Second-look Surgery for Appendiceal High Grade and Colorectal Cancers Following Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND/AIM: Up to a third of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) of appendiceal or colorectal origin receive a stoma during primary surgery. Stoma reversal provides an opportunity for second-look surgery. PATIENTS AND METHODS: We performed a retrospective analysis of prospectively collected data of patients with colorectal cancer (CRC) or high-grade appendiceal cancer (AC) from 2006 to 2021 from our database. A total of 34 consecutive stoma closure patients with no evidence of preoperative disease recurrence (tumor markers and CT scans) were compared with 141 consecutive re-do CRS/HIPEC patients with known recurrence. RESULTS: Eleven patients (32.4%) were identified to have peritoneal recurrence at stoma closure. Time between first and second CRS was 12 months (4 to 64.2) in the stoma closure group vs. 24.6 months (5.8 to 119.8) in the re-do group, while median peritoneal cancer index (PCI) was 4 (3 to 6) vs. 8 (1 to 39), respectively (p=0.0143). CONCLUSION: Second-look laparotomy during stoma closure identified unexpected PC in 32.4% of our patients with significantly lower PCI than planned re-do operations.

Outcomes and prognostic factors of cytoreductive surgery and perioperative intraperitoneal chemotherapy in high-volume peritoneal carcinomatosis.

BACKGROUND AND OBJECTIVES: The management of patients with extensive appendiceal mucinous neoplasms and mesothelioma is controversial. Our aims were to analyze overall survival (OS), disease-free survival (DFS) and independent prognostic factors associated with high peritoneal cancer index (PCI) status in patients who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). METHODS: A prospectively-maintained database for patients with appendiceal neoplasms and mesothelioma undergoing CRS/PIC from year 1996 to 2018 was retrospectively analyzed. Patients who achieved complete cytoreduction were stratified into limited (PCI < 30) and extensive (PCI ≥ 30) disease groups. RESULTS: 260 female and 235 male patients were identified. The 5-year survival for low-grade appendiceal mucinous neoplasms (LAMN) was significantly higher in the low PCI group (96.2% vs. 63.5%, p < 0.001). There was no difference in the OS across both groups in high-grade appendiceal mucinous neoplasms (HAMN) (63 vs. 69 months; p = 0.942) and mesothelioma (72 vs. 42 months; p = 0.058). Overall mortality was 2%. Grade III/IV complications were significantly higher in extensive disease (68% vs. 36.6%, p < 0.001). On multivariate analysis, use of EPIC and blood transfusion (>8 units) were independent positive and negative prognostic factors, respectively, associated with OS. Meanwhile, use of EPIC conferred benefit in DFS while increased blood transfusion (>8 units) and elevated preoperative CA125 were predictive of a poor DFS. CONCLUSION: Long-term survivals following CRS/PIC are achievable with acceptable mortality and higher morbidity rates in extensive appendiceal mucinous neoplasms and mesothelioma. High PCI status does not preclude treatment with CRS/PIC.

Cost-effectiveness of Iterative Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Carcinomatosis.

BACKGROUND: Iterative cytoreduction (iCRS) and hyperthermic intraperitoneal chemotherapy is a treatment for recurrence of peritoneal carcinomatosis. There are considerable upfront costs for this approach for which the cost-effectiveness has not been evaluated. PATIENTS AND METHODS: We used a prospectively maintained database of patients having undergone primary and iterative cytoreduction at St. George Hospital between January 1, 2014, and December 31, 2017, which was linked with financial data. Cost effectiveness and survival outcomes were used to compare primary cytoreduction (pCRS) and iterative cytoreduction (iCRS) in addition to comparison with other treatment modalities. RESULTS: The average cost per patient in Australian dollars was $69,295 ($14,691-$696,002) and the average cost per life-year was $15,842. There was no difference in cost-effectiveness between those who had undergone pCRS and those who had undergone iCRS. The overall survival was 52.5 months (95% confidence interval=49.7-55.2 months) with no difference in survival between pCRS and iCRS groups. The median length of hospital stay was significantly longer for patients in the pCRS treatment group (25.51 days) when compared to the iCRS treatment group (21.15 days, p=0.034). CONCLUSION: iCRS is a cost-effective treatment in the management of recurrent peritoneal carcinomatosis.

