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.

Exploring the practicality and acceptability a brief exercise communication and clinician referral pathway in cancer care: a feasibility study.

BACKGROUND: The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway. METHODS: Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken. RESULTS: Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care. CONCLUSIONS: Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.

External validation of prognostic scores and comparison of predictive accuracy for patients with colorectal cancer with peritoneal metastases considered for cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: Prognostic scores are developed to facilitate the selection of patients with colorectal cancer peritoneal metastases (CRPM) for treatment with cytoreductive surgery (CRS) ± intraperitoneal chemotherapy (IPC). Three prominent prognostic scores are the Peritoneal Surface Disease Severity Score (PSDSS), the Colorectal Peritoneal Metastases Prognostic Surgical Score (COMPASS), and the modified COloREctal-Pc (mCOREP). We externally validate these scores and compare their predictive accuracy. METHODS: Data from consecutive CRPM patients who underwent CRS/IPC from 1996 to 2018 was used to externally validate COMPASS, PSDSS, and mCOREP. Analysis evaluated the efficacy of each score in predicting (1) open-close laparotomy-those found at laparotomy to not be eligible for curative intent CRS/IPC, (2) surgical futility-those who underwent open-close laparotomy, palliative debulking surgery, or had an overall survival of less than 12 months, and (3) overall and recurrence-free survival (OS, RFS). RESULTS: Prognostic scores were calculated for the 174-patient external validation cohort. COMPASS was most accurate in predicting open-close laparotomy, futile surgery, and survival (OS and RFS). Area under the curve (AUC) for open-close prediction was 0.78 (95% confidence interval, CI: 0.68-0.87), representing useful discrimination. However, AUC for futility prediction was 0.62 (95% CI: 0.52-0.71), and C-statistic for OS was 0.65 indicating only possibly helpful discrimination. C-statistic for RFS was 0.59 indicating poor discrimination. CONCLUSION: While COMPASS showed the best statistical behavior, accuracy for several clinically relevant outcomes remains low, and thus applicability to clinical practice limited.

Use of Prognostic Factors and Scores in Selection of Patients with Colorectal Cancer Peritoneal Metastasis (CRPM) for Cytoreductive Surgery and Intraperitoneal Chemotherapy (CRS/IPC): Results of an International Survey Among Oncologic Clinicians.

BACKGROUND: No universally accepted guidelines exist for treatment of patients with colorectal cancer peritoneal metastases (CRPM) undergoing cytoreductive surgery and intraperitoneal chemotherapy (CRS/IPC). Several uncertainties remain concerning almost every aspect of this treatment modality, resulting in marked variability in patient management and likely outcomes. This survey aimed to define variations and trends in clinician decision making more clearly. METHODS: A 41-question web-based survey was distributed electronically via the Peritoneal Surface Oncology Group International (PSOGI), the International Society for the Study of Pleura and Peritoneum (ISSPP) as well as via social media (particularly Twitter). The survey sought to address and record clinician responses regarding patient workup/assessment, selection for preoperative systemic therapy, preoperative and intraoperative selection for CRS/IPC, and consideration of prognosis and complications. RESULTS: Complete responses were received from 60 clinicians from 45 centres in 22 countries. Upon assessment of survey responses, several interesting trends were noted in each section of the survey. Significant variability in surgeon practice and opinion were identified concerning almost every aspect of the treatment modality. CONCLUSION: This international survey provides the most comprehensive insight into clinician decision-making trends regarding patient assessment, selection and management. This should allow areas of variability to be more clearly defined and could potentially prompt development of initiatives for achieving consensus and standardisation of care in the future.

An exploratory survey study of disorder and its association with safety culture in four hospitals.

BACKGROUND: Signs of disorder in neighbourhoods (e.g., litter, graffiti) are thought to influence the behaviour of residents, potentially leading to violations of rules and petty criminal behaviour. Recently, these premises have been applied to the hospital context, with physical and social disorder found to have a negative association with patient safety. Building on these results, the present study investigates whether physical and social disorder differ between hospitals, and their relationship to safety culture. METHODS: We conducted a cross sectional survey with Likert-style and open response questions administered in four Australian hospitals. All staff were invited to participate in the pilot study from May to September 2018. An analysis of variance (ANOVA) was used to examine differences in disorder by hospital, and hierarchical linear regression assessed the relationship of physical and social disorder to key aspects of safety culture (safety climate, teamwork climate). Open responses were analysed using thematic analysis to elaborate on manifestations of hospital disorder. RESULTS: There were 415 survey respondents. Significant differences were found in perceptions of physical disorder across the four hospitals. There were no significant differences between hospitals in levels of social disorder. Social disorder had a significant negative relationship with safety and teamwork climate, and physical disorder significantly predicted a poorer teamwork climate. We identified five themes relevant to physical disorder and four for social disorder from participants' open responses; the preponderance of these themes across hospitals supported quantitative results. CONCLUSIONS: Findings indicate that physical and social disorder are important to consider in attempting to holistically understand a hospital's safety culture. Interventions that target aspects of physical and social disorder in a hospital may hold value in improving safety culture and patient safety.

