Peritoneal Malignancies Research Articles

Anatomical Targeting of Anticancer Drugs to Solid Tumors Using Specific Administration Routes: Review.

Despite remarkable recent progress in developing anti-cancer agents, outcomes of patients with solid tumors remain unsatisfactory. In general, anti-cancer drugs are systemically administered through peripheral veins and delivered throughout the body. The major problem with systemic chemotherapy is insufficient uptake of intravenous (IV) drugs by targeted tumor tissue. Although dose escalation and treatment intensification have been attempted in order to increase regional concentrations of anti-tumor drugs, these approaches have produced only marginal benefits in terms of patient outcomes, while often damaging healthy organs. To overcome this problem, local administration of anti-cancer agents can yield markedly higher drug concentrations in tumor tissue with less systemic toxicity. This strategy is most commonly used for liver and brain tumors, as well as pleural or peritoneal malignancies. Although the concept is theoretically reasonable, survival benefits are still limited. This review summarizes clinical results and problems and discusses future directions of regional cancer therapy with local administration of chemotherapeutants.

A phase 1/2 open-label, multicenter, dose escalation and expansion study of AVB-001, an intraperitoneally administered, cell-generated, human IL-2 immunotherapy in patients with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube.

TPS5616 Background: The potential of cytokines as cancer therapeutics has been limited by short half-life and severe adverse effects associated with high systemic exposure when delivered intravenously. Many strategies are being explored to overcome these limitations. A locoregional delivery approach to achieve high sustained local concentrations in the tumor microenvironment with minimal systemic exposure could widen the therapeutic window. Early experience with free recombinant human IL2 (rhIL-2) given intraperitoneally (IP) showed meaningful clinical activity in relapsed ovarian cancer. Still, the cumbersome delivery procedure requiring indwelling catheters and need for high volume IP infusions leading to frequent complications and poor patient compliance limited the utility of this approach. To overcome these shortcomings, we developed a clinically translatable localized delivery LOCOcyte platform composed of polymer encapsulated allogeneic epithelial cells engineered to produce immune effector molecules for local delivery with temporal regulation. The first product, AVB-001, produces native hIL-2, for the treatment of ovarian cancer and other peritoneal malignancies. IP AVB-001 inhibited tumor growth and improved survival in an in vivo ID8 ovarian cancer murine model. Sustained IL-2 production with well tolerated high IP concentrations were achieved, with >100x differential concentration vs. systemic blood levels in both mice and non-human primates. Strong local and systemic immune activating effects, optimized T cell profile and immune memory were observed without concomitant increase of T regs. The first in human study of AVB-001 in patients with advanced ovarian cancer (NCT05538624) is described here. Methods: Part 1 dose escalation exploring 4 ascending dose levels (capsules target production of 0.6, 1.2, 2.4, and 3.6 ug hIL2/kg/d) with a Bayesian Optimal Interval 3+3 design, in patients with recurrent high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube. A minimum of 12 and up to 24 patients will be enrolled to receive one dose of AVB-001 administered IP. The primary objective is to evaluate safety (Incidence and severity of adverse events per NCI CTCAE v5.0), tolerability, and feasibility of delivering AVB-001 IP, and establish the RP2D. Secondary objectives include assessment of antitumor activity (RECIST v1.1, iRECIST), pharmacokinetics, and pharmacodynamic correlates of immune activation. Part 2 will enroll 20 patients at the RP2D with efficacy as the primary objective. This multicenter study will be conducted at 5 sites, currently two sites are open. The first patient was dosed in December 2022. Recruitment in dose level 1 cohort continues. Clinical trial information: NCT05538624 .

