Peritoneal Carcinomatosis Of Gastric Origin Research Articles

Imaging of Gastric Carcinomatosis.

Diagnosing the absence or presence of peritoneal carcinomatosis in patients with gastric cancer, including its extent and distribution, is an essential step in patients’ therapeutic management. Such diagnosis still remains a radiological challenge. In this article, we review the strengths and weaknesses of the different imaging techniques for the diagnosis of peritoneal carcinomatosis of gastric origin as well as the techniques’ imaging features. We also discuss the assessment of response to treatment and present recommendations for the follow-up of patients with complete surgical resection according to the presence of risk factors of recurrence, as well as discussing future directions for imaging improvement.

Cytoreductive Surgery for Peritoneal Carcinomatosis from Gastric Cancer: Technical Details.

Due to limited systemic treatment options, peritoneal carcinomatosis of gastric origin is still associated with a dismal outcome and is claimed a terminal disease. In the past, surgery had not been considered as a potential treatment option. However, there is emerging evidence that in selected patients, locoregional treatment modalities including cytoreductive surgery of peritoneal carcinomatosis can improve survival in patients with gastric cancer. These operative procedures are complex and challenging, and a high surgical expertise of the treating physician is necessary to prevent major postoperative morbidity and mortality with a delay of further systemic therapy. This review summarizes our current knowledge and personal experience regarding the techniques of cytoreductive surgery for peritoneal metastasis of gastric origin.

The Role of CAR-T Cells in Peritoneal Carcinomatosis from Gastric Cancer: Rationale, Experimental Work, and Clinical Applications.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown poor effectiveness in treating peritoneal carcinomatosis (PC) of gastric origin with a high tumor burden (high peritoneal cancer index), though there are scarce therapy alternatives that are able to improve survival. In experimental studies, chimeric antigen receptor-T (CAR-T) cell therapy has shown encouraging results in gastric cancer and is currently being evaluated in several clinical trials. Regarding PC, CAR-T cell therapy has also proven useful in experimental studies, especially when administered intraperitoneally, as this route improves cell distribution and lifespan. Although these results need to be supported by ongoing clinical trials, CAR-T cells are a promising new therapeutic approach to peritoneal metastases from gastric cancer. In this review, we summarize the current evidence of the use of CAR-T cells in gastric cancer and PC of gastric origin.

Effect of Pressurized Intraperitoneal Aerosol Chemotherapy on the Survival Rate of Patients with Peritoneal Carcinomatosis of Gastric Origin.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new surgical technique for the treatment of initially unresectable peritoneal carcinomatosis (PC). Our objective was to compare the results of PIPAC associated with systemic chemotherapy (PIPAC_CHEM) with those of systemic chemotherapy alone (ONLY_CHEM) in patients with gastric PC without metastasis other than peritoneal, and the WHO performance status < 3. This was a retrospective, single center, comparative non-randomized study. Seventeen PIPAC_CHEM patients were compared to 29 ONLY_CHEM patients. The primary endpoint was overall survival at 6months from diagnosis of PC. Ninety-eight patients were screened and 46 were included (PIPAC_CHEM, n = 17; ONLY_CHEM, n = 29). The PIPAC_ CHEM population was significantly younger (median 64years [56; 68] vs 74years [61; 79]; p = 0.0054). Median PIPAC session per patient is 2 [1-3]. Six-month survival was significantly higher in the PIPAC_CHEM group than in the ONLY_CHEM group 16/17 (94.1% [65-99.2]) vs 19/29 (65.5% [45.4-79.7]), respectively; p = 0.029. Over the entire follow-up, median survival [95% CI] was 12.8months [7.2-34.3] with PIPAC vs 9.1months [5.4-11.5] without, p = 0.056. At 6months, median length of additional hospitalization was significantly less for PIPAC_CHEM (median 2days [2-7]) than without PIPAC (median 11days [3-21]) (p = 0.045). The overall survival at 6months after the diagnosis of carcinomatosis was significantly better for PIPAC_CHEM patients. This difference appears to continue until at least 18months. At 6months, days of additional hospitalization was significantly less in the PIPAC_CHEM group. Clinicaltrials.gov Identifier: NCT 04,879,953.

