Hyperthermic Intraperitoneal Chemotherapy Treatment Research Articles

Analysis of causes and prognostic impact of tube occlusion during hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei

BackgroundAppendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications.MethodsFrom October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments.ResultsTubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion.ConclusionTubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.

In vitro 3D microfluidic peritoneal metastatic colorectal cancer model for testing different oxaliplatin-based HIPEC regimens.

Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an invitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments. We determined the effects of current therapy options using a 3D static disease model on human colon carcinoma cell lines (HCT 116) and transforming growth factor-β1 induced epithelial-to-mesenchymal transition (EMT) HCT 116 lines at 37 °C and 42 °C for 30, 60, and 120 min. We determined oxaliplatin's half maximal inhibitory concentrations in a 3D static culture by using viability assay. Clinical practices of HIPEC were applied in the developed model. EMT-induced HCT 116 cells were less sensitive to oxaliplatin treatment compared to non-induced cells. We observed increased cytotoxicity when increasing the temperature from 37 °C to 42 °C and extending the treatment duration from 30 to 120 min. We found that 200 mg/m2 oxaliplatin administered for 120 min is the most effective HIPEC treatment option within the framework of clinic applications. The tool map provide insights into creating more realistic pre-clinical tools that could be used for a patient-based drug screening.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC): New Approaches and Controversies on the Treatment of Advanced Epithelial Ovarian Cancer-Systematic Review and Meta-Analysis.

Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been extensively studied in patients with peritoneal carcinomatosis, and it holds promise as a therapeutic strategy, but its role remains elusive. The aim of this study was to assess the existing evidence for the use or not of HIPEC in primary debulking surgery (PDS), interval debulking surgery (IDS), and recurrent ovarian cancer (ROC), evaluated in terms of survival rates and post-surgical morbidity. Medline, Pubmed, Cochrane, and Medscape were systematically searched for any article comparing the use of HIPEC treatment with any other therapy in patients with ovarian cancer in PDS, IDS, and ROC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. We only considered English-language published studies. We included 14 studies, including two RCTs with a total of 1813 women, published between 2003 and 2023 with a recruitment period between 1998 and 2020. In PDS, there were no differences in progression-free survival (PFS) between HIPEC and controls [MD -5.53 months [95% CI -19.91 to 8.84 months]; I2 = 96%]. Conversely, in patients treated with NACT, pooled results showed a significant survival advantage in terms of progression-free survival (PFS) and overall survival (OS) in the combined HIPEC plus IDS group rather than surgery alone [PFS: MD 4.68 months (95% CI 3.49 to 5.86 months, I2 = 95%); OS: MD 11.81 months (95% CI 9.34 to 14.27 months); I2 = 97%]. Concerning ROC patients, pooled MD did not show either a significant PFS difference between intervention and controls [MD 2.68 months (95% CI 433 to 9.70 months); I2 = 95%], and OS significant difference (MD 6.69 months [95% CI -9.09 to 22.47 months]; I2 = 98%). Severe post-operative complications (≥grade 3) were available in 10 studies, accounting for 1108 women. Overall, there was a slightly but significantly increased risk with the combined approach compared to controls [RR 1.26 (95% CI 1.02 to 1.55); I2 = 0%]. The combination of HIPEC with cytoreductive surgery prolongs OS and PFS in advanced epithelial ovarian cancer after NACT with acceptable morbidity. However, additional trials are still needed to determine the effectiveness of HIPEC in primary and recurrence settings. In the era of personalized medicine, the correlation between the efficacy of HIPEC and biological and molecular findings represents a challenge for the future of ovarian cancer.

Long-term survival in patients with PMP: a single-institutional retrospective study from China