Pressurized intra-peritoneal aerosol as a delivery system for macrophage reprogramming cellular therapy in conjunction with chemotherapy for the treatment of advanced peritoneal malignancies.

e14537 Background: Novel intraperitoneal delivery systems like Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC) increase the therapeutic access with encouraging responses in patients with peritoneal carcinomatosis unresponsive to systemic therapy. However, survival rates remain at 11-16 months, and treatment options are limited, especially in patients with high tumor burden. Allocetra, an innovative immunomodulatory cellular therapy, has demonstrated antitumor activity in preclinical peritoneal tumor models, reprogramming macrophage function in the tumor microenvironment. The clinical study assesses the applicability and safety of Allocetra given by pressurized intra-peritoneal aerosol, in conjunction with PIPAC. Methods: Allocetra is manufactured from mononuclear cells collected from healthy non-matched donors, and induced to undergo early apoptosis. Safety of administration via pressurized aerosol was assessed by cell recovery and function. The clinical study is a dose-finding safety study with inter- and intra-patient dose escalation of Allocetra to determine safety of intraperitoneal Allocetra administration via pressurized aerosol system (Capnopen, Capnomed, Germany), with PIPAC. Patients have advanced peritoneal cancer, non-eligible for Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC). Two cohorts (n=3) are treated with escalating doses of Allocetra at 6-week intervals. Two subsequent cohorts (n=3) include patients treated at the maximal tolerated dose, to evaluate the sequencing of Allocetra and PIPAC. Results: Allocetra pressurized aerosol delivery demonstrated stable and acceptable cellular profiles, recovery and potency. In the first clinical cohort (n=3), patients received escalating doses of 1 x 109, 2.5 x 109 and 5 x 109 Allocetra cells, followed by PIPAC. Patients’ primary diseases were advanced colon and appendicular carcinomas with multiple prior treatment cycles (chemotherapy, biologics and immunotherapy). Patients were followed for a median 15 weeks (range 7-32) for adverse events. Adverse event profile following combined treatment with Allocetra included mostly mild common post surgical events: abdominal pain, pain around surgical wound, shoulder pain, abdominal wall hematoma, rash around surgical wound, urinary tract infection, inferior epigastric artery bleeding, and infected hematoma. None were considered related to Allocetra. All the patients are alive and continue to be followed. Conclusions: Initial results from the study indicate a favorable safety profile following pressurized intra-peritoneal aerosol administration of Allocetra cellular therapy. Additional patients will be treated with escalating doses of Allocetra to assess safety and initial response to treatment. Clinical trial information: NCT05431907 .

Safety and efficacy of PIPAC in patients with ovarian cancer with peritoneal metastases: A first-in-US phase I study.

5554 Background: Epithelial ovarian cancer (EOC) is characterized by chemoresistant recurrences primarily confined to the intraperitoneal cavity, frequently leading to malignant small bowel obstructions. Intraperitoneal (IP) chemotherapy has been incorporated in EOC, but only in the first-line setting. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a novel IP drug delivery method that optimizes tissue penetration depth and drug distribution, to treat recurrent peritoneal malignancies. Recent trials outside the U.S. demonstrated partial to stable response following PIPAC in recurrent EOC. To date, no clinical trials have been completed investigating the role of PIPAC in EOC in the United States. Methods: We performed a multicenter prospective phase I trial using IP cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 via PIPAC at 6-week intervals. Patients were eligible if they had recurrent disease with peritoneal metastasis; extraperitoneal metastasis was allowed. The primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included progression free survival, PCI scoring, RECIST measurements, and quality of life (QoL). The patients with gastric and uterine cancers’ toxicity data were used but given inherent prognostic differences the treatment efficacy for these patients were not used in this analysis. Adverse event (AE) monitoring was graded using CTCAE spanning 18 weeks. Following completion of treatment (³2 PIPACs) patients were followed up every 12 weeks. QoL was measured using patient-reported assessments at 0, 6, 12, and 18 weeks. Baseline demographics were summarized. Mean change in PCI was calculated between cycle (C) 1 and 2, and cycle 2 and 3. Toxicities attributed to the surgery or PIPAC were reported with highest grade for each patient. Results: Nine heavily pretreated, recurrent patients were enrolled in the trial: 7 with platinum-resistant recurrent EOC, 1 with uterine cancer, and 1 with gastric cancer. PIPAC completion rate was 71.4%. Median age of participants was 65 years. Median prior lines of chemotherapy were 4 (range 2 - 10). No surgical complications occurred in the cohort. Two patients came off study: one for G3 abdominal pain and the other for G3 anorexia. For the EOC cohort, the median PCI reduction was -1.4% (C1 to C2) and -2.8% (C1 to C3). One low-grade serous EOC patient demonstrated a partial response based on RECIST criteria and received 6 cycles. Two EOC patients showed an initial response based on PCI reduction, but progressed following Cycle 2. Overall, QoL was stable. Conclusions: PIPAC with cisplatin/doxorubicin in platinum-resistant ovarian cancer is well tolerated. Intraperitoneal responses were seen in a subset of low-grade serous ovarian cancer patients, which may warrant further study. Heavily pretreated, platinum-resistant high-grade EOC patients derived limited intraperitoneal control from PIPAC monotherapy. Clinical trial information: NCT04329494 .