Strategies for 'bloodless' surgery: the experience of cytoreductive surgery for peritoneal carcinomatosis in Jehovah's Witnesses.

BACKGROUND: Cytoreductive surgery (CRS) for the management of peritoneal carcinomatosis (PC) can involve significant blood loss which necessitates the transfusion of blood products. This poses a particular challenge in the Jehovah's Witnesses population whose beliefs do not permit the transfusion of blood products or blood-related derivatives. This report describes the experience of one institution performing CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) for PC in Jehovah's Witnesses and perioperative management strategies employed to avoid blood transfusion. METHODS: A review of literature and prospectively collated data of Jehovah's Witnesses patients who underwent extensive CRS for PC and HIPEC for PC. RESULTS: Four patients had CRS and HIPEC for PC. The median PC index score was 11 and complete cytoreduction was achieved in all cases. Primary tumours were ovarian (n = 1), colorectal (n = 2) and neuroendocrine tumour of gastrointestinal origin (n = 1). The median difference between preoperative and postoperative haemoglobin was 38 g/L (23-43 g/L). Strategies included acute normovolumaeic haemodilution and autotransfusion within a closed circuit, autotransfusion from cell salvage and provisions for possible use of a haemoglobin based oxygen carrier. Ancillary measures identified and implemented to minimize transfusion dependence included, but were not limited to, preoperative iron infusion, perioperative acute haemodilution and cell salvage, administration of tranexamic acid, prothrombinex and use of paediatric tubes for venepuncture. CONCLUSION: The review suggests CRS and HIPEC for extensive PC can be done safely in circumstances where transfusion of allogenic blood products is not permitted.

Impact of Cytoreductive Surgery and HIPEC on Intraoperative Gastrointestinal Wall Thickness and Patient Outcomes.

BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is associated with significant postoperative ileus (POI). This study examined intraoperative gastrointestinal wall thickness (GWT) and its association with patient outcomes. PATIENTS AND METHODS: A prospective study of patients undergoing CRS and HIPEC. Proximal and distal small intestine GWT, before and after HIPEC were recorded. RESULTS: Thirty-four patients (mean age=56.1 years, 61.8% female) were recruited. After HIPEC, the mean proximal (4.5 vs. 3.0 mm, p=0.03) and distal (4.3 vs. 3.4 mm, p<0.01) GWT were increased. Increased GWT was associated with prolonged operative time (10 vs. 8.5 h, p=0.03) and total length of stay (35.71 vs. 21.25 days, p=0.02). Postoperative ileus occurred in 23.5% of patients but differences between GWT groups did not reach significance (28.6% vs. 20%, p=0.56). CONCLUSION: GWT increased significantly during CRS and HIPEC and is reflective of tissue trauma and oedema. This was associated with prolonged operative time, total length of stay and post-operative ileus.

Intraoperative packed red blood cell transfusion (iPRBT) and PCI-normalised iPRBT rates (iPRBT/PCI ratio) negatively affect short- and long-term outcomes of patients undergoing cytoreductive surgery and intraperitoneal chemotherapy - An analysis of 880 patients.