BackgroundAs the standard treatment for pseudomyxoma peritonei (PMP), cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) can significantly prolong the survival of PMP patients, and some patients can even achieve long-term survival (LTS) or clinical cure. The purpose of this study was to analyze the clinicopathological and treatment features of PMP patients with LTS and to explore the survival benefit factors of PMP patients.MethodsThe clinicopathological and prognostic data of PMP patients who received CRS + HIPEC at our center from December 2004 to May 2023 were retrospectively analyzed. PMP patients were divided into LTS group (≥ 10 years) and short-term survival (STS) group (< 5 years) according to the length of natural history. Univariate and multivariate analyses were performed to explore the beneficial factors of PMP patients with LTS.ResultsA total of 609 patients with PMP received CRS + HIPEC treatment at our center. Two-hundred one patients with PMP were included in the study after screening, including 39 patients (19.4%) in the LTS group and 162 patients (80.6%) in the STS group. In STS group and LTS group, median overall survival based on natural history was 29.2 (2.4–59.9) vs. 138.9 (120.3–416.7) months. Univariate analysis revealed 8 factors (P < 0.05) with statistically significant differences between the two groups: gender, chemotherapy history, previous surgical score, Karnofsky Performance Status score, pathological diagnosis, lymphatic metastasis, peritoneal cancer index, and completeness of cytoreduction (CC). Multivariate analysis identified only two factors independently associated with LTS of PMP patients: CC and pathological diagnosis.ConclusionComplete CRS and pathological features are two key factors affecting LTS in PMP patients.

HIPEC in Ovarian Cancer Is the Future… and Always Will Be? Results from a Spanish Multicentric Survey.

Ovarian cancer is the leading cause of death due to gynecological tumors in the female population. Despite optimal first-line treatment, including cytoreduction and platinum-based systemic chemotherapy, recurrences are frequent. The use of hyperthermic intraperitoneal chemotherapy (HIPEC) has been criticized, especially because of the lack of randomized controlled trials (RCTs) with convincing results to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination. In 2018, the clinical trial published by Van Driel et al. reported improved outcomes in favor of HIPEC treatment with cisplatin. In this study, we conducted a national survey within the Spanish group of peritoneal surgical oncology (Grupo Español de Cirugía Oncológica Peritoneal, GECOP) to explore the impact of the results of this RCT on clinical practice. A total of 33 groups completed the survey. Routine clinical practice was not changed in 28 of the 33 groups (85%) based on the results of the Van Driel trial. Despite the results of this RCT, most groups considered that more RCTs are needed and that, in the future, HIPEC may become the standard of care. In conclusion, the results from RCTs evaluating HIPEC treatment in patients with ovarian cancer has not been transferred to clinical practice.

Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei).

Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.

A case report of low-grade appendiceal mucinous neoplasm in perforated appendicitis: literature review, acute surgery and later additional HIPEC treatment to prevent pseudomixoma peritonei

Low-grade appendiceal mucinous neoplasm (LAMN) accounts less than 0.5% of all gastrointestinal neoplasm. Early stage AMNs are usually incidentally diagnosed on a surgical specimen after appendectomy for acute appendicitis. In this study, we reported a 42-year-old female presented complaining right lower abdominal pain for 3 days. Abdominal US revealed inflamed appendix surrounded by ipo-anechoic area of 3 cm, with increased thickness of near ileus. Intraoperatively a fistula between appendix and terminal ileum was found; for that reason, a right hemicolectomy was performed. Histopathology indicated a low-grade appendiceal mucinous neoplasms (LAMNs). Four months later the patient underwent hyperthermic intraperitoneal chemotherapy (HIPEC) with C-mitomycin and Cisplatin and was followed up for 6 months with no disease progression, confirmed by CT scan. At present there is not a consensus about LAMNs treatment, due to the scarcity of cases. Consensus statement of the Peritoneal Surface Oncology Group published in 2020 seems to be the best guideline available nowadays; Recommendations are provided based on three Delphi voting rounds with GRADE-based questions amongst a panel of 80 worldwide PMP experts. Given the rarity of these pathologies, each clinical case and longer follow up are important. Appropriate surgery-based treatment followed by HIPEC could contribute to the improvement of prognosis and severe outcomes among these patients. In our opinion patients affected by LAMN should receive prophylactic HIPEC treatment in order to achieve the greatest survival benefit even if they run the risk of overtreatment.

Extreme cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of peritoneal metastasis.