Safety and feasibility of hyperthermic intraperitoneal chemotherapy during interval cytoreductive surgery in patients with advanced high‐grade serous ovarian, fallopian tube, peritoneal cancer in an Australian context

To assess the safety and feasibility of hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS) in advanced high-grade serous ovarian, fallopian tube and peritoneal cancer within an Australian context. Data were collected from 25 consecutive patients undergoing CRS and HIPEC from December 2018 to July 2022 at the Peritoneal Malignancy Service at the Mater Hospital Brisbane, Australia. Data collected included demographics, clinical variables, surgical procedures and complications and intra-operative and post-operative indexes of morbidity. Twenty-five women who underwent CRS and HIPEC from December 2018 to July 2022 were included in analysis. Findings indicate that CRS with HIPEC is associated with low morbidity. While judicious patient selection is imperative, HIPEC during CRS was well tolerated by all patients and morbidity was comparable to results from the previously reported OVHIPEC-1 trial. HIPEC appears to be a safe and feasible addition to CRS for the treatment of advanced ovarian cancer in Australian practice.

A Review of the Use of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy in Pediatric Patients.

Hyperthermic intraperitoneal chemotherapy (HIPEC) can directly target microscopic peritoneal disease, has achieved regular consideration in the treatment of several adult cancer types, and is more recently being studied in pediatrics. This review paper provides an overview of the use of this modality in pediatrics in order to identify medication choice, discuss post-operative morbidity and mortality, and evaluate impact on overall survival. Four databases were searched including Scopus, PubMed, Embase, and CINAHL and ultimately 37 papers documenting the use of this modality comprising 264 pediatric patients were included. Malignancies treated include desmoplastic small round cell tumor, rhabdomyosarcoma, angiosarcoma, colorectal carcinoma, and mesothelioma, with several rarer tumor types. Cisplatin was the most commonly used drug for HIPEC at varying concentrations for 30-90 min in duration at temperatures of approximately 41-42 °C. Reported toxicities were generally self-limited and there was no post-operative mortality. The impact on overall survival versus systemic chemotherapy and debulking surgery is uncertain due to lack of clinical trials and very small sample size across tumor subsets and the overall pediatric population. The relationship between degree of tumor burden and extent of surgical debulking needs to be further clarified. Future directions include prospective clinical trials, establishment of patient databases to facilitate standardization of HIPEC in pediatric patients, and additional approaches to optimize HIPEC.

National Practice Patterns in Malignant Peritoneal Mesothelioma: Updates in Management and Survival.

Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted. Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival. Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment. CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.

Abstract CT122: A phase 1/2 open-label, multicenter, dose escalation and expansion study of AVB-001, an intraperitoneally administered, cell-generated, human IL-2 immunotherapy in patients with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube

