Predictive factors of non-completion of cytoreductive surgery in colorectal peritoneal metastasis.

INTRODUCTION: Cytoreductive surgery (CRS) ± hyperthermic intraperitoneal chemotherapy (HIPEC) is the only potentially curative treatment that can improve the survival prognosis for patients with peritoneal metastasis (PM) of colorectal origin. The main independent prognostic factors are extent of disease, as measured by the Peritoneal Cancer Index (PCI), and completion of CRS (CC-0 or R1). Despite thorough preoperative work-up for selection of surgical candidates, 20%-25 % of CRS procedures are stopped after exploration during laparotomy. These patients undergo "open-and-close" procedures associated with a risk of complications and without any benefit. The aim of this study was to identify preoperative predictors of non-resectability and/or non-completion of CRS in patients with colorectal PMs who were candidates for surgery. MATERIALS AND METHODS: Retrospective, monocentric study including patients admitted for CRS ± HIPEC at the Jules Bordet Institute between January 01, 2010 and December 31, 2021. The preoperative epidemiological, pathological, clinical, radiological, and biological features of patients with unresectable disease were compared with those of patients treated with CRS. RESULTS: One hundred nineteen patients were included, 60 men and 59 women (median age 61 years). Twenty-one CRS procedures (17.65 %) were stopped during exploratory laparotomy. Statistically significant factors associated with non-completion were age (p = 0.0183), PCI (p = 0.0001), presence of sub/occlusive episode(s) prior to CRS (p = 0.0012), and multifocal-diffuse uptakes on PET-scan (p = 0.0017). CONCLUSION: Almost 18 % of patients had an "open-and-close" procedure. PCI was the major determinant of non-completion of CRS. Other predictive factors of unresectability of colorectal PM were age, the presence of sub/occlusive episodes, and PET/CT with multiple peritoneal uptakes.

Prognostic Impact of Mesenteric Lymph Node Status on Digestive Resection Specimens During Cytoreductive Surgery for Ovarian Peritoneal Metastases.

BACKGROUND: The most common mode of ovarian cancer (OC) spread is intraperitoneal dissemination, with the peritoneum as the primary site of metastasis. Cytoreductive surgery (CRS) with chemotherapy is the primary treatment. When necessary, a digestive resection can be performed, but the role of mesenteric lymph nodes (MLNs) in advanced OC remains unclear, and its significance in treatment and follow-up evaluation remains to be determined. This study aimed to evaluate the prevalence of MLN involvement in patients who underwent digestive resection for OC peritoneal metastases (PM) and to investigate its potential prognostic value. METHODS: This retrospective, descriptive study included patients who underwent CRS with curative intent for OC with PM between 1 January 2007 and 31 December 2020. The study assessed MLN status and other clinicopathologic features to determine their prognostic value in relation to overall survival (OS) and progression-free survival (PFS). RESULTS: The study enrolled 159 women with advanced OC, 77 (48.4%) of whom had a digestive resection. For 61.1% of the patients who underwent digestive resection, MLNs were examined and found to be positive in 56.8%. No statistically significant associations were found between MLN status and OS (p = 0.497) or PFS ((p = 0.659). CONCLUSIONS: In anatomopathologic studies, MLNs are not systematically investigated but are frequently involved. In the current study, no statistically significant associations were found between MLN status and OS or PFS. Further prospective studies with a systematic and standardized approach should be performed to confirm these findings.

Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery.

BACKGROUND: Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any "peritoneal scar-like tissues" (PST) during CRS, hasn't been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC. METHODS: This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients' variables, were studied. RESULTS: In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS. CONCLUSION: Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts.

Deep epigastric lymph nodes implication in patients' recurrence pattern after cytoreductive surgery in ovarian peritoneal metastases.

INTRODUCTION: Although complete cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) offers a good prognosis in patients with peritoneal metastasis of ovarian cancer (PMOC), recurrences are quite common. These recurrences can be intra-abdominal or systemic in nature. Our objective was to study and illustrate the global recurrence pattern in patients operated for PMOC, shedding light on a previously overlooked lymphatic basin at the level of the epigastric artery, the deep epigastric lymph nodes (DELN) basin. PATIENTS AND METHODS: This was a retrospective study including patients with PMOC who underwent surgery with curative-intent, from 2012 until 2018, at our cancer center, and who presented with any type of disease recurrence on follow-up. CT-scans, MRIs and PET-scans were reviewed in order to determine solid organs and lymph nodes (LN) recurrences. RESULTS: During the study period, 208 patients underwent CRS ± HIPEC, 115 (55.3%) presented with organ or lymphatic recurrence over a median follow-up of 81 months. Sixty percent of these patients had radiologically enlarged LN involvement. The pelvis/pelvic peritoneum was the most common intra-abdominal organ recurrence site (47%), while the retroperitoneal LN was the most common lymphatic recurrence site (73.9%). Previously overlooked DELN were found in 12 patients, with 17.4% implication in lymphatic basin recurrence patterns. CONCLUSION: Our study revealed the potential role of the DELN basin, previously overlooked in the systemic dissemination process of PMOC. This study sheds light on a previously unrecognized lymphatic pathway, as an intermediate checkpoint or relay, between the peritoneum, an intra-abdominal organ, and the extra-abdominal compartment.