Risk of opioid misuse in people with cancer and pain and related clinical considerations: a qualitative study of the perspectives of Australian general practitioners.

OBJECTIVE: To explore the perspectives of general practitioners (GPs) concerning the risk of opioid misuse in people with cancer and pain and related clinical considerations. DESIGN: A qualitative approach using semistructured telephone interviews. Analysis used an integrative approach. SETTING: Primary care. PARTICIPANTS: Australian GPs with experience of prescribing opioids for people with cancer and pain. RESULTS: Twenty-two GPs participated, and three themes emerged. Theme 1 (Misuse is not the main problem) contextualised misuse as a relatively minor concern compared with pain control and toxicity, and highlighted underlying systemic factors, including limitations in continuity of care and doctor expertise. Theme 2 ('A different mindset' for cancer pain) captured participants' relative comfort in prescribing opioids for pain in cancer versus non-cancer contexts, and acknowledgement that compassion and greater perceived community acceptance were driving factors, in addition to scientific support for mechanisms and clinical efficacy. Participant attitudes towards prescribing for people with cancer versus non-cancer pain differed most when cancer was in the palliative phase, when they were unconcerned by misuse. Participants were equivocal about the risk-benefit ratio of long-term opioid therapy in the chronic phase of cancer, and were reluctant to prescribe for disease-free survivors. Theme 3 ('The question is always, 'how lazy have you been?') captured participants' acknowledgement that they sometimes prescribed opioids for cancer pain as a default, easier option compared with more holistic pain management. CONCLUSIONS: Findings highlight the role of specific clinical considerations in distinguishing risk of opioid misuse in the cancer versus non-cancer population, rather than diagnosis per se. Further efforts are needed to ensure continuity of care where opioid prescribing is shared. Greater evidence is needed to guide opioid prescribing in disease-free survivors and the chronic phase of cancer, especially in the context of new treatments for metastatic disease.

Volume-Time Index Is Not an Indicator of Outcome for Patients Undergoing CRS/HIPEC for Treatment of High-Grade Appendiceal Carcinomatosis.

BACKGROUND/AIM: Completeness of cytoreduction score (CC-score) and tumour grade have been shown to be independent prognostic factors in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of high-grade appendiceal carcinomatosis (PMCA). In patients with colorectal cancer with peritoneal metastases (CRPM) that undergo CRS/HIPEC, volume time index (VTI) has been shown to be an independent prognostic factor for overall survival (OS). This analysis was conducted to evaluate VTI as a prognostic factor in PMCA. PATIENTS AND METHODS: We performed A retrospective cohort study of 131 patients who underwent CRS-HIPEC for PMCA from 1996 to 2017. VTI was calculated and analyses were performed to determine the association with patients' outcomes. RESULTS: Median overall survival by high vs. low VTI groups were 69 months (95%CI=45-NA) vs. 63 months [95% Confidence Interval (CI)=48-not available (NA)], with an associated difference in 5-year survival rates of 52.1 (95%CI=39.5-68.8) vs. 50.6 (95%CI=35.2-72.6) respectively, with a non-significant p-value of 0.968. For the 82 patients with complete recurrence data, the median RFS stratified by high vs. low VTI were 16 months (95%CI=10-25) vs. 20 months (95%CI=13-34) respectively, with no statistically significant difference in 5-year recurrence-free survival (RFS). CONCLUSION: VTI for PMCA was not shown to be correlated with overall survival (OS) for patients undergoing CRS/HIPEC, and suggests that the rate of tumour growth does not affect the patients' outcome. Neither high PCI nor rapid tumour growth following primary tumour resection should, therefore, be a contraindication for CRS/HIPEC in patients with PMCA.

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.

