Neoadjuvant chemotherapy does not improve survival for patients with high volume colorectal peritoneal metastases undergoing cytoreductive surgery.

BACKGROUND: Colorectal peritoneal metastases (CRPM) affects 15% of patients at initial colorectal cancer diagnosis. Neoadjuvant chemotherapy (NAC) prior to cytoreductive surgery (CRS) has been demonstrated to be a safe and feasible option, however there is limited data describing its efficacy in advanced peritoneal disease. This study evaluated the effect of NAC on survival in patients with high volume CRPM undergoing CRS with or without HIPEC. METHODS: A retrospective review of all patients who underwent CRS with or without HIPEC for CRPM from 2004 to 2019 at our institution was performed. The cohort was divided based on peritoneal carcinomatosis index (PCI) at surgery: Low Volume (PCI ≤ 16) and High Volume (PCI > 16). RESULTS: A total of 326 patients underwent CRS with HIPEC for CRPM. There were 39 patients (12%) with High Volume disease, and 15 of these (38%) received NAC. Patients with High Volume disease had significantly longer operating time, lower likelihood of complete macroscopic cytoreduction (CC-0 score), longer intensive care unit length of stay and longer hospital stay compared to Low Volume disease. In High Volume disease, the NAC group had a significantly shorter median survival of 14.4 months compared to 23.8 months in the non-NAC group (p = 0.046). CONCLUSION: Patients with High Volume CRPM achieved good median survival following CRS with HIPEC, which challenges the current PCI threshold for offering CRS. The use of NAC in this cohort did not increase perioperative morbidity but was associated with significantly shorter median survival compared to upfront surgery.

Repeat cytoreductive surgery with HIPEC for colorectal peritoneal metastases: a systematic review.

BACKGROUND: Colorectal peritoneal metastases (CRPM) are present in 10-20% of patients at the time of their initial cancer diagnosis, and affects over 20% of those who develop colorectal cancer recurrence. Cytoreductive surgery (CRS) with HIPEC is firmly established as the optimal surgical treatment, but there is very little known about the benefit of repeat or iterative CRS. The aim of this review is to provide a systematic evaluation of the perioperative complications, survival outcomes and quality of life in patients undergoing repeat CRS with HIPEC for CRPM. METHODS: A systematic review of PubMed, Ovid MEDLINE, EMBASE, Scopus and Cochrane databases was performed to identify all studies that reported outcomes for repeat CRS with or without HIPEC for CRPM. RESULTS: Four hundred and ninety-three manuscripts were screened, and 15 retrospective studies were suitable for inclusion. Sample sizes ranged from 2 to 30 participants and comprised a total of 229 patients. HIPEC was used in all studies, but exact rates were not consistently stated. Perioperative morbidity was reported in four studies, between 16.7% and 37.5%. Nine studies reported mortality rate which was consistently 0%. The median overall survival after repeat CRS ranged from 20 to 62.6 months. No studies provided quality of life metrics. CONCLUSION: Repeat CRS for CRPM has perioperative morbidity and mortality rates comparable to initial CRS, and offers a potential survival benefit in selected patients. There is however limited high-quality data in the literature.

Complexity of surgery and treatment burden in patients with peritoneal malignancy is not determined by addition of hyperthermic intraperitoneal chemotherapy.

BACKGROUND: This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves. RESULTS: 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed. CONCLUSIONS: The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding.

Comparing Survival Outcomes and Impact of EPIC in Patients Undergoing CRS/HIPEC for Mucinous Appendiceal Neoplasm.