It was aimed to define the oncologic concept of "extremeness" in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) to determine morbidity-mortality results and final oncologic outcomes. Prospectively recorded data of 666 patients with peritoneal metastases who had undergone CRS/HIPEC between 2007 and 2020 were analyzed. Patients were divided into two groups as extreme (n= 371) and non-extreme (n= 295). Extreme CRS was defined as resection of ≥5 major organs or creation of ≥2 bowel anastomoses or peritoneal carcinomatosis index (PCI)≥ 15 or re-cytoreductive surgery. More CC-1 or CC-2 cytoreduction (p <.001), increased mortality and morbidity (p <.001), prolonged operative time (p <.001), increased intraoperative erythrocyte suspension (p <.001), albumin (p <.001), fresh frozen plasma (FFP) (p <.001), and post-operative erythrocyte suspension (p <.001) usage were found in the extreme CRS/HIPEC group. Operative time, CC-1 or CC-2 cytoreduction, presence of ostomy, development of infection, and use of intra-operative albumin and FFP were found to be independent prognostic factors in Cox regression analysis. Three and five-year survival rates were significantly lower in the extreme CRS/HIPEC group (p <.001). High-volume peritoneal metastatic disease can be completely resected with extreme cytoreduction in carefully selected patients responsive to chemotherapy. Since the significant morbi-mortality related to the treatment of peritoneal metastasis is a real concern, it should be considered in experienced complex cancer centers that provides relatively better oncological outcomes compared to conventional treatments.

Mechanistic Insights on Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.

Epithelial ovarian cancer is an aggressive disease of the female reproductive system and a leading cause of cancer death in women. Standard of care includes surgery and platinum-based chemotherapy, yet patients continue to experience a high rate of recurrence and metastasis. Hyperthermic intraperitoneal chemotherapy (HIPEC) treatment in highly selective patients extends overall survival by nearly 12 months. The clinical studies are highly supportive of the use of HIPEC in the treatment of ovarian cancer, though the therapeutic approach is limited to academic medical centers. The mechanism underlying HIPEC benefit remains unknown. The efficacy of HIPEC therapy is impacted by several procedural and patient/tumor factors including the timing of surgery, platinum sensitivity, and molecular profiling such as homologous recombination deficiency. The present review aims to provide insight into the mechanistic benefit of HIPEC treatment with a focus on how hyperthermia activates the immune response, induces DNA damage, impairs DNA damage repair pathways, and has a synergistic effect with chemotherapy, with the ultimate outcome of increasing chemosensitivity. Identifying the points of fragility unmasked by HIPEC may provide the key pathways that could be the basis of new therapeutic strategies for ovarian cancer patients.

Colorectal cohort analysis from the Intraperitoneal Chemotherapy After Cytoreductive Surgery for Peritoneal Metastasis (ICARuS) clinical trial.

160 Background: ICARuS is a randomized phase II, multicenter trial to evaluate the relative efficacy of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with mitomycin C vs. Early Postoperative Intraperitoneal Chemotherapy (EPIC) with floxuridine (FUDR), after cytoreductive surgery (CRS), for the treatment of peritoneal metastases (PM) from colorectal (CRC) or appendiceal cancer (AC). PRODIGE7 results failed to demonstrate benefit of HIPEC therapy after complete gross resection of CRC PM, prompting termination of CRC accrual and early cohort analysis. Methods: Patients with isolated, confirmed PM were eligible for 1:1 randomization to CRS plus HIPEC with mitomycin C or CRS plus EPIC with FUDR. Patients were stratified by recent systemic chemotherapy and disease (AC vs. CRC). The trial was originally powered to evaluate 212 patients for a 20% gain in a primary endpoint of 3-year progression free survival (PFS: HR = 1.75). Results: Seventy-five CRC patients were included between 4/2013 and 12/2018 for HIPEC (N = 40) or EPIC (N = 35) treatment. Baseline characteristics were well balanced. After a median follow up of 36 months, the median PFS was 7.7 months (95% CI: 6.3-11.1) in the HIPEC arm and 8.8 months (95% CI: 7.1-21.9) in the EPIC arm, HR = 0.69 (95% CI: 0.42-1.14) p = 0.14. In the 42 left-sided primary cancers, the median PFS was 8.4 months (95% CI: 6.4-17.7) in the HIPEC arm and 12.5 months (95% CI: 8.1-NR) in the EPIC arm, HR = 0.60 (95% CI: 0.29-1.22) p = 0.14. In the 33 right-sided primary cancers, the median PFS was 6.5 months (95% CI: 5.5-14.1) in the HIPEC arm and 8 months (95% CI: 5.8-24.1) in the EPIC arm, HR = 0.80 (95% CI: 0.39-1.64) p = 0.53. PFS was significantly better in the EPIC arm among patients with BRAF wildtype (WT) tumors and patients with higher PM burden (PCI &gt; 7). There was no difference between HIPEC and EPIC in the primary toxicity endpoint of complications grade 3 or above (23 vs. 34%, p = 0.3). Conclusions: Three-year PFS did not significantly differ between treatment arms. The lack of survival benefit of HIPEC in the entire cohort and in subset analysis is consistent with the findings of PRODIGE7. ICARuS remains open to accrual for AC. These data support further investigation of the potential benefit of EPIC with CRS in carefully selected patients with CRC PM. Clinical trial information: NCT01815359 .