BACKGROUND: Most studies on the effects of intraoperative packed red blood cell transfusions (iPRBT) on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown deleterious outcomes. It is unclear if this is a result of the transfusion itself or because iPRBTs serve as a surrogate of more advanced disease. METHODS: A retrospective analysis of 880 patients treated from 1996 to 2017. The effect of any exposure to iPRBT as well as the effect of peritoneal cancer index (PCI)-normalised iPRBT rates (ratio of iPRBT/PCI) on patients short- and long-term outcomes (recurrence-free (RFS) and overall survival (OS)) were assessed. Equally, the prognostic effect of postoperative PRBTs was analysed and adjusted for. RESULTS: Of the 880 patients included, only 26.4% had no iPRBT whereas 59.2% of patients had no postoperative PRBT. Patients with no iPRBTs had significantly lower PCIs, less high-grade complications, shorter ICU and hospital length of stay, as well as improved RFS and OS. Furthermore, high PCI-normalised iPRBTs resulted in worse perioperative and long-term outcomes, with a median OS of 41 months vs. 103 months (5-year survival rate 36.6% vs. 66.1%; p < 0.001) and median RFS of 13 months vs. 30 months (5-year RFS rate 18.3% vs. 37.6% p < 0.001) compared to those with a low iPRBT/PCI ratio. This independent effect was confirmed upon multivariable Cox regression analysis which corrected for important confounders including complexity of procedures and postoperative PRBTs (adjusted HR [aHR]2.04, 95%CI 1.36-3.04, p = 0.001 for OS; aHR 1.38, 95%CI 1.06-1.81, p = 0.017 for RFS). However, subgroup analysis (stratified by histopathologic disease entities) revealed that this independent prognostic effect was seen in high-grade mucinous appendiceal neoplasms, whereas PCI-normalised IPRBTs were not significantly prognostic in other histopathologic subgroups. CONCLUSION: iPRBTs significantly and independently impact perioperative and long-term outcomes of patients undergoing CRS/HIPEC. However, this effect mainly seems to occur in patients with high-grade mucinous neoplasms, whereas it may only be of borderline prognostic significance in other patient groups. The development of blood-sparing protocols may help improve outcomes of patients undergoing this complex oncologic procedure.

Short- and Long-Term Outcomes of Patients Requiring Gastrectomy During Cytoreductive Surgery and Intraperitoneal Chemotherapy for Lower-Gastrointestinal Malignancies: A Propensity Score-Matched Analysis.

OBJECTIVES: This study was designed to assess the short- and long-term outcomes of gastric resection in cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for lower gastrointestinal (GI) malignancies. METHODS: Patients with adenocarcinoma and appendiceal mucinous neoplasms were included. Redo and incomplete cytoreductions were excluded. A total of 756 patients were identified. Of these, 65 underwent gastric resection, 11 underwent wedge, 43 distal, and 11 subtotal and total gastrectomy. Preoperative differences were assessed for and addressed with matching. Perioperative outcomes, overall survival (OS), and risk-free survival (RFS) were assessed in two analyses: first all gastric resections were included and the second excluded wedge resections. Subgroup analysis according to diagnosis subtype was conducted. RESULTS: Demographic analysis revealed that markers of tumor aggression and poor nutrition were prevalent in the gastrectomy group. The matched analysis for gastric resections revealed higher rates of reoperation (38% vs. 22%, p = 0.028). After excluding wedge resections, increased rates of reoperation (40% vs. 22%, 0.019), grade 3/4 morbidity (76% vs. 59%, p = 0.036), and hospital stay (34 vs. 27 days, p = 0.012) were observed. For the unmatched cohort, OS (103 vs. 69 months, p = 0.501) and RFS (17 vs. 18 months, p = 0.181) for patients with CC = 0 were insignificantly different. In comparison for CC > 0, OS (31 vs. 83 months, p < 0.001) and RFS (9 vs. 20 months, p < 0.001) were significantly reduced in gastric resection. For the matched cohort, after excluding wedges, gastrectomy did not significantly decrease OS. However, RFS was decreased (11 vs. 20 months, p = 0.016). CONCLUSIONS: Despite high postoperative morbidity, when complete cytoreduction is achieved, the need for gastric resection is not associated with inferior long-term outcomes.

Preoperative Nutrition Status and Postoperative Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex surgery to treat peritoneal surface malignancy (PSM). PSM and gastrointestinal (GI) resection from CRS can lead to significant GI symptoms and malnutrition. There is limited research into the nutrition status of this patient group and the impact of malnutrition on morbidity. OBJECTIVE: This study aims to determine if preoperative malnutrition, assessed using the Subjective Global Assessment (SGA), is associated with postoperative morbidity and increased length of stay (LOS) in patients undergoing CRS/HIPEC for PSM. METHODS: This study prospectively assessed the nutritional status of patients undergoing CRS/HIPEC using a validated nutrition assessment tool. Preoperative clinical symptoms, Peritoneal Cancer Index (PCI), intraoperative blood transfusions, operative time, GI resections, postoperative morbidity, and LOS, as well as pre- and postoperative nutritional interventions, were recorded. The impact of preoperative nutritional status was assessed in relation to postoperative complications and hospital LOS. RESULTS: The study included 102 participants; 34 patients (33%) were classified as malnourished (SGA = B or C). Preoperative weight loss (15% vs. 74%; p ≤ 0.001) and the presence of clinical symptoms (18% vs. 47%; p = 0.002) were significantly higher in malnourished patients. While PCI, intraoperative blood transfusions, and GI resections were independent predictors of morbidity, malnutrition was significantly associated with infectious complications and LOS. For each grade of worsening malnutrition, LOS increased by an average of 7.65 days. CONCLUSIONS: Preoperative malnutrition is prevalent in patients undergoing CRS/HIPEC and postoperative morbidity is common. Malnutrition is linked to LOS and plays a role in postoperative outcomes such as infection. Clear pre- and postoperative nutrition pathways are needed to optimize nutrition support and postoperative recovery.