Impact of Concomitant Urologic Intervention on Clinical Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: The impact of concomitant urologic procedures (UPs) on perioperative and long-term outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is uncertain. METHODS: In total, 935 consecutive CRS/HIPEC procedures were performed between 1996 and 2016 in Sydney, Australia. Among these, 73 (7.8%) involved concomitant UP. The association of concomitant UP with 21 perioperative outcomes and overall survival was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring UP were more likely to require transfusion of ≥5 units of red blood cells (P=0.031) and have a complete cytoreduction (79% vs. 60%, P<0.001). On multivariate analysis, UP was not associated with in-hospital mortality (2.7% vs. 1.7%, P=0.407) or grade III/IV morbidity (52% vs. 41%, P=0.376). The incidence of ureteric fistula (4% vs. 1%, P=0.004), return to theater (26% vs. 14%, P=0.005) and digestive fistula (22% vs. 11%, P=0.005) was higher in the UP group. The addition of a UP did not significantly impact overall survival for appendiceal cancer (P=0.162), colorectal cancer (P=0.315), or pseudomyxoma peritonei (P=0.120). CONCLUSIONS: Addition of a UP was not associated with an increased risk of grade III/IV morbidity or poorer long-term survival after CRS/HIPEC.

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.

Recurrence and Survival Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Small Bowel Adenocarcinoma.

BACKGROUND: Peritoneal dissemination of small bowel adenocarcinoma (SBA) is rare but is associated with a dismal prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising treatment option. We evaluated our experience of CRS-HIPEC for the treatment of SBA. PATIENTS AND METHODS: Sixteen consecutive patients underwent CRS-HIPEC for small bowel malignancy between 2003 and 2016. Clinopathological and treatment-related factors were obtained from a prospective database. The study's endpoints of disease-free (DFS) and overall (OS) survival were evaluated using the Kaplan-Meier method. Prognostic variables were identified through univariate and multivariate analyses. RESULTS: Follow-up was complete in all patients. The median follow-up was 20.6 (range=0.2-62) months. The was no in-hospital mortality and grade III/IV morbidity was 25%. The median OS after CRS-HIPEC was 24.7 months, with a 36-month survival of 34%. The median DFS was 11.3 months, with a 36-month DFS of 8%. Two factors were associated with a poorer OS on univariate analysis; only peritoneal cancer index >10 was associated with a poorer OS on multivariate analysis (p=0.032). CONCLUSION: CRS-HIPEC in selected patients with peritoneal dissemination of SBA is associated with reasonable mid-term survival outcomes but treatment failure is common. High disease burden, quantified by the PCI is associated with poor outcomes. A large, prospective, multi-institutional study is needed to further evaluate the outcomes of CRS-HIPEC for SBA.

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.

Allogenic Blood Transfusion Is an Independent Predictor of Poorer Peri-operative Outcomes and Reduced Long-Term Survival after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a Review of 936 Cases.

INTRODUCTION: There is a paucity of data on the impact of allogenic blood transfusion (ABT) on morbidity and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 at a high-volume institution in Sydney, Australia. Of these, 337(36%) patients required massive ABT (MABT) (≥5 units). Peri-operative complications were graded according to the Clavien-Dindo classification. The association of concomitant MABT with 21 peri-operative outcomes and overall survival (OS) was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring MABT had more extensive disease as reflected by a higher peritoneal cancer index (≥17) (70 vs. 29%, p < 0.001) and longer operative times (≥9 h) (82 vs. 35%, p < 0.001). After accounting for confounding factors, MABT was associated with in-hospital mortality (relative risk (RR), 7.72; 95% confidence interval (CI), 1.35-10.11; p = 0.021) and grade III/IV morbidity (RR, 2.05; 95% CI, 1.42-2.95; p < 0.001). MABT was associated with an increased incidence of prolonged hospital stay (≥28 days) (RR, 1.86; 95% CI, 1.26-2.74; p = 0.002) and intensive care unit stay (≥4 days) (RR, 1.83; 95% CI, 1.24-2.70, p = 0.002). It was also associated with a significant OS in patients with colorectal cancer peritoneal carcinomatosis (RR 4.49; p < 0.001) and pseudomyxoma peritonei (RR, 4.37; p = 0.026), but not appendiceal cancer (p = 0.160). CONCLUSION: MABT is an independent predictor for poorer peri-operative outcomes including in-hospital mortality and grade III/IV morbidity. It may also compromise long-term survival, particularly in patients with colorectal cancer peritoneal carcinomatosis.

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.