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Young Patients With Peritoneal Metastasis of Colorectal Cancer—An Asian Experience

IntroductionCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are accepted treatment options for patients with cancers associated with the abdominal region. Currently, there are insufficient data that evaluate the effectiveness of these therapeutic options in young patients who have peritoneal metastasis (PM) originating from colorectal cancer. MethodsIn this investigation, we evaluated perioperative data, clinicopathological manifestations, and survival consequences in 46 younger (≤50 y) patients who underwent CRS and HIPEC therapy between 2017 June and 2019 June and then compared these data with 94 older patients (aged >50 y). ResultsCompared with older patients, younger patients had a higher synchronous PM incidence (78.3% versus 51.1%, P < 0.001) and were more likely to exhibit signet ring histology and mucinous (29.8% versus 60.9%; P < 0.001). The cancer-specific survival rates after CRS and HIPEC treatment were similar in both age sets. Multivariate Cox regression revealed that mucinous/signet adenocarcinoma (hazard ratio 2.20, 95% confidence interval 1.02-4.74; P = 0.044) and rectal origin (hazard ratio 2.51, 95% confidence interval 1.11-5.67; P = 0.027) were independent risk factors for a lower cancer-specific survival rate. ConclusionsYounger (age ≤50 y) patients who have PM of colorectal cancer origin often present synchronous PM, which is less commonly observed in older patients. Tumors in younger patients are more aggressive; however, post-CRS and HIPEC treatment, the benefits are similar to those observed in older cohorts.

Hyperthermic intraperitoneal chemotherapy for patients with gastric cancer based on laboratory tests is safe: a single Chinese center analysis

PurposeAbout 15%—40% of gastric cancer patients have peritoneal metastasis, which leads to poor prognosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is considered to be an effective treatment for these patients. This study evaluated the efficacy and safety of HIPEC in patients with gastric cancer diagnosed from laboratory tests.MethodsThe clinical and pathological data of 63 patients with gastric cancer who underwent HIPEC in 2017–2021 were prospectively recorded. Fifty-five patients underwent cytoreductive surgery + HIPEC, and eight patients received HIPEC alone. The factors associated with HIPEC safety and efficacy were analyzed. The primary endpoint was overall survival.ResultsThe average patient age was 54.84 years and 68.3% of patients were male. Moreover, 79.4% of patients had a peritoneal carcinoma index (PCI) score of ≤ 7 and 61.9% had a completeness of cytoreduction score of 0. Because of peritoneal metastasis, 29 patients (46.03%) were classified as stage IV. Laboratory tests showed no differences in pre-HIPEC blood test results compared to post-HIPEC results after removing the effects of surgery. HIPEC treatment did not cause obvious liver or kidney damage. Serum calcium levels decreased significantly after HIPEC (P = 0.0018). The Karnofsky performance status (KPS) score correlated with the patient’s physical function and improved after HIPEC (P = 0.0045). In coagulation tests, FDP (P < 0.0001) and D-dimer (P < 0.0001) levels increased significantly and CA242 (P = 0.0159), CA724 (P < 0.0001), and CEA (P < 0.0014) levels decreased significantly after HIPEC. Completeness of cytoreduction score was an independent prognostic factor. HIPEC did not show a survival benefit in patients with gastric cancer (P = 0.5505).ConclusionHIPEC is a safe treatment for patients with gastric cancer with peritoneal metastasis based on the laboratory tests. However, the efficacy of this treatment on gastric-derived peritoneal metastases requires further confirmation.