An analysis of the morbidity associated with abdominal wall resection and reconstruction after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

PURPOSE: CRS/HIPEC has evolved as an effective method for management of selected patients with peritoneal metastatic disease. Abdominal wall resection (AWR) is often required, and may require complex reconstructions, such as component separation (CST) leading to wound dehiscence (WD) and wound complications (WC). The purpose of our study was to analyse factors contributing to wound complications and wound recurrence (WR). METHODS: Retrospective review of a prospective database of 1074 patients undergoing CRS/HIPEC procedures from 1996 to 2017 at St George Hospital. RESULTS: AWR and reconstruction for abdominal wall metastases was performed in 197 (18.3%) patients. Tumour types included mesothelioma, appendiceal, colorectal and ovarian cancers. Grade III WC were found in 21 (10.6%). WD was found in 14 (7.1%) compared to 30 (3.4%) in 877 patients without AWR (p = 0.028). Midline WR was seen in 26 (13.3%) with AWR and mean time to recurrence of 18 months. Multivariable' regression analysis showed age (OR 1.06, 95%CI 1.01-1.11, p = 0.022) and CST (OR 9.63, 95%CI 2.55-36.23, p = 0.001) were independent predictors of Grade III WC, and CST (OR 4.19, 95%CI 1.27-13.86, p = 0.019) was an independent predictor of WD after AWR. The presence of a higher prior surgical score (PSS) 2-3 (OR 2.74, 95%CI 1.16-6.49, p = 0.022) was an independent predictor of midline WR post AWR. CONCLUSION: This study demonstrates that patients undergoing AWR have a higher incidence of postoperative WD. CST was associated with an increased incidence of Grade III WC and WD. Patients with a higher PSS were more likely to develop midline wound recurrence.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.

Long-term Survival and Propensity Score Matched Outcomes of Bilateral vs. Unilateral Diaphragm Interventions in Cytoreductive Surgery plus Intra-peritoneal Chemotherapy.

BACKGROUND/AIM: To assess the impact of short- and long-term outcomes of bilateral vs. unilateral diaphragm interventions in cyto-reductive surgery (CRS) and intra-peritoneal chemotherapy (IPC). PATIENTS AND METHODS: A total of 652 CRS/IPC procedures, between 1996 and 2018, required diaphragm interventions. Among these, 388 underwent bilateral intervention. Preoperative heterogeneity was assessed in 6 parameters and addressed with propensity score matching. The association of each respective analysis was assessed with 11 outcomes. Overall survival was assessed based on histology. RESULTS: CRS/IPC requiring bilateral diaphragmatic interventions illustrated significantly increased operative hours (9.6 vs. 8.6 hours, p<0.001). Postoperatively, there was significantly increased red blood cell (RBC) transfusion (6.37 units vs. 4.47 units, p=0.007) and grade III and IV complications (57.3% vs. 40.6%, p=0.004). No difference was noted in ICU stay, total length of stay, hospital death and return to OT. In terms of respiratory complications, an increased incidence of pneumothorax (16.5% vs. 6.2%, p<0.001) was noted whilst pleural effusions and pneumonia occurrences were non-significant. Overall survival, revealed bilateral interventions in low-grade appendiceal mucinous neoplasm conferred an increased relative risk (p=0.037, RR=2.230, 95%CI=1.052-4.730). They did not have an effect on OS in colorectal cancer and mesothelioma. CONCLUSION: Despite the increase in short-term morbidity, bilateral diaphragm interventions resulted in similar long-term survival to unilateral interventions.