Abstract Background: The potential of cytokines as cancer therapeutics has been limited by short half-life and severe adverse effects associated with high systemic exposure when delivered intravenously. Many strategies are being explored to overcome these limitations. A locoregional delivery approach to achieve high sustained local concentrations in the tumor microenvironment with minimal systemic exposure could widen the therapeutic window. Early experience with free recombinant human IL2 (rhIL-2) given intraperitoneally (IP) showed meaningful clinical activity in relapsed ovarian cancer. Still, the cumbersome delivery procedure requiring indwelling catheters and need for high volume IP infusions leading to frequent complications and poor patient compliance limited the utility of this approach. To overcome these shortcomings, we developed a clinically translatable localized delivery LOCOcyteTM platform composed of polymer encapsulated allogeneic epithelial cells engineered to produce immune effector molecules for local delivery with temporal regulation. The first product, AVB-001, produces native hIL-2, for the treatment of ovarian cancer and other peritoneal malignancies. IP AVB-001 inhibited tumor growth and improved survival in an in vivo ID8 ovarian cancer murine model. Sustained IL-2 production with well tolerated high IP concentrations were achieved, with &amp;gt;100x differential concentration vs. systemic blood levels in both mice and non-human primates. Strong local and systemic immune activating effects, optimized T cell profile and immune memory were observed without concomitant increase of T regs. The first in human study of AVB-001 in patients with advanced ovarian cancer (NCT05538624) is described here. Methods: Part 1 dose escalation exploring 4 ascending dose levels (capsules target production of 0.6, 1.2, 2.4, and 3.6 ug hIL2/kg/d) with a Bayesian Optimal Interval 3+3 design, in patients with recurrent high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube. A minimum of 12 and up to 24 patients will be enrolled to receive one dose of AVB-001 administered IP. The primary objective is to evaluate safety (Incidence and severity of adverse events per NCI CTCAE v5.0), tolerability, and feasibility of delivering AVB-001 IP, and establish the RP2D. Secondary objectives include assessment of antitumor activity (RECIST v1.1, iRECIST), pharmacokinetics, and pharmacodynamic correlates of immune activation. Part 2 will enroll 20 patients at the RP2D with efficacy as the primary objective. This multicenter study will be conducted at 5 sites, currently one site is open. The first patient was dosed in December 2022. Recruitment in dose level 1 cohort continues. Citation Format: Shannon N. Westin, Travis Sims, Karen Andreas, Eric Soliman, Manish Jain, Claudio A. Dansky Ullmann, Amir A. Jazaeri. A phase 1/2 open-label, multicenter, dose escalation and expansion study of AVB-001, an intraperitoneally administered, cell-generated, human IL-2 immunotherapy in patients with platinum-resistant, high-grade, serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT122.

MP53-01 TOXICITY OF CYTOREDUCTIVE SURGERY AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC) IN PEDIATRIC PATIENTS WITH RHABDOMYOSARCOMA: EARLY EXPERIENCE AND RESULTS OF A PHASE 1 TRIAL

You have accessJournal of UrologyCME1 Apr 2023MP53-01 TOXICITY OF CYTOREDUCTIVE SURGERY AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY (HIPEC) IN PEDIATRIC PATIENTS WITH RHABDOMYOSARCOMA: EARLY EXPERIENCE AND RESULTS OF A PHASE 1 TRIAL Andres Guillen Lozoya, Alexander Krueger, Candace Granberg, and Patricio Gargollo Andres Guillen LozoyaAndres Guillen Lozoya More articles by this author , Alexander KruegerAlexander Krueger More articles by this author , Candace GranbergCandace Granberg More articles by this author , and Patricio GargolloPatricio Gargollo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Soft-tissue sarcomas as a group comprise the most common type of extra-cranial solid tumor type in children. Most soft-tissue sarcomas diagnosed in children are rhabdomyosarcoma (RMS). Rapid growth and aggressive metastatic spread are major factors in severely decreasing the prognosis of patients with this condition, and current therapies for recurrence of intraperitoneal malignancies have not provided an increase in survival over several decades. HIPEC has been demonstrated to improve survival in several adult peritoneal malignancies. Similarly, in children cytoreduction and HIPEC have been applied to some pediatric malignancies with promising results. We aim to evaluate toxicities of pediatric RMS patients treated with continuous perfusion of hyperthermic intraperitoneal cisplatin+doxorubicin. METHODS: This is a single-arm feasibility and safety study. Pediatric patients with resectable primary refractory or recurrent intra-abdominal RMS tumors treated with HIPEC (CIS+DOXO) from June of 2019 to June of 2022 were included in the analysis. Patients with mets not limited to peritoneum, prior HIPEC, active infection or systemic illness were excluded from the study. Clinical and demographic variables, adverse events within 30 days post-Op, recurrence free survival (RFS) and overall survival (OS) were compiled and stratified. RESULTS: A total of n=6 participants were included in the analysis. The cohort was comprised mostly of female patients (83%), Bladder was the most common primary tumor location (50%) and Embryonal was the most common subtype (83%). Median OS of the cohort was 20.4±6.6 months, non-deceased patients have had a median survival of 36±7.5 months and mean RFS of 14 months. 50% of the cohort evolve without a grade ≥3 adverse event [CTCAE v4]. Table 1 CONCLUSIONS: We conclude that the study technique is reasonably well tolerated in pediatric patients with refractory or recurrent intra-abdominal RMS tumors. The efficacy of Cytoreductive Surgery and HIPEC in pediatric RMS patients needs further evaluation with a larger cohort of patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e712 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andres Guillen Lozoya More articles by this author Alexander Krueger More articles by this author Candace Granberg More articles by this author Patricio Gargollo More articles by this author Expand All Advertisement PDF downloadLoading ...