BACKGROUND/AIM: This study sought to investigate the difference in survival outcomes in patients with complete cytoreduction (CC)-0 or CC-1 mucinous appendiceal cancer undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). It also investigated what effect early postoperative intraperitoneal chemotherapy (EPIC) may have on survival based on CC score and histology. PATIENTS AND METHODS: This was a retrospective single centre study of patients that underwent CRS/HIPEC +/- EPIC for mucinous appendiceal neoplasms from June 2003 to February 2022. RESULTS: A total of 545 patients were identified. Although there was a survival difference between CC-0 and CC-1 on univariate analyses, this was not statistically significant on multivariate analysis. Histology, peritoneal cancer index, and EPIC status were demonstrated to be independent factors that affected overall survival (OS) on multivariate analysis. Patients with CC-1 that received EPIC had significantly improved OS (mean OS 14 years) when compared to patients that did not receive EPIC (mean OS 6 years). In CC-1, OS was significantly improved in patients that received EPIC in both low-grade (p<0.001) and high-grade (p=0.012) disease. OS for patients that received EPIC at 1, 5, and 10 years was 95%, 80%, and 59%, respectively. OS for patients that did not receive EPIC at 1, 5, and 10 years was 84%, 49%, and 30%, respectively. CONCLUSION: There was no difference in OS between CC-0 and CC-1. The implementation of EPIC in patients with CC-1 significantly improved OS in both low-grade and high-grade disease and thus we recommend its addition in CC-1 disease to achieve optimal survival outcome.

Cytoreductive Surgery and HIPEC for Malignant Peritoneal Mesothelioma: Outcomes and Survival From an Australian Centre.

BACKGROUND/AIM: The aim of the study was to determine outcomes and overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for malignant peritoneal mesothelioma (MPM). PATIENTS AND METHODS: This was a retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for MPM from April 1999 to December 2021. RESULTS: A total of 81 patients were identified with MPM. Median OS was 53 months with a 1-, 3- and 5-year OS of 76%, 55% and 49% respectively. Multivariate analysis identified lymph node status, PCI and CC score as statistically significant prognostic factors that impact survival. Median OS for PCI 0-20 was 103 months vs. 33 months for PCI 21-39 (p=0.005). Median OS for CC0, CC1 and CC2 were 104, 30 and 2.7 months respectively (p<0.001). Hazard ratio for node-positive disease over node-negative was 2.14 (95% CI=1.07-4.31, p<0.033). Grade III/IV complication rate was 43.2% and mortality 4.9%. CONCLUSION: CRS/HIPEC remains the gold standard for treating patients with MPM with excellent patient OS. Lymph node status, PCI and CC score were independent prognostic factors that affect OS.

Managing Recurrent Pseudomyxoma Peritonei in 430 Patients After Complete Cytoreduction and HIPEC: A Dilemma for Patients and Surgeons.

BACKGROUND: Epithelial appendiceal neoplasms are uncommon peritoneal malignancies causing a spectrum of disease including pseudomyxoma peritonei (PMP). The optimal management is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite complete CRS (CCRS), recurrence develops in almost 45% of patients. No consensus exists for the optimal treatment of recurrent disease, with treatment strategies including repeat CRS, watch-and-wait, and palliative chemotherapy. This report aims to describe evolving management strategies for a large cohort with recurrence after CCRS. METHODS: This retrospective study analyzed a prospective database of patients with recurrence after CCRS for appendiceal neoplasms from 1994 to 2017 who had long-term follow-up evaluation with tumor markers and computed tomography (CT). RESULTS: Overall, 430 (37.6%) of 1145 PMP patients experienced recurrence at a median of 19 months. Of these 430 patients 145 (33.7%) underwent repeat CRS, 119 (27.7%) had a watch-and-wait approach, and 119 (27.7%) had palliative chemotherapy. The patients with recurrence had a median overall survival (OS) of 39 months, a 3-year survival of 74.6%, a 5-year survival of 57.4%, and a 10-year survival of 36.5%. In the multivariate analysis, the patients who had recurrence within 1 year after primary CRS (hazard ratio [HR], 3.55), symptoms at recurrence (HR, 3.08), a high grade of disease or adenocarcinoma pathology (HR, 2.94), signet ring cells (HR, 1.91), extraperitoneal metastatic disease (HR, 1.71), or male gender (HR, 1.61) had worse OS. The OS was longer for the patients who had repeat CRS (HR, 0.41). The patients who underwent repeat CCRS had a 3-year OS of 87.5%, a 5-year OS of 78.1%, and a 10-year OS of 67.9%. CONCLUSIONS: Dilemmas persist around the optimal management of patients with recurrence after CRS and HIPEC for appendiceal tumors. Selected patients benefit from repeat CRS, particularly those with favorable tumor biology and focal disease.