420P The role of HIPEC in the management of gastrointestinal and biliary tract malignancies: Systematic review and meta-analysis of randomized data

The introduction of hyperthermic intraperitoneal chemotherapy (HIPEC) was hoped to transform the management of peritoneal metastases, paving the way for pioneering research. Although, a plethora of published studies on the technique exist, conclusive results stemming from randomized data remain elusive. The aim of this study is to assess the cumulative comprehensive available evidence for the use vs non-use of HIPEC treatment in gastrointestinal and biliary tract (GI) malignancies and set the current standpoint of GI HIPEC research both for prevention (adjuvant) and treatment (metastatic) of peritoneal metastases.

Current status of surgical treatment of peritoneal metastases from colorectal cancer

Cytoreductive surgery, often in combination with hyperthermic intraperitoneal chemotherapy (HIPEC), has been instrumental in improving the survival of patients with peritoneal metastases from colorectal cancer. Recent studies have highlighted the benefits of complete cytoreduction, while the role of the HIPEC treatment remains unclear. An oxaliplatin-based HIPEC over 30 min could not achieve any clear benefits in studies on colorectal cancer, neither in the therapeutic nor in the prophylactic setting, but caused relevant side effects and increased the morbidity. The negative results of these studies with respect to oxaliplatin-based HIPEC require critical appraisal; however, they should by no means be regarded as ageneral setback for surgical treatment of peritoneal metastases and be misunderstood as ageneral failure of this treatment. While HIPEC after complete surgical cytoreduction of peritoneal metastases from colorectal cancer requires further research, cytoreductive surgery should still be regarded as ahighly effective treatment for suitable patients with limited abdominal tumor dissemination.

Abdominal tissue concentrations and penetration of carboplatin in a HIPEC procedure ‒ assessment in a novel porcine model.

ObjectivesPeritoneal dissemination from intraabdominal cancers is associated with poor prognosis and rapid disease progression. Hyperthermic intraperitoneal chemotherapy (HIPEC) is an antineoplastic treatment, which has improved survival and recurrence-free survival, but little is known about the acquired chemotherapy concentrations in local tissues. The aim of this study was to assess concentrations of carboplatin during and after HIPEC treatment dynamically and simultaneously in various abdominal organ tissues by means of microdialysis in a novel porcine model.MethodsEight pigs underwent imitation cytoreductive surgery followed by HIPEC (90 min) using a carboplatin dosage of 800 mg/m2. Microdialysis catheters were placed for sampling of drug concentrations in various solid tissues: peritoneum, liver, bladder wall, mesentery and in different depths of one mm and four mm in the hepatoduodenal ligament and rectum. During and after HIPEC, dialysates and blood samples were collected over 8 h.ResultsNo statistically significant differences in mean AUC0-last (range: 2,657–5,176 min·µg/mL), mean Cmax (range: 10.6–26.0 µg/mL) and mean Tmax (range: 105–206 min) were found between the compartments. In plasma there was a tendency towards lower measures. No difference between compartments was found for tissue penetration. At the last samples obtained (450 min) the mean carboplatin concentrations were 4.9–9.9 µg/mL across the investigated solid tissues.ConclusionsEqual carboplatin distribution in abdominal organ tissues, detectable concentrations for at least 6 h after HIPEC completion, and a carboplatin penetration depth of minimum four mm were found. The present study proposes a new HIPEC porcine model for future research.

Tumor Mutational Burden Associated With Response to Hyperthermic Intraperitoneal Chemotherapy.

BackgroundGastric cancer (GC) is one of the most common cancer types, especially in Asian countries. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to improve the progression-free survival among gastric cancer patients with peritoneal metastases; however, not all patients demonstrate response to HIPEC.MethodsBiomarkers are needed to select patients for effective treatment of HIPEC. Here, we performed whole-exome sequencing on tumor samples from 18 gastric cancer patients who received HIPEC treatment and assessed the association between genomic mutation features and progression-free survival. Exome sequencing was further conducted on tumor samples from additional 15 gastric cancer patients as a replication study.ResultsThe tumor mutational burden (TMB) was significantly higher in the group of patients with a better response to HIPEC treatment than that of the others. Kaplan–Meier survival curve showed that patients with high TMB had a significantly longer survival time than that in patients with low TMB. This discovery was validated in the replication cohort. Genes bearing mutations recurrently and selectively in patients with better response to HIPEC were found in the two cohorts.ConclusionWe found that higher TMB is significantly associated with better response to HIPEC. Our results provide useful hints for prognostic stratification of HIPEC treatment.

The Correlation Between Intra-Abdominal Pressure and Tolerance to Postoperative Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei.

