioned the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases from colorectal cancer (CRC-PM). We compared a prospectively collected group of 48 patients undergoing oxaliplatin/irinotecan-based perioperative systemic chemotherapy (s-CT) with targeted agents, and cytoreductive surgery (CRS) (no-HIPEC group) with 48 controls undergoing the same perioperative s-CT and CRS/HIPEC (HIPEC group). Patients were matched (1:1) according to the Peritoneal Surface Disease Severity Score, completeness of cytoreduction, history of extraperitoneal disease (EPD), and Peritoneal Cancer Index. The groups were comparable, except for a higher number of patients in the HIPEC group with World Health Organization performance status 0, pN2 stage primary tumor, and treated with preoperative s-CT. Forty-one patients in the no-HIPEC group and 43 patients in the HIPEC group had optimal comprehensive treatment (P = 0.759), defined as complete cytoreduction of PM and margin-negative EPD resection. Median follow-up was 31.6months in the no-HIPEC group and 39.9months in the HIPEC group. Median overall survival was 39.3months in the no-HIPEC group and 34.8months in the HIPEC group (P = 0.702). In the two groups, severe morbidity occurred in 14 (29.2%) and 13 (27.1%) patients, respectively (P = 1.000), with no operative deaths. On multivariate analysis, left-sided primary and curative treatment independently correlated with better survival while HIPEC did not (hazard ratio 0.73; 95% confidence interval 0.47-1.15; P = 0.178). Our results confirmed that, in selected patients, perioperative s-CT and surgical treatment of CRC-PM resulted in unexpectedly high survival rates. Mitomycin C-based HIPEC did not increase morbidity but did not impact prognosis.

Research progress in cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for peritoneal metastasis of colorectal cancer

Colorectal cancer peritoneal metastasis has traditionally been considered as one of the end-stage manifestations. Recently, cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy achieved promising results in prolonging survival of patients and reducing tumor recurrences. Many guidelines suggested that the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is an acceptable treatment for peritoneal metastasis. This article highlighted the treatment method, reviewed the latest evidence in treatment of colorectal cancer peritoneal metastasis and explored future direction. Key words: Colorectal neoplasms; Colorectal cancer; Peritoneal metastasis; Hyperthermic intraperitoneal chemotherapy; Cytoreductive surgery

Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC)

IntroductionRepetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However,...

Introduction of a variable electrostatic field for targeted drug application following intraperitoneal aerosol chemotherapy (PIPAC).

e14211 Background: In the treatment of Peritoneal Metastasis, the delivery of pressurized chemo-aerosols into the capnoperitoneum has been reported to show superior qualities to the application of conventional liquid chemotherapy. However, there is little basic knowledge on how aerosol particle motion within the abdominal cavity may be influenced and directed by means of an electrostatic field. This study aims to investigate aerosol motion within the abdominal cavity using an ex-vivo model. Material and Methods: All experiments were performed in an ex-vivo box as well as on postmortem swine abdomen, both established ex-vivo PIPAC models previously introduced by our research team. Extra-abdominally created, unipolar charged aerosols are introduced to the abdominal cavity. A modulated electrostatic field within the abdominal cavity is established to examine aerosol particle collision via fluorescence microscopy and photography. Results: Aerosol particle collision was observed on the peritoneum in the varying electric field. Preliminary data suggests that tissue penetration rates change with a varying electric field (p &lt; 0.05). Drug distribution pattern showed a significant improvement with a varying electric field vs. without (p &lt; 0.05). Conclusions: Our data suggest that extra-abdominally created, highly drug concentrated aerosol particles have the capacity to achieve high drug penetration rates in the peritoneum. The addition of a varying electric field enhances particle collision as well as significantly improves drug distribution patterns. Further studies are required to investigate the in-vivo safety and efficacy of a varying electric field and the significance of extra-abdominally created chemo-aerosols with regards to possible clinical applications.

