Important Predictive Factors for the Prognosis of Patients With Peritoneal Metastasis of Gastric Cancer.

BACKGROUND: This study investigated predictive factors for patients with peritoneal metastases of gastric cancer (PMGC) who underwent conversion cytoreductive surgery (C-CRS) and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC) after responding to induction chemotherapy (laparoscopic HIPEC [LHIPEC]) followed by concomitant systemic and intraperitoneal chemotherapy (bidirectional intraperitoneal and systemic chemotherapy [BIC]). METHODS: Diagnostic laparoscopy was performed for 62 patients with PMGC between January 2017 and December 2022. The patients underwent LHIPEC and BIC induction chemotherapy using intraperitoneal docetaxel (30 mg/m2) and cisplatin (30 mg/m2), and intravenous chemotherapy for three cycles. The predictive parameters for progression-free and overall survival were analyzed using Kaplan-Meier and Cox regression analyses. The optimal cutoff values for Ki-67 parameters were assessed using receiver operating characteristic curve analysis. RESULTS: The study retrospectively examined 36 (58 %) of 62 patients who responded to induction therapy and underwent C-CRS or HIPEC. A Ki-67 index lower than 10 (p = 0.000), lymph node involvement (LNI) less than 2 (p = 0.039), and an omental lesion size score lower than 0.5 cm (p = 0.002) were predictive of recurrence-free and overall survival in addition to completeness of cytoreduction and the peritoneal cancer index. Cox regression analysis showed that the independent factors associated with recurrence-free survival were decreased Ki-67 expression (≥10 % vs <10 %) (hazard ratio [HR] 4.7; 95 % confidence interval [CI] 1.6-5.210; p = 0.020) and LNI higher than 2 (HR 1.92; 95% CIS 0.923-4.0; p = 0.023). CONCLUSIONS: Lymph node involvement and decreased Ki-67 expression are independent predictive factors of recurrence-free survival for patients with PMGC after induction chemotherapy.

Feasibility of Robot-Assisted Cytoreductive Surgery With Upper-Abdominal Peritonectomy for Pseudomyxoma Peritonei With Low Peritoneal Carcinomatosis Index: A Pilot Study.

INTRODUCTION: Our study's objective was to provide the method for, and preliminary findings from, robot-assisted cytoreductive surgery (r-CRS) combined with upper-abdominal peritonectomy in pseudomyxoma peritonei (PMP) with limited peritoneal surface malignancy (PSM). MATERIALS AND METHODS: We conducted a retrospective pilot study on consecutive patients with PSM secondary to pseudomyxoma peritonei with a peritoneal cancer index (PCI) of under 10 who were indicated for r-CRS combined with upper-abdominal peritectomy. Perioperative and 30-day major morbidity and mortality characteristics were analyzed and compared with cases in which laparoscopic CRS (l-CRS) was performed under the same conditions. RESULTS: Six patients underwent r-CRS combined with an upper-abdominal partial peritonectomy. Their mean PCI was 4.83. Complete cytoreduction was achieved in all patients. The mean duration of the operation was 156.8 minutes. There was no major complication and no mortality. The mean length of hospital stay after surgery was 6.33 days. r-CRS resulted in less blood loss, a lower C-reactive protein level, and a shorter length of hospital stay that were significantly different compared with those of l-CRS. CONCLUSIONS: This is the initial technical report of a robotic approach for CRS combined with upper-abdominal peritonectomy. r-CRS with a combined upper-abdominal peritonectomy was shown to be safe and feasible for PMP with limited PSM.

Cytoreductive surgery for synchronous and metachronous colorectal peritoneal dissemination: Japanese P classification and peritoneal cancer index.