ObjectiveTo evaluate the correlation between pain intensity and comfort level in patients with pseudomyxoma peritoneum (PMP) before and after hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsFrom June 2018 to June 2019, patients who underwent HIPEC for PMP after surgical treatment in our institute were selected. The intra-abdominal pressure (IAP) and pain intensity (PI) before and after HIPEC were recorded, and the correlation between them was analyzed.ResultsSeventy-four patients received HIPEC 253 times. IAP and PI were significantly higher after perfusion than before perfusion (P < 0.05). When IAP < 12 cmH2O, the change of PI was not correlated to the increase of IAP, and the patient tolerated the treatment. However, when IAP > 12 cmH2O, the increase of PI was significantly associated with IAP and cause significant discomfort during the treatment.ConclusionIAP may be a monitoring index for the comfort of PMP patients during the postoperative HIPEC treatment.

Elemene-containing hyperthermic intraperitoneal chemotherapy combined with chemotherapy for elderly patients with peritoneal metastatic advanced gastric cancer.

BACKGROUNDAlmost all elderly patients with peritoneal metastatic gastric cancer (PGC) are unlikely to tolerate cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and adjuvant chemotherapy. However, determining how to optimize the treatment strategy for such patients has always been a clinical problem. Both HIPEC and palliative adjuvant chemotherapy can benefit patients with PGC. Therefore, optimizing HIPEC and chemotherapy regimens has potential clinical value in reducing side effects, and improving treatment tolerance and clinical effectiveness.AIMTo explore the effect of HIPEC containing elemene, which is an anti-cancer component extracted in traditional Chinese herbal medicine, combined with reduced capecitabine and oxaliplatin (CapeOx) chemotherapy regimens, in elderly patients with PGC.METHODSIn the present study, 39 of 52 elderly PGC patients were included and assigned to different HIPEC treatment groups [lobaplatin group (group L) and mixed group (group M)] for analysis. Lobaplatin was used for all three HIPECs in group L. In group M, lobaplatin was used in the middle of the three HIPECs, and elemene was used for the first and third HIPEC. After HIPEC, patients received CapeOx chemotherapy. The incidence of complications (abdominal infection, lung infection, and urinary tract infection), myelosuppression, immune function (CD4/CD8 ratio), average length of hospital stay, and prognosis were compared between these two groups.RESULTSThere was no significant difference in the incidence of complications between the two groups during hospitalization (P > 0.05). Compared to patients in group M, patients in group L exhibited severe myelosuppression (P = 0.027) and increased length of hospital stay (P = 0.045). However, no overall survival benefit was observed in group M. Furthermore, the immune function of patients in group M was less affected (P < 0.001), when compared to that of patients in group L. The multivariate analysis suggested that the cycles of chemotherapy after perfusion significantly affected the prognosis of patients in both groups.CONCLUSIONCompared to the lobaplatin-based HIPEC regimen, the administration of elemene reduced the myelosuppression incidence in elderly PGC patients. The present study sheds light on the implementation of this therapeutic strategy for this set of patients.

Safety evaluation of hyperthermic intraperitoneal chemotherapy in patients with local advanced gastric cancer after radical resection for prevention of peritoneal metastasis