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Backgroundpressurized intraperitoneal aerosol chemotherapy (PIPAC), with or without electrostatic precipitation (ePIPAC), was recently introduced in the treatment of peritoneal metastases (PM) from ovarian cancer (OC). Preliminary clinical data are promising, but several methodological issues as well the anticancer efficacy of PIPAC remain unaddressed. Here, we propose a rat ePIPAC model that allows to study these issues in a clinically relevant, reproducible, and high throughput model.Methodslaparoscopy and PIPAC were established in healthy Wistar rats. Aerosol properties were measured using laser diffraction spectrometry based granulometric analyses. Electrostatic precipitation was accomplished using a commercially available generator (Ultravision™). A xenograft model of ovarian PM was created in athymic rats using intraperitoneal (IP) injection of SKOV-3 luciferase positive cells. Tumor growth was monitored weekly by in vivo bioluminescence imaging.ResultsPIPAC and electrostatic precipitation were well tolerated using a capnoperitoneum of 8 mmHg. All rats survived the (e)PIPAC procedure and no gas or aerosol leakage was observed over the entire procedure. With an injection pressure of 20 bar, granulometry showed a mean droplet diameter (D(v,0.5)) of 47 μm with a flow rate of 0.5 mL/s, and a significantly lower diameter (30 μm) when a flow rate of 0.8 mL/s was used. Experiments using IP injection of SKOV-3 luciferase positive cells showed that after IP injection of 20 × 106 cells, miliary PM was observed in all animals. PIPAC was feasible and well supported in these tumor bearing animals.Conclusionswe propose a reproducible and efficient rodent model to study PIPAC and ePIPAC in OC xenografts with widespread PM. This model allows to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPAC treatment.

Laparoscopy in the diagnosis and treatment of peritoneal metastases

Over two decades the benefits of laparoscopy in the diagnosis and treatment of peritoneal metastases has been studied. Increasing utilization of this surgical tool has occurred with efficacy and safety demonstrated. The cancer surgery literature concerning the problem that peritoneal metastases presents, its adverse outcomes, and benefits of treatment were reviewed for patients with gastrointestinal malignancy. A major indication for laparoscopy is to determine the presence versus absence of peritoneal metastases. This may be especially important when planning treatments for gastric cancer. Repeated laparoscopy is used to monitor the efficacy of multiple cycles of intraperitoneal chemotherapy. Therapeutic laparoscopy involves the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with primary cancer who are at risk for subsequent peritoneal metastases or in those patients with peritoneal metastases diagnosed in follow-up. There are multiple applications of laparoscopy in patients with peritoneal metastases is indicated in many clinical situations as reviewed in this manuscript. Oftentimes, radiologic and laparoscopic assessments can be used to compliment each other.

Laparoscopy in the diagnosis and treatment of peritoneal metastases

Over two decades the benefits of laparoscopy in the diagnosis and treatment of peritoneal metastases has been studied. Increasing utilization of this surgical tool has occurred with efficacy and safety demonstrated. The cancer surgery literature concerning the problem that peritoneal metastases presents, its adverse outcomes, and benefits of treatment were reviewed for patients with gastrointestinal malignancy. A major indication for laparoscopy is to determine the presence versus absence of peritoneal metastases. This may be especially important when planning treatments for gastric cancer. Repeated laparoscopy is used to monitor the efficacy of multiple cycles of intraperitoneal chemotherapy. Therapeutic laparoscopy involves the administration of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with primary cancer who are at risk for subsequent peritoneal metastases or in those patients with peritoneal metastases diagnosed in follow-up. There are multiple applications of laparoscopy in patients with peritoneal metastases is indicated in many clinical situations as reviewed in this manuscript. Oftentimes, radiologic and laparoscopic assessments can be used to compliment each other.

History of Peritoneal Surface Malignancy Treatment in Japan.