A narrative review of intraperitoneal chemotherapy and cytoreductive surgery (CRS) for peritoneal metastases in gastric cancer.

Peritoneal carcinomatosis of gastric origin is an aggressive tumor entity. Historically it has been considered a terminal disease with no long-term survival, due to limited therapeutic options. However, as a better understanding of tumor biology has evolved in recent years, novel multimodal treatment strategies incorporating intraperitoneal (IP) chemotherapy-hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)-and cytoreductive surgery (CRS) have demonstrated promising oncologic outcomes and even long-term survival in selected patients. Most of the studies published to date are retrospective in nature. These studies involve heterogenous patient populations, a wide variety of chemotherapeutic drugs, and show wide variation in outcomes between institutions. Thus, it is difficult to evaluate the results. This review summarizes our current knowledge regarding IP chemotherapy and CRS for peritoneal metastases (PM) in gastric cancer (GC). We describe our institutional treatment regimens. We also provide a brief overview of new, targeted therapies that may show promise in the future.

Peritoneal Carcinomatosis of Gastric Origin - Treatment Possibilities.

Peritoneal carcinomatosis of gastric origin is challenging to diagnose and treat. This disease is often misdiagnosed in the early stages using a non-invasive technique. Conventional surgery is unsuitable for treatment of patients with peritoneal seeding and positive peritoneal cytology. Peritoneal recurrence is the most frequent cause of therapeutic failure. The effectiveness of chemotherapy is low due to the plasma-peritoneal barrier. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard treatment for pseudomyxoma peritonei and mesothelioma and improves overall survival and disease-free survival. This approach is also widely used to prevent and treat peritoneal carcinomatosis of gastric origin. This article aims to provide a short summary of the contemporary role of cytoreductive surgery and HIPEC for treatment of gastric cancer patients. Theoretically, there are four possible applications and indications. First, palliative application to improve quality of life without prolongation of overall survival. This application mainly affects malignant ascites. Second, therapeutic application using a combination of gastrectomy/cytoreductive surgery and HIPEC to treat advanced disease including peritoneal metastases. Localized peritoneal seeding is the only indication for this application (maximum peritoneal cancer index of 10-12 or Cy+). Third, adjuvant/prophylactic application in patients at high risk of peritoneal recurrence, typically those with T3, T4, N+ disease (without peritoneal seeding). Fourth, neoadjuvant application using a combination of repeated HIPEC and chemotherapy with the aim of decreasing peritoneal seeding and enabling radical surgery. In this indication, HIPEC is often replaced by pressurized intraperitoneal aerosol chemotherapy.

Role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer.

Patients with peritoneal carcinomatosis (PC) of gastric origin have a poor prognosis of life with an average survival of 1-3 months. Systemic chemotherapy has improved the survival of those patients with gastric metastatic cancer at 7-10 months. However, this benefit could not be reproduced in those patients with PC. The current literature for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) for gastric PC has significant variation related to patient selection, treatment intent (palliative vs. attempt at curative treatment), surgical technique, intraperitoneal chemotherapy agent utilized, and systemic chemotherapy administered adjuvantly. From the perspective of patient selection for cytoreduction and HIPEC, patients with extensive PC are not candidates. In addition, unresectable location would make a patient a poor candidate for cytoreduction and HIPEC. Optimally, those with positive peritoneal cytology alone could benefit most. However, the role of cytoreductive surgery and HIPEC in patients with PC of gastric origin has not yet been clarified.

Hyaluronan-binding peptide for targeting peritoneal carcinomatosis.