Prevention of peritoneal recurrence in high-risk colorectal cancer and evidence of T4 status as a potential risk factor.

Peritoneal metastasis (PM) following primary resection of colorectal cancer is common. The combined use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has significantly improved the survival outcome of patients with colorectal PM (CRPM). Diagnosing and treating early PM is essential as its extent is correlated with poorer outcomes. There are two novel therapies - second-look surgery and synchronous hyperthermic intraperitoneal chemotherapy - that are proposed to prophylactically treat or intervene early in the disease process to reduce the incidence and adverse outcomes associated with PM. These strategies are limited to patients at high risk of developing CRPM, including those that had synchronous PM or ovarian metastases resected at primary tumour removal, or a perforated primary tumour. The data on advanced primary tumour (T4) as a prognostic factor for PM after primary resection suggest that T4a tumours are prognostically worse than T4b. This literature review outlines the evidence, feasibility and safety regarding the pre-emptive treatments, as well as the relevance of T4a tumours as a risk factor for metachronous CRPM.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported. METHODS: Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC. RESULTS: Of 260 patients included, those with low CEA/PCI ratio (<2.3) had longer median OS (56 vs 24 months, P = 0.001) and RFS (13 vs 9 months, P = 0.02). The prognostic impact of CEA/PCI ratio was most pronounced in patients with PCI ≤ 10 (OS of 72 vs 30 months, P < 0.001; RFS of 21 vs 10 months, P = 0.002). In multivariable analysis, elevated CEA/PCI ratio was independently associated with poorer OS (adjusted HR 1.85, 95%CI 1.11-3.10, P = 0.02) and RFS (adjusted HR 1.58, 95%CI 1.04-2.41, P = 0.03). CONCLUSION: CEA/PCI ratio is an independent prognostic factor for OS and RFS in CRPC. This novel approach allows both tumor activity and volume to be accounted for in one index, thus potentially providing a more accurate indication of tumor biological behavior.

Early postoperative intraperitoneal chemotherapy is associated with survival benefit for appendiceal adenocarcinoma with peritoneal dissemination.

INTRODUCTION: The combined approach of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has achieved encouraging outcomes for patients with PMCA with peritoneal dissemination. However, there is little evidence for the use of EPIC in addition to HIPEC in this group of patients. PATIENTS AND METHODS: This was a retrospective study of prospectively collected data of consecutive patients with PMCA who underwent CRS and perioperative intraperitoneal chemotherapy by one surgical team at St George Hospital in Sydney, Australia between Jan 1996 and Aug 2016. RESULTS: A total of 185 patients formed the cohort of this study. However, there was no significant difference in terms of hospital mortality (p = 0.632), major morbidity rate (i.e. Grade III/IV) (p = 0.444), intensive unit care stay (p = 0.638) and total hospital stay (p = 0.0.078). However, patients who received HIPEC and EPIC had a significant longer stay in high dependency unit (p < 0.001). Multivariate analysis showed combined HIPEC with EPIC is an independent prognostic factor for better overall survival (Hazard ratio (HR) = 0.42, 95% confidence interval (CI) = 0.19-0.92, P = 0.030) and disease free survival (HR = 0.66, 95%CI = 0.44-0.99, p = 0.045), adjusted for age, sex, peritoneal cancer index, completeness of cytoreduction score, CEA ≥ 6.5 mg/L, CA19-9 ≥ 24.0 U/mL and CA125 ≥ 32.0 U/mL. CONCLUSIONS: In summary, the combination of HIPEC and EPIC could potentially provide additional survival benefit for patients with PMCA with peritoneal spread as compared to HIPEC alone without increasing postoperative morbidity and mortality. More studies are warranted to further confirm the potential benefits of EPIC in PMCA and address the question of optimal drug and/or duration of EPIC.