Imaging Recommendations for Diagnosis, Staging, and Management of Peritoneal Malignancies

AbstractPeritoneum is a serosal membrane lining the solid viscera and the hollow viscus of the abdomen and is made of a single layer of mesothelial cells. The most common primaries that spread to the peritoneum include gastrointestinal, ovarian, colorectal, and peritoneal metastases can be seen at some point during the disease course in 15 to 43%, 60 to 70% and 15 to 20% of patients, respectively. Other malignancies involving the peritoneum such as primary peritoneal carcinoma, peritoneal mesothelioma, peritoneal lymphomatosis, pseudomyxoma peritonei from low-grade appendiceal mucinous neoplasm, are far less common. The review strives to provide a framework for diagnosis and management of the disease.

Mesothelioma In Situ Mimicking Well-differentiated Papillary Mesothelial Tumor.

We have previously hypothesized that well-differentiated papillary mesothelial tumor (WDPMT) consists of 2 morphologically identical lesions, one of which is true WDPMT, while the other is a form of mesothelioma in situ. Here, we report 8 examples of the latter phenomenon, 3 with pleural disease (2 men/1 woman, ages 66 to 78y); and 5 with peritoneal disease (all women, ages 31 to 81y). At presentation the pleural cases all had effusions but no evidence of pleural tumor on imaging. Four of the 5 peritoneal cases had ascites as the initial finding and all 4 had nodular lesions that by imaging and/or direct inspection were thought to represent a diffuse peritoneal malignancy. The fifth peritoneal case presented with an umbilical mass. Microscopically, the pleural and peritoneal lesions looked like diffuse WDPMT, but all had lost BAP1. Occasional microscopic foci of superficial invasion were present in 3/3 pleural cases, while single nodules of invasive mesothelioma and/or occasional foci of superficial microscopic invasion were found in all of the peritoneal cases. The pleural tumor patients developed what clinically appeared to be invasive mesothelioma at 45, 69, and 94 months. Four/five peritoneal tumor patients underwent cytoreductive surgery and heated intraperitoneal chemotherapy. Three with follow-up data are alive without recurrence at 6, 24, and 36 months; 1 patient refused treatment but is alive at 24 months. We conclude that mesothelioma in situ morphologically mimicking WDPMT is strongly associated with the synchronous or metachronous development of invasive mesothelioma, but that these lesions appear to progress very slowly.

Diagnostic and Therapeutic Algorithm for Appendiceal Tumors and Pseudomyxoma Peritonei: A Consensus of the Peritoneal Malignancies Oncoteam of the Italian Society of Surgical Oncology (SICO).

Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.