Aim: The outcomes of cytoreductive surgery (CRS) for synchronous and metachronous colorectal peritoneal dissemination were investigated using the Japanese P classification and peritoneal cancer index (PCI). Methods: CRS was performed in 111 cases of synchronous peritoneal dissemination and 115 cases of metachronous peritoneal dissemination. The P classification and PCI were determined at the time of laparotomy. Results: In the synchronous dissemination group, the 5-year overall survival rates after CRS in P1/P2 and P3 cases were 51% and 13%, respectively. Even for P3, 51% of the patients achieved macroscopic cytoreductive complete resection (CC-0), with a 5-year survival rate of 40%. When P3 cases were classified into PCI 0-9, 10-19, 20-29, and 30-39, CC-0 was achieved in 93%, 70%, 6%, and 0% of the cases, respectively, and the 5-year survival rate of PCI 0-9 was 41%. In the metachronous dissemination group, the 5-year survival rates were 62% for PCI 0-9 and 22% for PCI 10-19; 5-year survival was not observed in patients with a PCI ≥ 20. CC-0 was significantly associated with the postoperative prognosis in both synchronous and metachronous peritoneal dissemination. Conclusion: In cases of synchronous dissemination, CRS must be performed for P1 and P2 cases or those with a PCI < 10, while detailed examination using PCI is required for P3 cases. In cases of metachronous dissemination, CRS should be considered when the PCI score is <20.

Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells.

Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.

Analysis of the characteristics and outcomes of patients with pseudomyxoma peritonei of appendiceal origin treated with curative-intent surgery.

BACKGROUND: There are no previous studies on pseudomyxoma peritonei regarding the details of surgical procedures included in cytoreductive surgery and quantitative evaluation for peritoneal metastases by region in the abdominal cavity. This study aimed to describe the characteristics and procedural details involved in cytoreductive surgery, and survival outcomes of patients with pseudomyxoma peritonei originating from appendiceal mucinous neoplasm, and identify differences in the difficulty of cytoreductive surgery based on tumor location. METHODS: Patient characteristics and survival outcomes were studied through a retrospective review. The complete cytoreduction rate (i), the 5-year survival rate for patients with complete cytoreduction (ii), and an index as a complement (i × ii × 100) were described for patients who had tumors larger than 50 mm in one of the 13 regions of the abdominal cavity. RESULTS: A total of 989 patients were treated with curative-intent cytoreductive surgery. The median peritoneal cancer index was 18 (interquartile range, 6-29), with complete cytoreduction achieved in 702 patients (71%); the major complication rate was 17%. The median overall survival was 92.9 months, compared to 53.8 months for patients who underwent total gastrectomy and 30.4 months for those who underwent total colectomy. In the 13 abdominal regions, the index scores indicating cytoreduction difficulty were categorized into three risk groups: upper and mid-abdominal (>20), lateral abdominal (10-20), and small bowel (<10). CONCLUSIONS: Cytoreductive surgery offered favorable survival outcomes, even in cases involving total gastrectomy. The difficulty of achieving complete cytoreduction varied across abdominal regions and was classified into three levels.

Correction: Noguchi et al. Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei. J. Pers. Med. 2022, 12, 258.

There was an error in the original publication [...].

Benefit of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy and Bidirectional Chemotherapy for Patients with Gastric Cancer with Peritoneal Carcinomatosis Considering Cytoreductive Surgery.

Comprehensive treatment comprising neoadjuvant laparoscopic HIPEC (L-HIPEC) and bidirectional intraperitoneal and systemic induction chemotherapy (BISIC) followed by cytoreductive surgery (CRS) for gastric cancer with peritoneal carcinomatosis (PC) has been developed. However, its benefits and patient selection criteria have not been thoroughly investigated. We retrospectively reviewed 113 patients, with 25 having received comprehensive treatment (L-HIPEC, BISIC, and then CRS-HIPEC; the BISIC group) and 88 having received direct CRS-HIPEC (the CRS group). The BISIC group showed greater tumor clearance in terms of post-CRS peritoneal cancer index ((PCI) 6 vs. 14, p = 0.002) compared to CRS group. The median survival was 20.0 months in the BISIC group and 8.6 months in the CRS group (p = 0.031). Multivariable analysis revealed that the factors associated with increased survival were the BISIC protocol, age, and post-CRS tumor clearance. BISIC significantly improved survival in cases of moderate severity (PCI 11-20) and severe cases (PCI 21-39) without increasing the morbidity rate. We recommend the use of this neoadjuvant strategy for patients with gastric cancer-associated PC and an initial PCI of >10 to provide superior survival outcomes.

Meckel's Diverticulum Carcinoma Is Arrested by Oxaliplatinum and Eradicated by 5-Fluorouracil in a PDX Mouse Model Indicating Candidate First-line Treatment for a Rare Cancer.