Objective: Patients with advanced gastric cancer have a poor prognosis and a possibility of peritoneal metastasis even if receiving gastrectomy. Hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively kill free cancer cells or small lesions in the abdominal cavity. At present, preventive HIPEC still lacks safety evaluation in patients with locally advanced gastric cancer. This study aims to explore the safety of radical resection combined with HIPEC in patients with locally advanced gastric cancer. Methods: A descriptive case series study was carried out. Clinicopathological data of 130 patients with locally advanced gastric cancer who underwent radical resection + HIPEC at the Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2020 to February 2021 were retrospectively analyzed. Inclusion criteria: (1) locally advanced gastric adenocarcinoma confirmed by postoperative pathology; (2) no distant metastasis was found before surgery; (3) radical resection; (4) at least one HIPEC treatment was performed. Exclusion criteria: (1) incomplete clinicopathological data; (2) tumor metastasis was found during operation; (3) concomitant with other tumors. HIPEC method: all the patients received the first HIPEC immediately after D2 radical resection, and returned to the ward after waking up from anesthesia; the second and the third HIPEC were carried out according to the patient's postoperative recovery and tolerance; interval between two HIPEC treatments was 48 h. Observation indicators: (1) basic information, including gender, age, body mass index, etc.; (2) treatment status; (3) perioperative adverse events: based on the standard of common adverse events published by the US Department of Health and Public Health (CTCAE 5.0), the adverse events of grade 2 and above during the treatment period were recorded, including hypoalbuminemia, bone marrow cell reduction, wound complications, abdominal infection, lung infection, gastroparesis, anemia, postoperative bleeding, anastomotic leakage, intestinal obstruction, pleural effusion, abdominal distension, impaired liver function, and finally a senior professional title chief physician reviewed the above adverse events and made a safety evaluation of the patient; (4) association between times of HIPEC treatment and adverse events in perioperative period; (5) analysis of risk factors for adverse events in perioperative period. Results: Among the 130 patients, 79 were males and 51 were females with a median age of 59 (54, 66) years and an average body mass index of (23.9±7.4) kg/m(2). The tumor size was (5.4±3.0) cm and 100 patients (76.9%) had nerve invasion. All the 130 patients received radical resection + HIPEC and 125 (96.2%) patients underwent laparoscopic surgery. The mean operative time was (345.6±52.3) min and intraoperative blood loss was (82.0±36.5) ml. One HIPEC treatment was performed in 54 patients (41.5%), 2 HIPEC treatments were in 57 (43.8%), and 3 HIPEC treatments were in 19 (14.6%). The average postoperative hospital stay was (13.1±7.5) d. A total of 57 patients (43.8%) had 71 cases of postoperative complications of different degrees. Among them, the incidence of hypoalbuminemia was 22.3% (29/130), and the grade 2 and above anemia was 15.4% (20/130), lung infection was 3.8% (5/130), bone marrow cell suppression was 3.7% (4/130), abdominal cavity infection was 2.3% (3/130), and liver damage was 2.3% (3/130), wound complications was 1.5% (2/130), abdominal distension was 1.5% (2/130), anastomotic leakage was 0.8% (1/130), gastroparesis was 0.8% (1/130) and intestinal obstruction was 0.8% (1/130), etc. These adverse events were all improved by conservative treatments. There were no statistically significant differences in the incidence of adverse events during the perioperative period among patients undergoing 1, 2, and 3 times of HIPEC treatments (all P>0.05). Univariate and multivariate logistic analyses showed that age > 60 years (OR: 2.346, 95%CI: 1.069-5.150, P=0.034) and neurological invasion (OR: 2.992, 95%CI: 1.050-8.523, P=0.040) were independent risk factors for adverse events in locally advanced gastric cancer patients undergoing radical resection+HIPEC (both P<0.05). Conclusions: Radical surgery + HIPEC does not significantly increase the incidence of perioperative complications in patients with advanced gastric cancer. The age >60 years and nerve invasion are independent risk factors for adverse events in these patients.

Acute renal disease in patients with ovarian peritoneal carcinomatosis treated with cytoreduction and HIPEC: the influence of surgery and the cytostatic agent used

The main objective of this study was to evaluate the differences between cisplatin and paclitaxel in the development of postoperative renal toxicity, using as a reference the RIFLE (Risk, Injury, Insufficiency, Loss, and End-stage renal function) and AKIN (Acute Kidney Injury Network) criteria in patients with primary or recurrent ovarian cancer with peritoneal dissemination treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). One hundred fifty-two patients who were treated between December 2007 and June 2017 were analyzed. Patients who received previous platinum-based chemotherapy had higher baseline creatinine levels than those who had not (p = 0.05). A total of 11 (7.2%) and 4 (2.6%) patients developed an acute renal dysfunction (ARD) during the postoperative period of cytoreduction and HIPEC according to the RIFLE and AKI criteria respectively. RIFLE detects a higher rate of ARD due to different parameters such as GFR (7.2% versus 2.6%, p = 0.016). Performing ostomy (p = 0.007; OR: 39.320; 95% CI = 2.74-56.13) and using of cisplatin during HIPEC treatment (p = 0.017; OR = 13.619; 95% IC = 1.600-25.95) were factors independently related to a higher rate of ARD. ARD has a multifactorial origin. Cisplatin was associated with the development of a higher rate of ARD than paclitaxel. Diagnosis of ARD did not correlate with worse survival figures.