Diagnostic value of positron emission tomography/computed tomography (PET/CT) in detection of peritoneal carcinomatosis

BackgroundThe diagnosis of peritoneal carcinomatosis is challenging and can be difficult to detect with imaging, especially the detection of small-sized peritoneal lesions. The presence of peritoneal neoplastic spread alters tumour staging and is one of the most significant prognostic indicators in several malignancies, and the purpose of this study was to highlight the diagnostic value of PET/CT in detection of peritoneal carcinomatosis in patients with malignant neoplastic disease.ResultsPET/CT has 76.2% sensitivity, 88.9% specificity, 94.1% PPV, 61.5% NPV and 80% accuracy in detection of peritoneal carcinomatosis. Different patterns of FDG uptake of peritoneal carcinomatosis were found such as focal nodular uptake, diffuse abdominal uptake and liver surface focal or diffuse uptake. From all these different patterns, focal nodular uptake was the most frequent pattern. The best cut-off value of SUVmax was 5 for diagnosis.ConclusionsThe study affirms the significant role of PET/CT in the diagnosis of peritoneal carcinomatosis and its important value in the staging, management and follow-up of patients with secondary peritoneal malignancies, especially in case of unavailable or inappropriate peritoneal biopsy. Therefore, PET/CT could help reduce the number of laparotomies and a better selection of patients who are candidates for adjuvant chemotherapy.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignant tumors in children: Initial experience in a single institution.

Peritoneal malignant tumors in children are rare but commonly associated with disease progression and poor outcome. The successful treatment experience of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in adult peritoneal carcinoma has been applied to pediatric peritoneal malignancy in recent years. However, patients with desmoplastic small round cell tumor (DSRCT) accounted for the majority of patients treated with CRS and HIPEC in previous studies. The role of CRS and HIPEC remains controversial due to the rarity of the disease and the limited sample size of studies. Additionally, the cases using CRS and HIPEC except DSRCT were mainly small case reports with unclear outcomes. We present our experience in the treatment of pediatric peritoneal malignancies using CRS and HIPEC, with more emphasis on the safety, feasibility, and short-term outcome. A retrospective query from December 2019 to February 2022 identified 19 children with peritoneal malignancies who underwent CRS and HIPEC in our institution. Clinical characteristics, therapies, and outcomes were summarized and analyzed. The median age of the patients was 6.4 years (range, 0.7-13.9 years). The histologic types included rhabdomyosarcoma (7), Wilms tumor (2), clear cell sarcoma of the kidney (2), undifferentiated sarcoma (2), immature teratoma (1), peritoneal serous carcinoma (1), malignant rhabdoid of the kidney (1), malignant germ cell tumor (1), neuroblastoma (1), and epithelioid inflammatory myofibroblast sarcoma (1). Seven patients underwent initial operation, and 12 patients received reoperation for tumor recurrence. The median peritoneal carcinomatosis index was 5 (range, 2-21). There were no perioperative deaths or life-threatening complications of CRS and HIPEC. Two patients had grade 3 complications of wound infection and wound dehiscence. With a median follow-up time of 14 months (range, 1.5-31 months), 14 patients were alive, and 5 died of tumor recurrence. Of the 14 patients who were alive, 2 relapsed after CRS and HIPEC and then received radiotherapy and molecular-targeted therapy or chemotherapy. CRS and HIPEC are safe and feasible in children, without increasing serious complications in the peri- and postoperative periods. The complication is acceptable. The short-term outcome shows possible effectiveness in pediatric peritoneal malignant tumors. The long-term effectiveness needs to be verified by additional cases and long-term follow-ups.

Therapie peritonealer Metastasen

BackgroundPeritoneal carcinomatosis arising from gastrointestinal malignancies represents a major therapeutic challenge for oncological surgeons, oncologists and radiotherapists. The development of so-called multimodal therapy consisting of perioperative systemic chemotherapy, radical cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy (HIPEC) has resulted in significant prolongation of overall survival in these patients.AimSurvival data from prospective, randomized trials and register studies in recent years have established multimodal therapy as a treatment option for peritoneal metastatic colorectal as well as gastric cancer in the German guidelines. The current work on this complex topic ensures insight into the background of this topic.Materials and methodsThis paper is based on a selective literature search in the medical database PubMed on the keywords hyperthermic intraperitoneal chemotherapy, colorectal cancer, gastric cancer, multimodal therapy as well as on internal data from a reference center for the therapy of peritoneal malignancies from Germany.ResultsMultimodal therapy consisting of perioperative systemic chemotherapy, radical cytoreductive surgery, and HIPEC leads to better oncologic outcome in well-selected patients with peritoneal metastatic gastric and colorectal cancer in high-volume centers.