BACKGROUND/AIM: Meckel's diverticulum carcinoma (MDCa) is extremely rare. It is often advanced when found, and the prognosis is poor. Effective treatment for this cancer has not yet been developed. We previously established a patient-derived xenograft (PDX) nude-mouse model of MDCa. In the present study, we investigated the efficacy of oxaliplatinum (L-OHP) and 5-fluorouracil (5-FU) on an MDCa PDX nude-mouse model. MATERIALS AND METHODS: PDX mouse models of MDCa were divided into three groups (five mice per group): untreated control; L-OHP-treated; and 5-FU-treated. Tumor volumes of the three groups were compared after 2 weeks. RESULTS: L-OHP arrested tumor growth (p=0.038) and 5-FU apparently eradicated the tumor (p=0.007). CONCLUSION: L-OHP and 5-FU are candidates for clinical first-line therapy of MDCa.

Comparison of Cytoreductive Surgery and Resection of Isolated Peritoneal Metastases in Patients with Peritoneal Metastases from Colorectal Cancer: A Retrospective Study.

Objectives: This study aimed to compare the short and long-term outcomes of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy and resection of isolated peritoneal metastases in patients with peritoneal metastases from colorectal cancer in Japan. Methods: We included patients who had undergone surgery for peritoneal metastases from colorectal cancer between 2013 and 2019. Data were retrieved from a prospectively maintained multi-institutional database and retrospective chart review. Patients were classified into cytoreductive surgery and resection of isolated peritoneal metastases groups based on the surgery they had undergone. Results: A total of 413 patients were eligible for analysis (257 and 156 patients in the cytoreductive surgery and resection of isolated peritoneal metastases groups, respectively). There was no significant difference in overall survival (hazard ratio and 95% confidence intervals, 1.27 [0.81, 2.00]). Six cases (2.3%) of postoperative mortality were observed in the cytoreductive surgery group, whereas none were observed in the resection of the isolated peritoneal metastases group. Cases of postoperative complications were significantly higher in the cytoreductive surgery group (risk ratio 2.02 [1.18, 2.48]) than those in the resection of isolated peritoneal metastases group. Among patients with a high peritoneal cancer index (6 points or higher), the complete resection rate was 115/157 (73%) and 15/44 (34%) in the cytoreductive surgery and the resection of isolated peritoneal metastases groups, respectively. Conclusions: Cytoreductive surgery was not superior in providing long-term survival benefits for colorectal cancer peritoneal metastases; however, cytoreductive surgery provided a higher complete resection rate even in patients with a high peritoneal cancer index (6 points or higher).

Peritoneal metastasis of advanced epithelial ovarian carcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A retrospective international multicentric data analysis.

INTRODUCTION: The purpose of our study was to evaluate outcome data after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis originating from advanced epithelial ovarian carcinoma (PMOC). PATIENTS AND METHODS: A retrospective international multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group. RESULTS: One thousand four hundred and ninety-one patients from 11 specialized units underwent CRS and HIPEC that of those 326 (21.9%) upfront surgeries, 504 (33.8%) interval surgery, and 661(44.3%) recurrent cases. Complete Cytoreduction(CC0/1) was achieved in 1213 patients (81.3%). Treatment -related mortality was 0.8%, major operative complications (Grades 3-5) was 25.1%. Factors associated with major operative complications include prior surgical score (PSS for recurrent cases; RC) PSS>2,p = 0.000), PCI(≤15, >15 cut-off level; p ≤ 0.000), completeness of cytoreduction (CC, p=0.000), high CA125 levels (>25 mg/dl), presence of ascites, high CRP (>5 mg/dl) levels and low albumin levels (below to 2.5 mg/dl) (p ≤ 0.05). The median survival was 58 months in upfront surgery(UFS), 60 months in interval surgery(IS), and 42 months in RC. The overall survival for five years was 45% for UFS, 37% for IS, 28% for RC cases. CCscore (p = 0.000), CA125, CRP and albumin levels (p ≤ 0.05) were predictors for progression free survival. PCI(p ≤ 0.000), major postoperative complications (p = 0.004), incomplete CRS(CC2/3)(p < 0.001), prior chemotherapy (hazard ratio [HR], 3-8; p < 0.001) and PSS>2 for RC were independent predictors of poor overall survival. CONCLUSION: The combined treatment strategy for PMOC may be performed safely with acceptable morbidity and mortality in the specialized units.

[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

[Pseudomyxoma Peritonei Caused by Intraductal Papillary Mucinous Neoplasm-A Three Case Series].