CA 19-9 to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with epithelial appendiceal mucinous neoplasms and peritoneal dissemination undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

BACKGROUND: Serum tumour levels have been shown to be prognostic in patients with epithelial appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei (PMP)). A singular index which incorporates both tumour activity (as depicted by serum tumour marker levels) and tumour volume (as depicted by peritoneal carcinomatosis index (PCI)), may give a more precise surrogate of tumour biological behaviour. The prognostic implication of this index has not yet been reported. METHODS: A retrospective cohort study of all patients with PMP managed from 1996 to 2016 with cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) was performed by analysing the survival effect of the ratio of preoperative serum CEA, CA19.9 and CA125 to PCI. RESULTS: Three hundred and eighty-six patients were included. In patients with low-grade PMP, elevated CA19-9/PCI ratio resulted in poorer median overall survival times (104 months vs NR, 95%CI 83 - NR, log-rank p < 0.001) and was an independent predictor of reduced overall survival on multivariable analysis (adjusted HR 5.60, 95%CI 1.60-19.68, p = 0.007). In patients with high-grade PMP, no statistically significant difference in survival was recognised. CONCLUSION: CA19-9/PCI ratio is an independent prognostic factor for overall survival in patients with low-grade PMP undergoing CRS and IPC. By accounting for both tumour activity and tumour volume simultaneously, this novel index behaves as a surrogate of tumour biology and provides a useful adjunct for decisions regarding treatment allocation in this patient group.

Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.

BACKGROUND: It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. OBJECTIVE: This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. DESIGN: This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. SETTING: The study was conducted by 1 surgical team at St. George Hospital. PATIENTS: A total of 444 patients formed the cohort of this study. MAIN OUTCOME MEASURES: Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. RESULTS: Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p < 0.001), adjusted for peritoneal cancer index >20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. LIMITATIONS: This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. CONCLUSIONS: Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.

Synchronous liver resection with cytoreductive surgery for the treatment of liver and peritoneal metastases from colon cancer: results from an Australian centre.

BACKGROUND: Treatment of peritoneal metastases (PM) and liver metastases (LM) from colon cancer remains controversial. LM has been viewed as exclusion criterion for cytoreductive surgery (CRS) on the basis that such spread represents systemic disease. CRS and intraperitoneal chemotherapy (IPC) has gained increasing recognition as a treatment modality for selected patients with colon cancer and PM. This study analyses results of CRS and IPC for colon cancer and synchronous resection for treatment of LM and PM. METHODS: Seventy-eight patients with PM/LM colon cancer were analysed. Forty-two patients with PM were treated for disease limited to the peritoneum (A), and 36 patients received treatment for both PM and LM (B). Overall survival (OS), disease-free survival (DFS), morbidity, mortality and recurrence were compared. RESULTS: Median OS and DFS was 32.8 and 13.5 months. The median OS for A and B were 45.5 and 24.4 months respectively. Within B patients, 18 had a peritoneal carcinomatosis index (PCI) >7 and >3 LM and median survival of 21.8 months compared with 18 patients with PCI ≤7 and LM ≤3 with median survival of 38.4 months. Median DFS for A and B were 17.7 and 8.5 months respectively. Twenty-seven in total experienced major complications following surgery. Sixty-one patients recurred. Of A, 71.4% recurred compared with B at 86.1%. CONCLUSION: While our study is limited, it has demonstrated encouraging evidence that long-term survival outcomes can be achieved in this small but significant number of patients treated by CRS/IPC and additional synchronous liver resection with no significant increase in morbidity when compared with CRS/IPC alone.

Early Postoperative Intraperitoneal Chemotherapy for Low-Grade Appendiceal Mucinous Neoplasms with Pseudomyxoma Peritonei: Is it Beneficial?

