Doxorubicin as Risk Factor for Fascial Dehiscence After CRS-HIPEC for Peritoneal Metastases.

BACKGROUND/AIM: Among postoperative complications, fascial dehiscence (FD) is registered in up to 10% of patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aimed to evaluate the risk factors related to FD after CRS-HIPEC. PATIENTS AND METHODS: A retrospective analysis of a prospectively maintained database of consecutive patients who underwent CRS-HIPEC between 2015 and 2023 was performed. For each patient, risk factors for postoperative fascial dehiscence were identified using multivariate analysis. RESULTS: During the study period (2018-2023), 217 patients were treated with CRS-HIPEC. The incidence of FD was observed in seven cases (3.2%), which were reoperated with direct fascial closure. In three cases, FD was associated with other grade III-IV complications. Body mass index, (BMI; p=0.024), doxorubicin-based HIPEC (p=0.005), and open technique (p=0.004) were identified as risk factors for FD in univariate analysis. Systemic chemotherapy, prior surgical score, and peritoneal cancer index (PCI) were not associated with an increased risk of FD. In multivariable regression analysis, doxorubicin-based HIPEC and open technique were confirmed as risk factors for FD. CONCLUSION: Although FD is a relatively rare event after CRS-HIPEC, open technique and doxorubicin-based HIPEC were significant predictors of this complication. Specific fascial closure techniques and proper wound care should be considered in high-risk patients.

Is Systemic Chemotherapy Useful in Patients Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Colorectal Peritoneal Metastases? A Propensity-Score Analysis.

PURPOSE: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. METHODS: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. RESULTS: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). CONCLUSIONS: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.

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

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

HIPEC as a risk factor for postoperative coagulopathy after cytoreductive surgery for peritoneal metastases.

AIM OF THE STUDY: Postoperative coagulopathy is a poorly investigated condition after Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). This study aims to evaluate the occurrence and risk factors of coagulative disorders after surgery for peritoneal metastases. PATIENTS AND METHODS: The records were extracted from a prospectively maintained database of consecutive patients who underwent CRS between January 2018 and September 2020. The study was approved by the local Ethics Committee. For each patient, the coagulation profile (CP), which included international normalized ratio (INR), partial thromboplastin time (aPTT), and platelets (PLTS) before surgery, intensive care unit admission,1st, 3rd, 5th postoperative day (POD) and the day before discharge was collected. Risk factors for postoperative coagulopathy were identified at multivariate analysis. RESULTS: During the study period, 125 patients were included in the study. Among these, 48 (38.4%) underwent CRS only, and 77 (61.6%) CRS followed by HIPEC. Twenty-one patients (16.8%) developed severe coagulopathy, 5 (10.4%) after CRS and 16 (20.8%) after CRS-HIPEC. At multivariate analysis, HIPEC and blood loss ≥ 500 ml represented independent risk factors for severe alteration of INR > 1.5 (p = 0.05, OR 1.2) and PLTS < 75 109/L (p = 0.03, OR 1.3), respectively. CONCLUSION: HIPEC is an independent risk factor for postoperative coagulopathy after CRS. Further studies are necessary to assess the usefulness of the point-of-care test in patients treated with CRS-HIPEC.

Complete pathological response of colorectal peritoneal metastases in Lynch syndrome after immunotherapy case report: is a paradigm shift in cytoreductive surgery needed?

BACKGROUND: We report the first case of a patient affected by peritoneal metastases from colon cancer, arising in the context of Lynch syndrome with pathological complete response. The patient was treated with immunotherapy and cytoreductive surgery. This paper discusses the implications of these novel therapies for the management of PM. CASE PRESENTATION: A 50-year-old man affected by Lynch syndrome was referred to our institution for metachronous peritoneal recurrence of ascending colon adenocarcinoma. As a second-line treatment, he received Nivolumab therapy with stable disease. Patient underwent cytoreductive surgery with residual disease and a pathological complete response. Flow cytometry described a particular immune sub-population response. There was no evidence of disease progression after nine months. CONCLUSION: This is the first report of a Lynch patient affected by peritoneal metastases of colorectal cancer, treated with cytoreductive surgery (CRS) and resulting in a pathological complete response after immune checkpoint inhibitors treatment (ICIs). This case report may suggest that patients with peculiar immunological features could benefit from a tailored approach, since "classical" CRS paradigms may not effectively predict the clinical outcome. Further large-scale studies are needed to determine the correct operative management of such patients (tailored or "standard" CRS), defining the correct surgical timing and eventual discontinuation of ICI therapy after surgery.

