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.

Health related quality of life is excellent and sustained at two decades after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in survivors of pseudomyxoma peritonei of appendiceal origin.

INTRODUCTION: Optimal management of pseudomyxoma peritonei (PMP) is by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), which can achieve 20-year disease-free, and overall survival. There is limited information on the health-related quality of life (HRQOL) of PMP survivors beyond five years. We report longitudinal HRQOL in patients with PMP of appendiceal origin up to 17-years after their CRS and HIPEC in 2003-2004. METHODS: Patients had HRQOL assessed with EORTC QLQ-C30 questionnaires pre-operatively, and at 1-, 10- and 17-years post-operatively. Comparisons in global health-related QOL (global-HRQOL) measures were made with (1) an age- and sex-matched normal European population, (2) between patients who underwent complete cytoreduction (CRS CC0/1) versus maximal tumor debulking (MTD), and (3) between those with and without peritoneal recurrence. RESULTS: Forty-six patients underwent CRS & HIPEC for appendiceal PMP. One patient withdrew from the study. Of the 45 patients, 23 patients were alive at ten and 15 patients at 17-years post-operatively. 21/23 (91%) and 14/15 patients (93%) completed questionnaires respectively. Pre-operatively, patients had significantly lower global-HRQOL compared with the reference population. Over follow-up, patients experienced improvements in their global-HRQOL. By post-operative year-10 and -17, there was no difference between the global-HRQOL of patients and reference population. As expected, patients with CC0/1 and without peritoneal tumor recurrence had better global-HRQOL at ten- and 17-years post-operatively compared with those with MTD or recurrence. CONCLUSIONS: Optimal CRS and HIPEC is an effective treatment for appendiceal PMP that can achieve long-term survival. HRQOL is excellent and maintained, in those who have CC0/1 without recurrence.

Development and Validation of Nomograms to Predict Survival in Patients Undergoing Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei of Appendiceal Origin.

Importance: Pseudomyxoma peritoni, a rare condition characterized by mucinous ascites and peritoneal deposits, mainly originates from a ruptured mucinous appendix tumor and is considered an indolent disease but can progress and become fatal. Optimal treatment to improve cure and survival rates involves complete cytoreductive surgery (CCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Accurate predictive models are useful in supporting and informing treatment strategies and stratifying patient follow-up. Objective: To evaluate the prognostic significance of clinically important variables and generate validated nomograms to predict overall (OS) and disease-free survival (DFS) following CCRS and hyperthermic intraperitoneal HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin. Design, Setting, and Participants: This retrospective study used prospectively collected data on patients who had cytoreductive surgery (CRS) and HIPEC in a single institution between 1994 and 2018. The cohort was randomly allocated into development (70%) and validation (30%) sets. Univariate and multivariate analyses were performed with Cox proportional hazards regression. Main Outcomes and Measures: A prediction model was developed with significant prognostic factors identified by multivariate analysis. The model's prognostic performance was evaluated with the concordance index (C index). The nomogram was calibrated by comparing the predicted and observed probabilities. Results: Of 2637 CRS and HIPEC operations, 1102 patients (female, 64.4%; median age [IQR], 57.0 [48.0-66.0] years) (41.8%) had CCRS for PMP of appendiceal origin. Elevated tumor markers, peritoneal carcinomatosis index, gastrectomy, and tumor grade were independent predictive factors for DFS. Gender, age, elevated tumor makers, peritoneal carcinomatosis index, and tumor grade influenced OS. The nomograms were generated with respective prognostic factors. The nomograms showed good performance in predicting survival. Median OS of the cohort was 16.5 years (95% CI, 13.7-19.2) with a 5-year probability of survival of 80.2%. The median DFS was 10.3 years (95% CI, 7.2- 13.3) and the 5-year probability of recurrence-free survival was 60.5%. Conclusions and Relevance: Clinically important independent predictors for survival and recurrence were selected to develop the nomograms for OS and DFS. These 2 nomograms are user friendly and useful tools for patient management with clinical trial design applications.

First Report With Medium-term Follow-up of Intestinal Transplantation for Advanced and Recurrent Nonresectable Pseudomyxoma Peritonei.