Peritoneal carcinomatosis results from dissemination of solid tumors in the peritoneal cavity, and is a common site of metastasis in patients with carcinomas of gastrointestinal or gynecological origin. Peritoneal carcinomatosis treatment is challenging as poorly vascularized, disseminated peritoneal micro-tumors are shielded from systemic anticancer drugs and drive tumor regrowth. Here, we describe the identification and validation of a tumor homing peptide CKRDLSRRC (IP3), which upon intraperitoneal administration delivers payloads to peritoneal metastases. IP3 peptide was identified by in vivo phage display on a mouse model of peritoneal carcinomatosis of gastric origin (MKN-45P), using high-throughput sequencing of the peptide-encoding region of phage genome as a readout. The IP3 peptide contains a hyaluronan-binding motif, and fluorescein-labeled IP3 peptide bound to immobilized hyaluronan in vitro. After intraperitoneal administration in mice bearing peritoneal metastases of gastric and colon origin, IP3 peptide homed robustly to macrophage-rich regions in peritoneal tumors, including poorly vascularized micro-tumors. Finally, we show that IP3 functionalization conferred silver nanoparticles the ability to home to peritoneal tumors of gastric and colonic origin, suggesting that it could facilitate targeted delivery of nanoscale payloads to peritoneal tumors. Collectively, our study suggests that the IP3 peptide has potential applications for targeting drugs, nanoparticles, and imaging agents to peritoneal tumors.

Prognostic factors of intraperitoneal chemotherapy for peritoneal carcinomatosis of gastric cancer: A retrospective study from a single center

Peritoneal carcinomatosis (PC) of gastric origin is currently recognized as a terminal disease with a poor prognosis. Advancements in novel therapeutic approaches, including intraperitoneal chemotherapy (IPC), have recently been made and it is believed that this may have contributed to the improved survival observed in patients with PC. The present study aimed to investigate overall survival (OS) and the associated prognostic factors in patients with PC of gastric origin who underwent IPC. A total of 57 patients were studied, with a median age of 51 years. The median follow-up time was 12.4 months. PC was diagnosed in all patients with gastric cancer. The median survival time of all patients was 10.1 months, whilst the OS rate at 1, 2 and 3 years was observed to be 46, 19 and 12%, respectively. Symptomatic ascites and a signet ring cell (SRC) histopathological type were demonstrated to signify a poor prognosis. Complete resection of all gross disease (CCR-0) and an increased number of cycles of systemic chemotherapy were independent factors that were observed to correlate with increased OS. The most common morbidities of grade 3/4 adverse effects were bone marrow suppression, nausea or vomiting, and diarrhea. In conclusion, IPC is an important treatment option for patients with PC that has originated from gastric cancer. Symptomatic ascites and SRC adenocarcinoma serve as negative clinicopathological prognostic factors, whilst CCR-0 and increased systemic chemotherapy cycles (≥4 cycles) may prove to be an important therapeutic option for PC patients.

Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin--a longitudinal experience from a prospectively collected database of 1108 patients.

BackgroundComprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking.MethodsData from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively.ResultsDespite R0 D2 gastrectomy (n = 560), 49.6% (±5.4%) of the patients were diagnosed with tumour recurrence and 15.5% (±1.8%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100% with a median survival of 3.0 months (2.1 – 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54).ConclusionsDespite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition.

Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial.

A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis. Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum, and resectable to "no evidence of disease" were randomized to gastrectomy, metastasectomy, HIPEC, and systemic FOLFOXIRI (GYMS arm) or FOLFOXIRI alone (SA arm). Seventeen patients were enrolled (16 evaluable); 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction (CCR0). Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm. Four patients in the GYMS arm survived >12 months, 2 patients close to 2 years at last follow-up, and 1 patient more than 4 years, with 2 of these patients still alive. No patient in the SA arm lived beyond 11 months. All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index (PCI) of ≤ 15. Maximal cytoreductive surgery combined with regional (HIPEC) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival.

Hyperthermic intraperitoneal chemoperfusion in combined treatment of locally advanced and disseminated gastric cancer: Results of a single-centre retrospective study