In this review, Japanese experience of cytoreductive surgery and perioperative chemotherapy is described. The new concept of peritoneal metastasis (PM) type, i.e., trans-mesothelial, trans-lymphatic, and superficial growing metastasis type was proposed in 2012. Surgeons should perform peritonectomy according to the type of PM. Since 1980, Japanese surgical oncologists have been spearheading the use of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for PM from gastric cancer. Two RCTs were conducted to verify the effect of HIPEC for the prophylaxis of peritoneal recurrence after curative resection of advanced gastric cancer. These two studies indicated that HIPEC is effective in preventing peritoneal recurrence of gastric cancer with serosal invasion. In 2002, intraperitoneal chemotherapy using taxans was developed for the treatment of PM from gastric cancer and led to the development of neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), which was reported in 2006. In 2009, extensive intra-operative peritoneal lavage (EIPL) was developed, and contributed to the remarkable improvement in survival of patients with positive lavage cytology as demonstrated by prospective randomized clinical trials. In 2017, the Peritoneal Surface Oncology Group International proposed the value of complete cytoreduction and peritoneal cancer index cut-off as independent prognostic factors after CRS for gastric cancer with PM. Founded in 2016, the Japanese/Asian School of Peritoneal Surface Oncology (JASPSO) trains beginners to perform CRS and HIPEC safely. Sixteen students have already graduated from JASPSO and started to perform the treatment in their home countries.

Treatment of Peritoneal Surface Malignancies with Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (HIPEC): Experience in Israel.

The treatment of peritoneal surface malignancies, either primary or secondary (peritoneal metastasis), has evolved over the past two decades. A nihilistic approach of incurable "carcinomatosis" is changing into treatment of peritoneal metastasis with curative intent. The aim of the present study is to review the current practice, past history, and future of peritoneal surface oncology in Israel. A systematic review of all patients treated in institutions performing cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies. Each center provided the following data: start year, number of total cases, number of cases performed in 2017, and the method used (open vs. closed technique). Between 1990 and 2018, there were 1462 patients treated by CRS/HIPEC in Israel by eight different surgical groups in six medical centers. Currently, there are seven surgical groups in six medical centers routinely performing CRS/HIPEC. The annual rate of CRS/HIPEC was 171 cases in 2017 with a range of (4-69 cases/center). This is the first step of establishing an Israeli Peritoneal Surface Oncology Group that will have joined database and perform clinical trials in this challenging field of surgical oncology.

Evaluation of the Biological Behavior of a Gold Nanocore-Encapsulated Human Serum Albumin Nanoparticle (Au@HSANP) in a CT-26 Tumor/Ascites Mouse Model after Intravenous/Intraperitoneal Administration.

Colorectal cancer is one of the major causes of cancer-related death in Taiwan and worldwide. Patients with peritoneal metastasis from colorectal cancer have reduced overall survival and poor prognosis. Hybrid protein-inorganic nanoparticle systems have displayed multifunctional applications in solid cancer theranostics. In this study, a gold nanocore-encapsulated human serum albumin nanoparticle (Au@HSANP), which is a hybrid protein-inorganic nanoparticle, and its radioactive surrogate 111In-labeled Au@HSANP (111In-Au@HSANP), were developed and their biological behaviors were investigated in a tumor/ascites mouse model. 111In-Au@HSANP was injected either intravenously (iv) or intraperitoneally (ip) in CT-26 tumor/ascites-bearing mice. After ip injection, a remarkable and sustained radioactivity retention in the abdomen was noticed, based on microSPECT images. After iv injection, however, most of the radioactivity was accumulated in the mononuclear phagocyte system. The results of biodistribution indicated that ip administration was significantly more effective in increasing intraperitoneal concentration and tumor accumulation than iv administration. The ratios of area under the curve (AUC) of the ascites and tumors in the ip-injected group to those in the iv-injected group was 93 and 20, respectively. This study demonstrated that the ip injection route would be a better approach than iv injections for applying gold-albumin nanoparticle in peritoneal metastasis treatment.