Search Results (17)

Background: This study aimed to analyze the morbidity, mortality, and survival outcomes in patients with peritoneal surface malignancies who were initially considered candidates for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) but were found to have unresectable disease, resulting in nontherapeutic exploratory laparotomy. Patients and Methods: We evaluated data from our referral center for the treatment of peritoneal surface malignancies between January 2008 and December 2022. Adverse events following nontherapeutic laparotomy were classified using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Results: Among a cohort of 486 patients with peritoneal surface malignancies initially considered candidates for CRS + HIPEC, 46 cases (9.4%) were aborted due to the disease being deemed unresectable during exploratory laparotomy. The primary reasons for unresectability included extensive disease spread, observed in 28 patients, with massive small intestine involvement detected in 13 of these cases. The median duration of surgery was 90 min (range: 60–180 min). Postoperative complications occurred in 10 patients (22%), with a mortality rate of 4.3% (2 patients). Survival was significantly lower in patients who did not receive adjuvant systemic chemotherapy with palliative intent (4 months vs. 15 months, p < 0.01). Conclusions: Exploratory laparotomy in patients with peritoneal surface malignancies considered for CRS with HIPEC carries a substantial risk of complications. Improved preoperative staging using advanced technologies such as radiomics and laparoscopy is expected to reduce the number of patients undergoing nontherapeutic laparotomy. Full article

Background: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) using the original 30 min protocol has shown limited benefits in patients with peritoneal metastasis of colorectal cancer (PMCRC), likely due to the short duration, which limits drug penetration into tumor nodules. Bevacizumab, an antiangiogenic antibody that modifies the tumor microenvironment, may improve drug delivery during HIPEC. This in silico study evaluates the availability of oxaliplatin within tumor nodules when HIPEC is performed after bevacizumab treatment. Methods: Using a computational fluid dynamics (CFD) model of HIPEC, the temperature and oxaliplatin distribution within the rat abdomen were calculated, followed by a model of drug transport within tumor nodules located at various sites in the peritoneum. The vascular normalization effect of the bevacizumab treatment was incorporated by adjusting the biophysical parameters of the tumor nodules. The effective penetration depth values, including the thermal enhancement ratio of cytotoxicity, were then compared between HIPEC alone and HIPEC combined with the bevacizumab treatment. Results: After bevacizumab treatments at doses of 0.5 mg/kg and 5 mg/kg, the oxaliplatin availability increased by up to 20% and 45% when HIPEC was performed during the vascular normalization phase, with the penetration depth increasing by 1.5-fold and 2.3-fold, respectively. Tumors with lower collagen densities and larger vascular pore sizes showed higher oxaliplatin enhancement after the combined treatment. Bevacizumab also enabled a reduction in the oxaliplatin dose (up to half at 5 mg/kg bevacizumab) while maintaining effective drug levels in the tumor nodules, potentially reducing systemic toxicity. Conclusions: These findings suggest that administering oxaliplatin-based HIPEC during bevacizumab-induced vascular normalization could significantly improve drug penetration and enhance treatment efficacy. Full article

Introduction: Cytoreductive surgery (CRS) coupled with hyperthermic intraperitoneal chemotherapy (HIPEC) is a potentially curative approach to peritoneal disease (PD) and corresponds to the needs of patients with dire survival rates. However, the oncological community remains cautious toward this procedure because of its significant morbidity and mortality rates. This evolving evidence around CRS and HIPEC and its impact suggests a need for more standardized procedures in existing centers. Because of its complexity and potential for high morbidity and mortality, critical observation of our center’s complication rates using complication management documentation tools were crucial to further develop our standard operating procedures (SOP) and maximize patient safety. Methods: Our prospectively maintained institutional database was queried to identify all patients who underwent CRS and HIPEC and had a filled-out quality management (QM) and complication management documentation tool at discharge at the surgical department of the Charité—Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany, between January 2018 and December 2023. Results: A total of 155 patients had a surgical and/or medical complication recorded. In total, 305 surgeries were surveyed. Some patients had more than one postoperative complication; hence, 344 events in 50 categories were recorded, of which 267 were graded 3a or higher in 92 patients. The most common medical complications were of pulmonary and renal origin. On the surgical side, surgical site infections (SSI) were most common. The incidence of anastomotic leakage (AL) was 5% (n = 8), with no events between 2021 and the present. Patients with longer surgery duration times were at higher risk for developing postoperative complications. Conclusions: Major abdominal surgeries like CRS and HIPEC are associated with significant patient morbidity despite achieving optimal oncological outcomes. Postoperative complications are managed through strict surveillance and transparency, particularly in our large reference centers, to minimize patient risk. Quality management programs in our department have successfully maintained high standards of care without compromising patient safety. Full article