BACKGROUND: There is little evidence for the use of early postoperative intraperitoneal chemotherapy (EPIC) in patients with low-grade appendiceal mucinous neoplasms (LAMNs) with pseudomyxoma peritonei (PMP). This study aims to assess the outcomes regarding the use of EPIC in a large cohort of patients with LAMNs with PMP uniformly treated by cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC), all of whom received hyperthermic intraperitoneal chemotherapy (HIPEC), and most of whom also received EPIC. METHODS: This was a retrospective study of prospectively collected data of consecutive patients with peritoneal carcinomatosis of appendiceal origin who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia, between January 1996 and November 2015. Subgroup analyses were performed for patients with a high Peritoneal Cancer Index (PCI) >20 and also based on histopathological subtypes of LAMNs. RESULTS: A total of 250 patients formed the cohort of this study. No significant differences were observed in terms of hospital mortality (p = 0.153), major morbidity rate (i.e., grade III/IV; p = 0.593), intensive care unit stay (p = 0.764), and total hospital stay (p = 0.927); however, patients who received HIPEC + EPIC had a significantly longer stay in the high dependency unit. Multivariate analysis showed combined HIPEC with EPIC is an independent prognostic factor for better survival outcomes (hazard ratio 0.30, 95 % confidence interval 0.12-0.74; p = 0.009), adjusted for age, PCI, and histopathological subtypes. CONCLUSIONS: The combination of HIPEC + EPIC can provide additional survival benefits for patients with LAMNs with PMP compared with HIPEC alone, without increasing postoperative morbidity and mortality. EPIC should be considered following CRS and HIPEC for patients with LAMNs with PMP.

Enterocutaneous fistula in patients with peritoneal malignancy following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Incidence, management and outcomes.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for peritoneal carcinomatosis (PC) from multiple origins, however is associated with increased complications compared to conventional gastrointestinal surgery. The aetiology of enterocutaneous fistulas (ECF) in most cases is a result of various contributing factors and therefore remains a major clinical problem, occurring in 4-34% of patients post-CRS. The aim of this study was to analyze the incidence and outcome of ECF following CRS/HIPEC. METHOD: From April 1999 to September 2015, 53 patients of 918 CRS/HIPEC procedures developed an ECF. Patient, operative and postoperative data were retrospectively analyzed to determine aetiology, classification outcome and possible contributing factors were reviewed on univariate and multivariate analysis. RESULTS: We report a 5.8% ECF rate, diagnosed at a median of 13 days. The mortality rate was 5.7% and other morbidity was significantly increased (p = 0.0001). Twenty-five (47.2%), 8 (15.1%) and 20 patients (37.7%) had low, moderate and high output ECF respectively. Patients that had a CC2 cytoreduction, abdominal VAC or smoked had a higher risk of fistula (p = 0.004, p < 0.0001, p = 0.008). Spontaneous closure was achieved in 49.2% with conservative treatment (median 29 days) and 33.9% underwent surgical intervention. Preoperative serum albumin <35 g/L (p = 0.04), PCI>17 (p = 0.025) and operation >8.6 h s (p = 0.001) were independent risk factors on multivariate analysis. Overall and 5-year survival was significantly reduced (p < 0.0001,p = 0.016). CONCLUSION: CRS/HIPEC remains an effective treatment modality for PC in selected patients with a comparable ECF incidence to reported elective gastrointestinal surgery rates. This study identifies multiple risk factors that should be considered in patients undergoing CRS/HIPEC.

Impacts of Preoperative Serum Albumin Level on Outcomes of Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy.

BACKGROUND: Only few small studies in the literature have explored the impacts of preoperative serum albumin level and clinical outcomes of patients with peritoneal surface malignancy (PSM) who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). This study aimed to evaluate the value of preoperative serum albumin as a prognostic factor for long-term survival outcomes after CRS and PIC in a large patient cohort and to determine whether preoperative serum albumin is correlated with perioperative complications. METHODS: This retrospective study examined prospectively collected data for patients with PSM who underwent CRS and PIC by one surgical team at St George Hospital in Sydney, Australia. The study used 35 g/L as the cuffoff for normal serum albumin level. RESULTS: The study enrolled 591 patients. Hypoalbuminemia was found to be associated with a significantly higher rate of major morbidity (p < 0.001), a longer ICU stay (p = 0.003), a longer HDU stay (p < 0.001), a longer total hospital stay (p < 0.001), and a shorter overall survival (OS) (p = 0.016). Factor analysis showed preoperative serum hypoalbuminemia to be a prognostic factor for a poor perioperative outcome (p = 0.018) and a poor OS (p = 0.026). CONCLUSION: Preoperative hypoalbuminemia is associated with poor perioperative outcomes. More importantly, it is a predictor of poorer OS for patients with PSM independent of the PCI, age, and completeness of cytoreduction. In the future, strategies should be undertaken to improve preoperative nutrition of malnourished patients as a means of improving clinical outcomes for patients with PSM.