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. METHODS: Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. CONCLUSION: For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.

Colic and rectal tumors with peritoneal metastases treated with cytoreductive surgery and HIPEC: One homogeneous condition or two different diseases? A systematic review and meta-analysis.

Colorectal cancer (CRC) peritoneal metastasis (PM) is one of the most important cause of cancer-related death in world. CRC PM is considered as a homogeneous disease without differentiating colonic or rectal origin. Aim of this study is to analyze survival of patients treated with cytoreductive surgery and HIPEC, according to the origin of PM. Literature search was performed to identify relevant articles. All meta-analysis were performed using mean difference and log of HR, when appropriate. The I2 statistic was used to determine the heterogeneity of included studies. Out of 349 selected records, 9 articles (1308 patients, 1153 colon PM and 155 rectal PM) have been included. OS and DFS is higher in patients affected by colon PM (OS mean difference: 24,49 months [95% CI: 14,70-34,28 months, p < 0,000001]; DFS mean difference: 7,75 months [95% CI: 1,37-14,13 months, p: 0,02]) and pooled Hazard Ratio for disease-related death in rectal PM is 1.62 [95% CI: 1,01-2,59, p: 0,05] compared to colon PM). Heterogeneity among selected studies is high in two subgroups and low in one (OS subgroup A I2: 98%, p < 0,000001; DFS subgroup I2: 91%, p < 0,000001; OS subgroup B I2: 25%, p: 0,26). Our analysis, with all the limitations related to included studies, suggests that peritoneal metastasis of rectal tumors treated with CRS and HIPEC have a worst prognosis of colon tumors PM. Larger studies are required to confirm those results and therefore we invite all Authors in considering also tumor localization when reporting data on CRC peritoneal metastasis treatment.

Iterative Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Peritoneal Metastases.

BACKGROUND: Our aim was to analyze the safety and efficacy of iterative cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (iCRS-HIPEC) in patients with peritoneal recurrence from different tumor types. PATIENTS AND METHODS: Data on indications, intraoperative findings and postoperative outcome of all patients treated with iCRS-HIPEC at our Institution were reviewed. RESULTS: Between 2010-2018, 10 iCRS-HIPEC procedures for peritoneal recurrence in eight patients were performed. The median peritoneal cancer index was 14.5 (range=2-33). Completeness of cytoreduction was CC0-1 in most cases (9/10). Three grade III-IV complications (two intestinal fistulas, one bleeding) were recorded and there was no operative mortality. After a median follow-up of 19.5 months, six patients experienced recurrence after a median of 12.5 months. CONCLUSION: iCRS-HIPEC is a safe procedure in selected patients with recurrent peritoneal surface malignancies. Selection criteria still remain questionable and need to be further evaluated in large cooperative multi-institution studies.

Novel Therapy for Pediatric Angiosarcoma With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

The management of pediatric abdominopelvic angiosarcoma remains unclear due to limited clinical experience. Herein, we presented the first 2 pediatric patients with abdominal angiosarcoma who were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant therapy. The first patient is alive with recurrent disease at 1-year follow-up and the second patient remains disease free after 1 year. CRS and HIPEC should be considered as a therapeutic option in the management of pediatric abdominal angiosarcomas. A multi-institutional international shared registry is needed to further evaluate the role of CRS and HIPEC in inducing remission of abdominopelvic angiosarcomas in the pediatric population.