Pseudomyxoma peritonei(PMP)is a rare condition caused by intraductal papillary mucinous neoplasm(IPMN). At our institution, 3 cases, along with literature review, of PMP caused by IPMN were treated with cytoreductive surgery. In case 1, a 70-year-old man was pathologically diagnosed with low-grade PMP with intraductal papillary mucinous carcinoma. Recurrence was discovered 68 months after surgery, and the patient died after 78 months. In case 2, a 69-year-old man was pathologically diagnosed with high-grade PMP with signet-ring cell carcinoma caused by intraductal papillary mucinous carcinoma. The patient died 8 months post-surgery. In case 3, a 77-year-old woman was pathologically diagnosed with low- grade(partially high-grade)PMP with intraductal papillary mucinous adenoma. There was a recurrence 14 months post- surgery. The patient is still alive because of systemic chemotherapy 32 months after surgery.

Gastric Cancer With Peritoneal Metastasis-A Comprehensive Review of Current Intraperitoneal Treatment Modalities.

The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients' general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.

The First Mouse Model of Meckel's Diverticulum Carcinoma.

BACKGROUND: Cancer of the Meckel's diverticulum (MD) is extremely rare. It is often advanced at the time of operation and the prognosis is poor. An effective treatment for this cancer has not yet been developed and there is no MD-carcinoma mouse model. MATERIALS AND METHODS: MD carcinoma was established as a patient-derived xenograft (PDX) in 5-week-old male nude mice by subcutaneous transplantation of surgical specimens together with surrounding normal tissue. Hematoxylin and eosin (H&E) staining was performed on paraffin-embedded tissue sections of the original tumor resected from patients and transplanted tumors grown in nude mice. RESULTS: Three of five mice implanted with MD tumor fragments grew. MD-carcinoma histopathology, observed with H&E-stained tissue sections of the tumors grown in the mice and tumor from the original patient, was concordant. Both showed the luminal structures characteristic of MD carcinoma, and the lumens were filled with serous fluid. CONCLUSION: The first PDX mouse model of MD carcinoma has been established. The PDX model maintained MD-carcinoma histology of the tumor in the patient. The MD carcinoma mouse model will enable basic research on MD carcinoma, as well as the testing of novel therapeutic agents.

Mesentery solitary fibrous tumor with postoperative recurrence and sarcomatosis: A case report and review of literature.

BACKGROUND: Solitary fibrous tumors are rare neoplasms of mesenchymal origin. They are often of low malignant potential and rarely metastasize. They frequently arise from the pleura and can occur at any soft tissue site in the body. However, these tumors rarely develop in the mesentery, peritoneal cavity or peritoneum. CASE SUMMARY: We report on a scarce case of solitary fibrous tumor of the rectal mesentery showing sarcomatosis about 4 years after previous tumor resection. This 69-year-old male had no clinical symptoms but was transferred to our hospital because of a suspected tumor recurrence from follow-up abdominal computed tomography. Tumor markers (CEA, CA 19-9 and CA 125) were within the normal range. Open laparotomy showed sarcomatosis, and pathology confirmed its mesenchymal origin and diagnosis as the solitary fibrous tumor. Our case may be the second recurrent mesentery solitary fibrous tumor reported to date, and the only one with progression to sarcomatosis. There has been no evidence of recurrence in follow-up at the 28th mo after extensive intra-operative peritoneal lavage and cytoreductive surgery. CONCLUSION: Although there are few risk factors of cancer recurrence in this patient, careful long-term follow-up after cytoreductive surgery is necessary.

Recurrence of initially localized appendiceal mucinous neoplasms after radical resection: survey analysis and literature review.