This study investigated miRNA and cytokine expression changes in peritoneal fluid samples of patients with advanced ovarian cancer (OVCA) after receiving hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreduction surgery (CRS). We collected samples prior to HIPEC, immediately after HIPEC, and 24/48/72 h after CRS from a total of 6 patients. Cytokine levels were assessed using a multiplex cytokine array, and a miRNA PanelChip Analysis System was used for miRNA detection. Following HIPEC, miR-320a-3p, and miR-663-a were found to be immediately down-regulated but increased after 24 h. Further, significant upregulation post-HIPEC and sustained increases in expression were detected in six other miRNAs, including miR-1290, miR-1972, miR-1254, miR-483-5p, miR-574-3p, and miR-574-5p. We also found significantly increased expression of cytokines, including MCP-1, IL-6, IL-6sR, TIMP-1, RANTES, and G-CSF. The changing expression pattern throughout the study duration included a negative correlation in miR-320a-3p and miR-663-a to cytokines including RANTES, TIMP-1, and IL-6 but a positive correlation in miRNAs to cytokines including MCP-1, IL-6sR, and G-CSF. Our study found miRNAs and cytokines in the peritoneal fluid of OVCA patients demonstrated different expression characteristics following CRS and HIPEC. Both changes in expression demonstrated correlations, but the role of HIPEC remains unknown, prompting the need for research in the future. Full article

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. Full article

Background: Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and by the extent of the disease. Methods: Prognostic relevance of tumor markers CA19-9 and CEA, gender, Peritoneal Cancer Index (PCI), and completeness of cytoreduction (CC) after cytoreductive surgery were evaluated on 193 consecutive PMP patients, based on a retrospective analysis of prospectively gathered data from a German tertial referral center. Results: We demonstrated that low PCI, CC0 status, low-grade histology, and female gender were independent positive prognostic factors for both overall survival (OS) and progression-free survival (PFS). Furthermore, LAMN patients with achieved CC0 status show significantly better OS and PFS compared to those with CC1 status (p = 0.0353 and p = 0.0026 respectively). In contrast, the duration and drug of hyperthermic intraperitoneal chemotherapy (HIPEC) were not prognostic in any comparison. Increased CA19-9 and CEA levels were significantly associated with HAMN cases, but also predicted recurrence in patients with low-grade histologies. Conclusion: Our study confirmed the prognostic role of tumor markers and emphasized the importance of CC status and PCI in a large cohort of PMP- and LAMN patients. Full article

The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers. Full article

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has gained increasing acceptance in clinical practice. Performing CRS and HIPEC laparoscopically represents a challenging and intriguing technical evolution. However, the experiences are limited, and the evidence is low. This retrospective analysis was performed on patients treated with laparoscopic CRS-HIPEC within the Italian Peritoneal Surface Malignancies Oncoteam. Clinical, perioperative, and follow-up data were extracted and collected on prospectively maintained databases. We added a systematic review according to the PRISMA method for English-language articles through April 2022 using the keywords laparoscopic, hyperthermic, HIPEC, and chemotherapy. From 2016 to 2022, fourteen patients were treated with Lap-CRS-HIPEC with curative intent within the Italian centers. No conversion to open was observed. The median duration of surgery was 487.5 min. The median Peritoneal Cancer Index (PCI) was 3, and complete cytoreduction was achieved in all patients. Two patients (14.3%) had major postoperative complications, one requiring reintervention. After a median follow-up of 16.9 months, eleven patients were alive without disease (78.6%), two patients developed recurrence (14.3%), and one patient died for unrelated causes (7.1%). The literature review confirmed these results. In conclusion, current evidence shows that Lap-CRS-HIPEC is feasible, safe, and associated with a favorable outcome in selected patients. An accurate patient selection will continue to be paramount in choosing this treatment. Full article

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a treatment option for peritoneal metastases (PM) but is associated with significant postoperative morbidity. The aim of this study was to determine the prognostic value of computed tomographic (CT)-measured sarcopenia on postoperative outcomes and survival in patients undergoing CRS-HIPEC for PM from various origins. A retrospective cohort study was conducted between 2012 and 2020. Three-hundred and twelve patients (mean age 57.6 ± 10.3, 34.3% male) were included, of which 88 (28.2%) were sarcopenic. PM from a colorectal origin was the most common in both groups. The proportion of major postoperative complications (Clavien-Dindo ≥ III) was not higher in the sarcopenic group (15.9% in sarcopenic patients vs. 23.2% in nonsarcopenic patients, p = 0.17). The mean Comprehensive Complication Index scores, HIPEC-related toxicities, length of hospital stay, and duration of parenteral nutrition were comparable regardless of sarcopenia status. In the multivariate logistic regression analysis of severe complications, only peritoneal carcinomatosis index reached statistical significance (OR, 1.05; 95% CI, 1.01 to 1.08, p = 0.007). Sarcopenia did not impact origin-specific overall survival on Cox regression analysis. Sarcopenia was not associated with worse rates of postoperative severe complications or worse survival rates. Future prospective studies are required before considering sarcopenia as part of preoperative risk assessment. Full article