Diagnostic value of contrast-enhanced CT combined with 18-FDG PET in patients selected for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

PURPOSE: Aim of the study is to assess the reliability and correlation with surgical peritoneal cancer index (PCI) of combined PET/CT and ceCT scans (PET/ceCT) performed in a session in patients with peritoneal carcinomatosis candidates for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We retrospectively analyzed data collected from 27 patients with different types of peritoneal carcinomatosis candidates to CS + HIPEC who underwent FDG PET/ceCT in a single session. Two nuclear medicine physicians and two radiologists independently and blindly evaluated PET/CT and ceCT imaging, respectively. In the case of discordance, the consensus was reached by a discussion between the specialists. Moreover, the combined images were evaluated by all the specialists in consensus. The PCIs obtained from surgical look, PET/CT, ceCT, and PET/ceCT were compared with each other. The coefficients of correlation (r) were calculated. The study was conducted after approval of local ethics committee. RESULTS: Surgical PCI was available in 21 patients. The coefficient of correlation between PCI of PET/CT and surgery was 0.528, while it resulted higher between PET/ceCT and surgery (r = 0.878), very similar to ceCT and surgery (r = 0.876). The r coefficient between surgical PCI and PET/CT was higher in patients with a non-mucinous cancer (n = 12) than the counterpart (0.601 vs. 0.303) and the addition of ceCT significantly increases the correlation (r = 0.863), which is anyway similar to ceCT alone (r = 0.856). CONCLUSIONS: PET/ceCT as single examination is more accurate than PET/CT but not than ceCT alone for the definition of PCI in a selected group of patients candidates to CS + HIPEC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal sarcomatosis: long-term outcome from a single institution experience.

AIM: We assessed the long-term local disease-free survival (LDFS) and overall survival (OS) of patients with peritoneal sarcomatosis (PS) uniformly-treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS plus HIPEC). PATIENTS AND METHODS: Retrospective data of 15 patients who underwent CS plus HIPEC for PS were extracted from a prospectively collected database. DFS and OS were calculated from the date of CS plus HIPEC to local relapse and death, respectively. RESULTS: After a median follow-up of 28 months (range=4-144 months), median LDFS was 15 months (95% Confidence Interval CI=1-40 months). Median OS was 27 (95% CI=24.7-29.3) months. Long-term OS was achieved in three patients (20%) and ranged between 93 and 144 months. Female sex was the only factor significantly correlated with a greater LDFS (p=0.018). Patients with PS of visceral origin seem at lower risk of recurrence and death but the difference did not prove significant. CONCLUSION: In our series, long-term survival was achieved in 20% of patients after CS plus HIPEC, with a benefit in female patients with PS of visceral origin. The impact of HIPEC after radical surgery for PS remains questionable and still has to be further evaluated in large cooperative multi-institutional studies.

The role of laparoscopy in peritoneal surface malignancies selected for hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was developed as locoregional treatment for primary or secondary peritoneal tumors. The role of laparoscopy over several stages of diagnosis and the treatment of the patients affected by peritoneal carcinomatosis and selected for CS + HIPEC shows some peculiarities, and their potential application in this field is not fully known. Our aim was to review and summarize the applications, the results, and the future directions of laparoscopy in the management of the patients affected by carcinomatosis and scheduled for CS + HIPEC. METHODS: Appropriate keywords were adopted to identify the relevant studies on this topic in PubMed/Medline electronic databases. RESULTS: The role of laparoscopy in diagnosis and staging of patients selected for CS + HIPEC seems to have a great but probably underestimated potential. Laparoscopic CS + HIPEC is technically feasible with an acceptable morbidity profile, especially in patients with low tumor load. In selected patients with malignant ascites, laparoscopic HIPEC achieves a good palliative effect, with a low morbidity profile. CONCLUSIONS: Laparoscopy plays a partially explored role in diagnosis and staging of patients selected for CS + HIPEC. The use of laparoscopic HIPEC with an adjuvant, curative, or palliative intent seems feasible, but further studies are required in order to explore and validate all potential indications. For all these reasons, it would be advisable to provide every HIPEC center with specific laparoscopic skills.

Cyto-reductive Surgery combined with Hyperthermic Intra-peritoneal Chemotherapy for Peritoneal Surface Malignancies: current treatment and results.

Cyto-reductive Surgery (CS) combined with Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) as loco-regional treatment of Peritoneal Surface Malignancies (PSM) has increasingly gained acceptance in clinical practice. This review summarizes the more relevant studies on this topic. Indications, pre-operative work-up, technical aspects, outcome and future directions of this combined approach in the treatment of Peritoneal Surface Malignancies are discussed here and proposed in an informative and didactic manner.