BACKGROUND: Appendiceal mucinous neoplasm (AMN) is a rare tumor that may be successfully treated by appendectomy. However, some patients develop recurrence as pseudomyxoma peritonei. The present study investigated the recurrence rate after radial resection for AMN. METHODS: A survey on AMN was sent to 171 institutions, and 286 cases were analyzed. The risk of recurrence was assessed according to clinical parameters. Recurrence rates were compared with data from the literature. RESULTS: There were 250 cases in the low-grade group and 36 in the high-grade group, with perforation being detected in 50 cases. After a median follow-up period of 30 months, recurrence was detected in 17 cases, including 12 with high-grade histology and 10 with perforation. Two patients with low-grade histology and no perforation developed recurrence. Independent prognostic factors for recurrence were high-grade histology (p = 0.0001, RR = 8.56) and perforation (p = 0.0168, RR = 3.45). Four groups were classified by histology and perforation: group A: high-grade, perforation ( +), group B: high-grade, perforation (-), group C: low-grade, perforation ( +), group D: low-grade, perforation (-). Five-year recurrence rates in groups A, B, C, and D were 46.7, 25.9, 13.3, and 1.5%, respectively. All cases of recurrence were detected within 3 years, except for two in group B. CONCLUSIONS: Recurrence in cases with low-grade histology and no perforation was rare; however, a postoperative survey for at least 3 years is required. In contrast, cases with high-grade histology or perforation need to be monitored using a similar approach to colon cancer. Prophylactic CRS + HIPEC may be considered.

Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei.

Pseudomyxoma peritonei (PMP) is the intraperitoneal accumulation of mucus due to a mucinous tumor. PMP predominantly occurs in low-grade carcinomas. The incidence rate of PMP is one to two cases per million people per year. The standard therapy of PMP comprises complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PMP recurs in about 50% of patients, and 30-40% are unable to receive the standard treatment because of its invasiveness. Therefore, novel therapies are of the utmost necessity. For basic and pre-clinical research, patient-derived cell lines are essential resources. However, only two PMP cell lines have been reported. Thus, we established a novel PMP cell line from resected metastatic PMP tissue. The cell line, named NCC-PMP1-C1, was maintained for more than 5 months and was passaged 25 times. NCC-PMP1-C1 cells demonstrated multiple amplifications and deletions, slow growth, tumorigenic ability, and dissemination of tumor cells in nude mice. We also used NCC-PMP1-C1 cells to screen drugs, which demonstrated a significant response to daunorubicin HCl, homoharringtonine, mitomycin C, and ponatinib. The NCC-PMP1-C1 cell line is the first PMP cell line derived from metastasized tissue and will be a potential resource for basic and pre-clinical research of metastasized PMP.

The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5'-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

Rationale of Treatment for Peritoneal Metastasis.

In 1998, the Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment referred to as comprehensive treatment(COMPT). COMPT involves the complete removal of macroscopic tumors(cytoreductive surgery: CRS) and eradication of micrometastasis(MM)with neoadjuvant chemotherapy(NAC)plus intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC). This article provides a rationale for curative COMPT. Additionally, based on our experience, the selection criteria for treatment will be clarified. RATIONALE: The residual cancer cell burden is lowest immediately following CRS, and intraoperative HIPEC plays a crucial role in the treatment of patients with peritoneal surface malignancy (PSM). COMPT will fail if the number of the MM remaining after CRS exceeds the limit of complete eradication by intraoperative HIPEC(threshold). However, if the residual number of MM is less than the threshold, patients will respond positively to treatment. PATIENTS AND METHODS: To validate the direct effect of HIPEC, laparoscopic HIPEC(LHIPEC)was performed, and changes in the peritoneal cancer index(PCI)were then evaluated. Complete cytoreduction and HIPEC carried out based on the concept of COMPT was performed in 171 gastric cancer(GC)patients with PCI≤12, 183 colorectal cancer(CRC)with PCI≤21 and 460 pseudomyxoma peritonei(PMP)patients with PCI≤28. The postoperative survivals rates were then analyzed. RESULTS: After 1 cycle of LHIPEC, PCIs in GC and PMP were significantly reduced by 1.85 and 2.7 1 month after LHIPEC. However, PCI of CRC increased. Positive cytology at LHIPEC became negative in 57.6%, 42.9% and 60.9% of patients with GC, CRC and PMP, respectively. Median survival time(MST)for GC and CRC was 21.2 and 71.5 months, respectively MST of PMP was not reached. MST of PMP was not reached. Ten-year survival rates were 12.6%, 21.7% and 81.6%, respectively. Grade 5 complications for each disease were 0.8%, 1.0% and 1.1%, respectively. CONCLUSIONS: Complete cytoreductive surgery combined with intraoperative HIPEC may improve the long-term survival of patients with PSM who have PCIs less than the threshold levels, by keeping the mortality rates after CRS plus intraoperative HIPEC within acceptable levels.

The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI.

BACKGROUND: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). METHODS: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. RESULTS: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2-7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0-2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2-2.6) years. CONCLUSIONS: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.