DIFFUSE ECTOPIC DECIDUOSIS MIMICKING AS PERITONEAL CARCINOMATOSIS: A CASE REPORT OF A YOUNG FEMALE WITH MULTIPLE SEROSAL AND OMENTAL NODULES FOUND DURING A CAESARIAN SECTION

Background &amp; Objectives: Ectopic deciduosis refers to an abnormal occurrence of decidual tissue beyond the endometrium, predominantly on the surface of the uterus, fallopian tubes, ovaries and omentum. Diffuse omental and perito-neal involvement is a perplexing manifestation that may mimic peritoneal carcinomatosis. It is not accompanied by any symptoms and complications in most of the cases and does not require treatment. However, rarely it can present with acute abdomen or imitate peritoneal malignancy and, thus, associated with diagnostic difficulties and unnecessary interventions. Aim of this case report is to describe a rare case of peritoneal deciduosis in a young female, found incidentally, during a caesarean section, mimicking metastatic nodules. Afutile hysterec-tomy along with omentectomy was performed.&#x0D; Methods: A case of diffuse ectopic deciduosis mimicking as peritoneal carcinomatosis in a 29 years young female with full term pregnancy was found during a lower segment caesarian section, undertaken in a tertiary care teaching hospital of Lahore, Pakistan. The histopathological diagnosis was based on common technique of paraffin embedding and hematoxylin-eosin staining along with ancillary immune-histochemical evaluation.&#x0D; Results: Histopathological evaluation showed ectopic decidual tissue consisted of solid nests and loosely cohesive aggregates; large polygonal cells with abundant granular eosinophilic cytoplasm; sharply defined cell borders, bland nuclei with dispersed chromatin and single conspicuous nucleoli on the surface of uterus and in omental fat. Weak staining for CD30 was observed in the decidual cell cytoplasm and negative staining for CK and Calretinin in decidual cells was found. Calretinin and CK highlight benign mesothelial cells and help to rule out differentials of mesothelioma and metastatic carcinoma.&#x0D; Conclusion: Peritoneal deciduosis represents a rare entity and it is important to consider this condition in patients, especially in pregnant women, to prevent unnecessary intervention In addition, distinguishing this condition from malignant neoplasms will help in deciding correct treatment options.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Methodology.

A group of experts from the Peritoneal Surface Oncology Group International (PSOGI) and the BIG-RENAPE group carried out a consensus among surgeons experienced in treating peritoneal malignancies from around the world to derive recommendations on indications of hyperthermic intraperitoneal chemotherapy (HIPEC), choice and details of HIPEC regimens, and areas for future research. This manuscript describes the methodology of achieving this consensus and the degree of participation of experts. The Delphi technique was used and the questionnaire comprised three categories: evidence-based recommendations using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) system with the PICO (patient, intervention, comparison, and outcome) method, an opinion survey, and research recommendations. A consensus was achieved if any one option had >50% of votes, or positive or negative recommendations combined had > 70% of votes. Of the 145 experts solicited, 71.1% in round I and 72.2% in round II took the survey. Participation was highest among surgeons treating both gastrointestinal and gynecological malignancies. Of 113 questions, after round I, a consensus was achieved for 72 (63.7%) questions, and after the second round, consensus was achieved for another 22 (19.4%) questions, making a total of 94 (83.1%) questions for which a consensus was achieved. This consensus was carried out using a thorough review of literature and robust rating of evidence, and included key experts and opinion leaders from across the world. The results could guide clinicians on the use of HIPEC, both in their day-to-day clinical practice and in designing clinical trials.

Re-do cytoreductive surgery with hyperthermic intra-peritoneal chemotherapy (HIPEC): Risk factors and complications.