Background: Patients with locally advanced gastric cancer (GC) and/or peritoneal metastases have a poor prognosis despite systemic chemotherapy or palliative surgery. The aim of this retrospective comparative non-randomised study was to evaluate aggressive cytoreduction in combination with hyperthermic intraperitoneal chemoperfusion (HIPEC) as a novel treatment strategy for patients with intraperitoneal disseminated and locally advanced GC.Patients and methods: Forty-nine GC patients with serosal invasion (n = 19), limited peritoneal metastases (n = 20), or disseminated peritoneal metastases and tense ascites (n = 10) underwent combination therapy with HIPEC. Three matched control groups undergoing standard therapies were retrospectively identified.Results: Combination therapy for serosa-invasive GC reduced the level of metachronous peritoneal carcinomatosis and increased median survival from 12 months to 22.5 months (p = 0.001). The median and 1-year survival rates for intraperitoneal disseminated GC patients undergoing therapy with the use of HIPEC were 12 months and 68.8% compared with 8 months and 25%, respectively (p = 0.004) for control subgroup patients (palliative chemotherapy). The symptomatic use of HIPEC allows effective elimination of recurrent ascites in GC patients.Conclusion: HIPEC is a well-tolerated and effective method of adjuvant therapy for gastric cancer with high risk of intraperitoneal progression. Cytoreduction followed by HIPEC improves survival in patients with limited peritoneal carcinomatosis of gastric origin.

The Treatment of Peritoneal Carcinomatosis in Advanced Gastric Cancer: State of the Art

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death in the world; 53–60% of patients show disease progression and die of peritoneal carcinomatosis (PC). PC of gastric origin has an extremely inauspicious prognosis with a median survival estimate at 1–3 months. Different studies presented contrasting data about survival rates; however, all agreed with the necessity of a complete cytoreduction to improve survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) has an adjuvant role in preventing peritoneal recurrences. A multidisciplinary approach should be empowered: the association of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), cytoreductive surgery (CRS), HIPEC, and early postoperative intraperitoneal chemotherapy (EPIC) could increase the rate of completeness of cytoreduction (CC) and consequently survival rates, especially in patients with Peritoneal Cancer Index (PCI) ≤6. Neoadjuvant chemotherapy may improve survival also in PC from GC and adjuvant chemotherapy could prevent recurrence. In the last decade an interesting new drug, called Catumaxomab, has been developed in Germany. Two studies showed that this drug seems to improve progression-free survival in patients with GC; however, final results for both studies have still to be published.

Peritoneal carcinomatosis of gastric origin: A population‐based study on incidence, survival and risk factors

Peritoneal carcinomatosis (PC) is an important cause of morbidity and mortality among patients with gastric cancer. The aim of the current study was to provide reliable population-based data on the incidence, risk factors and prognosis of PC of gastric origin. All patients diagnosed with gastric cancer in the area of the Eindhoven Cancer Registry between 1995 and 2011 were included. Incidence and survival were computed and risk factors for peritoneal carcinomatosis were determined using multivariate logistic regression analysis. In total, 5,220 patients were diagnosed with gastric cancer, of whom 2,029 (39%) presented with metastatic disease. PC was present in 706 patients (14%) of whom 491 patients (9%) had PC as the only metastatic site. Younger age (<60 years), female gender, advanced T- and N-stage, primary tumor of signet ring cells or linitis plastica and primary tumors covering multiple anatomical locations of the stomach were all associated with a higher odds ratios of developing PC. Median survival of patients without metastases was 14 months, but only 4 months for patients with PC. PC is a frequent condition in patients presenting with gastric cancer, especially in younger patients with advanced tumor stages. Given the detrimental influence of PC on survival, efforts should be undertaken to further explore the promising results that were obtained in preventing or treating this condition with multimodality strategies.

Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of malignant ascites secondary to unresectable peritoneal carcinomatosis from advanced gastric cancer

Aims To review our experience of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of malignant ascites from advanced gastric cancer in order to discuss benefits, problems and possible indications. Methods From June 2000 to May 2003 laparoscopic approach was used to perform HIPEC on five patients affected by malignant ascites secondary to unresectable peritoneal carcinomatosis of gastric origin, in order to associate the benefits of a definitive palliation of ascites with a minimal invasiveness. All patients had ascites related symptoms requiring iterative paracenteses. Intraperitoneal perfusion of mitomycin-C and cisplatin was delivered for 60–90 min with an inflow temperature of 45 °C. Results Complete clinical regression of ascites and related symptoms was achieved in all the five patients treated. Intraoperative course was uneventful in all cases. Mean operative time was 181 min. No postoperative deaths, related to the procedure, occurred. Only a case of delayed gastric empting was recorded as a minor postoperative complication. Conclusions Laparoscopic HIPEC appears to be a safe and effective procedure to treat debilitating malignant ascites from unresectable peritoneal carcinomatosis.