Background: The usage of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gynecological cancers is increasing. Methods: Prospectively collected data of 85 advanced primary ovarian/fallopian tube cancer and peritoneal carcinoma patients of a single center were investigated. Results: A total 48, 37, 62, and 25 patients were enrolled into the HIPEC with/without neoadjuvant chemotherapy (upfront vs. interval) and into the 60 min and 90 min long HIPEC groups, respectively. Better overall survival (OS) was observed in the 90 min HIPEC group (p = 0.0330), compared to the 60 min HIPEC group. Neither OS (p = 0. 2410), disease-specific (p = 0. 3670), nor recurrence-free survival (p = 0.8240) differed between upfront and interval HIPEC. Higher peritoneal carcinomatosis index (PCI) values were associated with worse disease-specific survival (p = 0.0724). Age (p = 0.0416), body mass index (p = 0.0044), PCI (p < 0.0001), the type (p = 0.0016) and duration (p = 0.0012) of HIPEC, and increased perioperative morbidity (p < 0.0041) had the greatest impact on OS. Conclusions: Increasing data support the value of HIPEC in the treatment of advanced ovarian cancer. Ongoing prospective studies will definitively clarify the role and timing of this additional therapeutic approach. Full article

(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms “intraperitoneal chemotherapy AND gastric cancer”. Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50–200 mg/m² cisplatinum and 30–40 mg/m² mytomycin C at 42–43 °C for 60–90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties. Full article

Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term “morbidity” should be defined more clearly by the authors. Full article

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments. Full article

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) is used for treating peritoneal metastases of various origins. Present HIPEC protocols have rarely been validated for relevant parameters such as optimal agent, duration and perfusate temperature. In vitro experiments are not completely representative of clinical circumstances. Therefore, a good preclinical in vivo HIPEC model is needed in which temperature distributions can be well-controlled and are stable throughout treatments. Methods: We designed a setup able to generate and maintain a homogeneous flow during a 90-min HIPEC procedure using our in-house developed treatment planning tools and computer aided design (CAD) techniques. Twelve rats were treated with heated phosphate-buffered saline (PBS) using two catheter setups (one vs. four- inflows) and extensive thermometry. Simulated and measured thermal distribution and core temperatures were evaluated for the different setups. Results: Overall, the four-inflow resulted in more stable and more homogeneous thermal distributions than the one-inflow, with lower standard deviations (0.79 °C vs. 1.41 °C at the outflow, respectively) and less thermal losses. The average thermal loss was 0.4 °C lower for rats treated with the four-inflow setup. Rat core temperatures were kept stable using occasional tail cooling, and rarely exceeded 39 °C. Conclusion: Increasing the number of inflow catheters from one to four resulted in increased flow and temperature homogeneity and stability. Tail cooling is an adequate technique to prevent rats from overheating during 90-min treatments. This validated design can improve accuracy in future in vivo experiments investigating the impact of relevant parameters on the efficacy of different HIPEC protocols. Full article

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a curative treatment option for patients with peritoneal carcinomatosis. Total pelvic exenteration (TPE) is an established treatment option for locally advanced pelvic malignancy. These two procedures have high mortality and morbidity, and therefore, their combination is not currently recommended. Herein, we reported our experience on TPE associated with CRS/HIPEC with a critical analysis for rectal cancer with associate peritoneal metastases. Methods: From March 2006 to August 2020, 319 patients underwent a CRS/HIPEC in our hospital. Among them, 16 (12 men and four women) underwent an associated TPE. The primary endpoints were perioperative morbidity and mortality. Results: There was locally recurrent rectal cancer in nine cases, six locally advanced primary rectal cancer, and a recurrent appendiceal adenocarcinoma. The median Peritoneal Cancer Index (PCI) was 8. (4–16). Mean duration of the surgical procedure was 596 min (420–840). Complete cytoreduction (CC0) was achieved in all patients, while clear resection (R0) margins on the resected pelvic organs were achieved in 81.2% of cases. The median hospital stay was 46 days (26–129), and nine patients (56.2%) experienced severe complications (grade III to V) that led to death in two cases (12.5%). The total reoperation rate for patients was 6/16 (37.5%) and 3/16 (18.75%) with percutaneous radiological-guided drainage. Conclusions: In summary, TPE/extended TPE (ETPE) associated with CRS/HIPEC may be a reasonable procedure in selected patients at expert centers. Pelvic involvement should not be considered a definitive contraindication for CRS/HIPEC in patients with resectable peritoneal surface diseases if a R0 resection could be achieved on all sites. However, the morbidity and the mortality are high with this combination of treatment, and further research is needed to assess the oncologic benefit and quality of life before such a radical approach can be recommended. Full article