An effective multi-modal treatment option for patients with peritoneal surface metastatic malignancies has progressed and developed over the decades as cytoreductive surgery (CRS), and hyperthermic intra-peritoneal chemotherapy (HIPEC) delivers highly concentrated, heated chemotherapy drugs directly to the abdomen during surgery. Peritoneal metastasis and high staging abdominal malignancies were considered incurable and end up with the palliation only; the CRS+HIPEC combination approach increases the median survival rate and gives a better quality of life to these patients. It is a complicated surgery which poses a high rate of complications and challenges which are difficult to manage and requires a multi-disciplinary approach. The aim of this study is to elaborate the perioperative possible physiological changes, risk factors, and related complications after re-do HIPEC.

Diagnosis and treatment of peritoneal carcinomatosis - a comprehensive overview.

Peritoneal carcinomatosis, which is the most common malignant process of the peritoneal cavity, originates mostly from colorectal, gastric, and gynaecological malignancies. The differential diagnosis is broad and covers primary peritoneal malignancies, as well as many benign disorders such as endometriosis, and inflammatory and infectious diseases. Peritoneal implants tend to locate in the areas of the physiological stasis of the peritoneal fluid: pelvic peritoneal reflections, right and left paracolic gutters, superior part of the sigmoid mesocolon, ileocolic area, and the right subdiaphragmatic space. The 3 most common imaging findings are ascites, nodular implants, and infiltration of the peritoneal fatty tissue. Several imaging modalities may be applied in patients with peritoneal carcinomatosis. Ultrasound has low sensitivity and specificity, and therefore plays only a marginal role. Computed tomography is the method of choice, due to its availability, cost-effectiveness, and relatively high sensitivity. The sensitivity of magnetic resonance imaging depends on the size of peritoneal implants - in cases of implants larger than 10 mm is comparable to CT. Some studies suggest that PET/CT may be the most sensitive method, yet its usefulness in everyday practice is controversial. The Peritoneal Carcinomatosis Index (PCI) is a scale used to assess the tumour burden in the peritoneum and may serve as a communication tool between clinicians and radiologists. The imaging findings may influence the surgeon's decision on performing cytoreductive surgery, which may be followed by intraperitoneal chemotherapy (HIPEC or EPIC procedures). The introduction of these therapeutic methods has significantly improved the life expectancy of patients with peritoneal carcinomatosis.

Extensive Peritonectomy is an Independent Risk Factor for Cisplatin HIPEC-Induced Acute Kidney Injury

BackgroundCisplatin (CDDP)-containing hyperthermic intraperitoneal chemotherapy (HIPEC) is frequently applied in selected patients with peritoneal malignancies derived from ovarian cancer, gastric cancer, and primary peritoneal mesothelioma. HIPEC with CDDP increases perioperative morbidity, in particular by inducing acute kidney injury (AKI). Factors contributing to occurrence of AKI after intraperitoneal perfusion with CDDP have not been sufficiently evaluated.Patients and MethodsData from 63 patients treated with a CDDP-containing HIPEC regimen were retrospectively analyzed concerning demographics, underlying disease, surgery, and HIPEC details to evaluate risk factors of AKI. A preclinical rat perfusion model was applied to assess the influence of temperature, concentration, perfusate volume, perfusion flow rate, and extent of peritonectomy on drug absorption upon intraperitoneal CDDP perfusion.ResultsAKI occurred in 66.1% of patients undergoing CDDP-containing HIPEC, with total intraoperative fluid influx being a negative and the extent of parietal peritonectomy being a positive independent predictor of postoperative AKI. In a preclinical model, bilateral anterior parietal peritonectomy significantly increased systemic CDDP absorption by 1.6 to 2-fold. CDDP plasma levels in animals were significantly higher after both perfusion with increased CDDP perfusate concentrations and bilateral anterior parietal peritonectomy.ConclusionCDDP-containing HIPEC is associated with relevant morbidity owing to its systemic toxicity. Extent of parietal peritonectomy is an independent predictor of AKI. CDDP dose reduction should be considered in case of extensive parietal peritonectomy. Cytostatic drug concentrations in HIPEC perfusate should be paid more attention to than total dose per body surface area. Further clinical studies are needed to confirm the presented preclinical findings.