Patients undergoing cytoreductive surgery for peritoneal malignancy of appendiceal origin should be consented for umbilical excision as 30% have umbilical infiltration.

AIM: Cytoreductive surgery (CRS) for peritoneal malignancy has traditionally included umbilical excision with no published evidence on the incidence of umbilical involvement. The primary aim of this work was to determine the incidence of umbilical involvement in patients undergoing CRS for peritoneal malignancy of appendiceal origin. The secondary aim was to investigate the relationship of umbilical involvement with prior surgery affecting the umbilicus, such as diagnostic laparoscopy and midline laparotomy. METHOD: This study is from a national referral centre in the United Kingdom for appendiceal tumours and peritoneal malignancy. It is a retrospective analysis from a dedicated prospective database. We evaluated the most recent 200 consecutive patients who underwent CRS for peritoneal malignancy of appendiceal origin where all pathology specimens were reported by a recognized expert pathologist in appendiceal tumours and peritoneal malignancy. RESULTS: From June 2016 to September 2019, 200 consecutive patients had CRS and 178 had umbilical excision. Of these 54/178 (30.3%) had disease involving the umbilicus. The pathological findings in the 178 patients were low-grade mucinous carcinoma peritonei in 90/178 (50.6%), high-grade mucinous carcinoma peritonei in 31/178 (17.4%), metastatic appendiceal adenocarcinoma in 29/178 (16.4%) and diffuse acellular mucin in 28/178 (15.7%). Umbilical involvement was found in 25/90 (27.8%) with low-grade, 11/31 (35.5%) with high-grade, 8/29 (27.6%) with adenocarcinoma and 10/28 (35.7%) of patients with acellular mucin. In the 54 patients with umbilical disease, 30/54 (55.6%) had previous diagnostic surgery affecting the umbilicus. In the 124 patients without umbilical disease, 76/124 (61.2%) had prior surgery involving the umbilicus. The difference between the groups was not significant (p = 0.24). CONCLUSION: In patients with peritoneal malignancy of appendiceal origin, approximately 30% have umbilical involvement, irrespective of the primary appendiceal pathology. Umbilical involvement was not associated with prior surgery involving the umbilicus. This is the first report to document the incidence of umbilical pathology and supports consideration of routine umbilical excision in CRS for peritoneal malignancy.

Physicochemical Characterization, Antioxidant Activity, and Phenolic Compounds of Hawthorn (Crataegus spp.) Fruits Species for Potential Use in Food Applications.

Hawthorn belongs to the Crataegus genus of the Rosaceae family and is an important medicinal plant. Due to its beneficial effects on the cardiovascular system and its antioxidant and antimicrobial activity hawthorn has recently become quite a popular herbal medicine in phytotherapy and food applications. In this study, physicochemical characterization (color parameters, pH, titratable acidity, total soluble solids, soluble carbohydrate, total carotenoid, total phenols, and flavonoid contents), antioxidant activity (by ferric-reducing antioxidant power, FRAP assay), and quantification of some individual phenolic compounds of fruits of 15 samples of different hawthorn species (Crataegus spp.) collected from different regions of Iran were investigated. According to findings, the total phenols, total flavonoid content, and antioxidant activity were in the range of 21.19-69.12 mg gallic acid equivalent (GAE)/g dry weight (dw), 2.44-6.08 mg quercetin equivalent (QUE)/g dw and 0.32-1.84 mmol Fe++/g dw, respectively. Hyperoside (0.87-2.94 mg/g dw), chlorogenic acid (0.06-1.16 mg/g dw), and isoquercetin (0.24-1.59 mg/g dw) were found to be the most abundant phenolic compounds in the extracts of hawthorn fruits. The considerable variations in the antioxidant activity and phenolic compounds of hawthorn species were demonstrated by our results. Hence, the evaluation of hawthorn genetic resources could supply precious data for screening genotypes with high bioactive contents for producing natural antioxidants and other phytochemical compounds valuable for food and pharma industries.