Postoperative C-reactive protein kinetics predict postoperative complications in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis.

BACKGROUND: Relatively high morbidity rates are reported after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, early predictors of complications after CRS plus HIPEC have not been identified. The aim of this study was to evaluate the predictive role of early postoperative serum C-reactive protein (CRP) level (Day 2-4) for the detection of post-operative complications. PATIENTS AND METHODS: We performed a retrospective study including 94 patients treated with complete CRS (R1) and HIPEC for PC from various primary origins (2011-2016). Post-operative complications were recorded. The values for postoperative inflammatory markers (white blood cells [WBC] and platelet counts, CRP) were compared between the different groups. RESULTS: CRP on post-operative days 2-4 was significantly higher in patients with than without complications (124 mg/L vs 46 mg/L; p < 0.0001) and higher in those with more major complications (162 mg/L vs 80 mg/L; p < 0.0012). WBC and platelet counts showed no difference within 5 days postoperatively. CONCLUSION: CRP levels, and kinetics mainly, between post-operative day 2 and 4, are decisive predictive markers of early and late post-operative complications after CRS plus HIPEC. The presence of post-operative complications should be suspected in patients with a high CRP mean, and a plateau level (days 2-4).

Fluorescence Imaging After Indocyanine Green Injection for Detection of Peritoneal Metastases in Patients Undergoing Cytoreductive Surgery for Peritoneal Carcinomatosis From Colorectal Cancer: A Pilot Study.

OBJECTIVE: The aim of this study was to evaluate the role of fluorescence imaging (FI) using an intraoperative injection of free indocyanine green (ICG) in the detection of peritoneal metastases (PM) due to colorectal cancer (CRC). BACKGROUND: A large proportion of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy will have local recurrence. This is, in part, related to the presence of small undetected nodules in the peritoneal cavity. Near-infrared FI-guided surgery has provided new opportunities for detection of nonvisible lesions during cancer surgery. METHODS: Patients with PM from CRC admitted for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were selected for participation in this study (NCT02032485). Free ICG, at 0.25 mg/kg of patient weight, was intravenous (IV)-injected intraoperatively. Tumor-to-background ratio was calculated for all suspect resected PM. RESULTS: Sixty-three of 78 peritoneal resected nodules in 14 patients were evaluated for fluorescence, among them, 53 were malignant (84%) and 10 benign (16%). Twenty-six were hypofluorescent, 16 moderately hyperfluorescent, and 21 hyperfluorescent. Amongst the 42 nodules of the 9 patients with nonmucinous adenocarcinoma, the mean tumor-to-background ratio was 1.92 (SD 0.67) in malignant and 1.02 (SD 0.06) in benign nodules (P = 0.0099). In 4 of 14 patients (29%), the surgery was modified by intraoperative ICG-FI, which detected additional PM not found using visualization and palpation. CONCLUSIONS: This pilot study demonstrates that non-mucinous PM of CRC can be visualized intraoperatively using ICG-FI. Furthermore, ICG-FI findings resulted in modification of the planned surgery in 29% of patients.

Interval Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in First-Line Treatment for Advanced Ovarian Carcinoma: A Feasibility Study.

OBJECTIVES: We conducted a phase 2 trial to assess the feasibility of interval cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin in patients with stage III and IV pleural ovarian carcinoma in first-line treatment with no macroscopic residual disease after surgery. METHODS: Patients could be treated either with primary CS with HIPEC followed by 6 conventional cycles of chemotherapy or with 3 or 4 cycles of neoadjuvant chemotherapy before CS with HIPEC and 3 postoperative chemotherapy cycles. Hyperthermic intraperitoneal chemotherapy was performed with cisplatin (50 mg/m) for 60 minutes, only in case of complete cytoreduction. RESULTS: Nineteen patients were included in the study, and they all underwent neoadjuvant chemotherapy before CS. Sixteen patients underwent complete CS with HIPEC. There was no mortality, and morbidity of CS with HIPEC was acceptable. The HIPEC procedure did not prevent the administration of the standard first-line treatment. In the 16 patients who underwent CS with HIPEC, the outcomes were very good. CONCLUSION: Our study shows an acceptable toxicity of adding HIPEC to the standard first-line treatment in patients with stage III ovarian carcinoma treated with interval CS. Further studies are needed to confirm the role of HIPEC in the treatment of ovarian carcinoma.