OBJECTIVE: To report our experience with the combination of radical surgical excision and intestinal transplantation in patients with recurrent pseudomyxoma peritonei (PMP) not amenable to further cytoreductive surgery (CRS). BACKGROUND: CRS and heated intraoperative peritoneal chemotherapy are effective treatments for many patients with PMP. In patients with extensive small bowel involvement or nonresectable recurrence, disease progression results in small bowel obstruction, nutritional failure, and fistulation, with resulting abdominal wall failure. METHODS: Between 2013 and 2022, patients with PMP who had a nutritional failure and were not suitable for further CRS underwent radical debulking and intestinal transplantation at our centre. RESULTS: Fifteen patients underwent radical exenteration of affected intra-abdominal organs and transplantation adapted according to the individual case. Eight patients had isolated small bowel transplantation and 7 patients underwent modified multivisceral transplantation. In addition, in 7 patients with significant abdominal wall tumor involvement, a full-thickness vascularized abdominal wall transplant was performed. Two of the 15 patients died within 90 days due to surgically related complications. Actuarial 1-year and 5-year patient survivals were 79% and 55%, respectively. The majority of the patients had significant improvement in quality of life after transplantation. Progression/recurrence of disease was detected in 91% of patients followed up for more than 6 months. CONCLUSION: Intestinal/multivisceral transplantation enables a more radical approach to the management of PMP than can be achieved with conventional surgical methods and is suitable for patients for whom there is no conventional surgical option. This complex surgical intervention requires the combined skills of both peritoneal malignancy and transplant teams.

Age alone is not a barrier to efficacy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: analysis of 1138 patients from the UK and Ireland Colorectal Peritoneal Metastases Registry.

BACKGROUND: The management of colorectal peritoneal metastases continues to be a challenge but recent evidence suggests cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve survival. Uncertainty about the relationship between age and tumour biology makes patient selection challenging particularly when reported procedure related morbidity is high and impact on survival outcomes unknown. The UK and Ireland Colorectal Peritoneal Metastases Registry was reviewed to assess the influence of age on efficacy of CRS and HIPEC. METHODS: A review of outcomes from the UK and Ireland Colorectal Peritoneal Metastases Registry was performed. Data from 2000 to 2021 were included from five centres in the UK and Ireland, and the cohort were sub-divided into three age groups; <45 years, 45-65 years and >65 years old. Primarily, we examined post-operative morbidity and survival outcomes across the three age groups. In addition, we examined the impact that the completeness of cytoreduction, nodal status, or adverse pathological features had on long-term survival. RESULTS: During the study period, 1138 CPM patients underwent CRS HIPEC. 202 patients(17.8%) were <45 years, 549 patients(48.2%) aged 45-65 years and 387 patients(34%) >65 years. Overall, median length of surgery (CRS and HIPEC), median PCI score and rate of HIPEC administration was similar in all three groups, as was overall rates of major morbidity and/or mortality. Complete cytoreduction rates (CC0) were similar across the three cohorts; 77%, 80.6% and 81%, respectively. Median overall survival for all patients was 38 months following complete cytoreduction. CONCLUSION: Age did not appear to influence morbidity or long-term survival following CRS and HIPEC. When complete cytoreduction is achieved survival outcomes are good. The addition of HIPEC can be performed safely and may reduce local recurrence within the peritoneum.

Assessment of the 2020 NICE criteria for preoperative radiotherapy in patients with rectal cancer treated by surgery alone in comparison with proven MRI prognostic factors: a retrospective cohort study.

BACKGROUND: Selection of patients for preoperative treatment in rectal cancer is controversial. The new 2020 National Institute for Health and Care Excellence (NICE) guidelines, consistent with the National Comprehensive Cancer Network guidelines, recommend preoperative radiotherapy for all patients except for those with radiologically staged T1-T2, N0 tumours. We aimed to assess outcomes in non-irradiated patients with rectal cancer and to stratify results on the basis of NICE criteria, compared with known MRI prognostic factors now omitted by NICE. METHODS: For this retrospective cohort study, we identified patients undergoing primary resectional surgery for rectal cancer, without preoperative radiotherapy, at Basingstoke Hospital (Basingstoke, UK) between Jan 1, 2011, and Dec 31, 2016, and at St Marks Hospital (London, UK) between Jan 1, 2007, and Dec 31, 2017. Patients with MRI-detected extramural venous invasion, MRI-detected tumour deposits, and MRI-detected circumferential resection margin involvement were categorised as MRI high-risk for recurrence (local or distant), and their outcomes (disease-free survival, overall survival, and recurrence) were compared with patients defined as high-risk according to NICE criteria (MRI-detected T3+ or MRI-detected N+ status). Kaplan-Meier and Cox proportional hazards analyses were used to compare the groups. FINDINGS: 378 patients were evaluated, with a median of 66 months (IQR 44-95) of follow up. 22 (6%) of 378 patients had local recurrence and 68 (18%) of 378 patients had distant recurrence. 248 (66%) of 378 were classified as high-risk according to NICE criteria, compared with 121 (32%) of 378 according to MRI criteria. On Kaplan-Meier analysis, NICE high-risk patients had poorer 5-year disease-free survival compared with NICE low-risk patients (76% [95% CI 70-81] vs 87% [80-92]; hazard ratio [HR] 1·91 [95% CI 1·20-3·03]; p=0·0051) but not 5-year overall survival (80% [74-84] vs 88% [81-92]; 1·55 [0·94-2·53]; p=0·077). MRI criteria separated patients into high-risk versus low-risk groups that predicted 5-year disease-free survival (66% [95% CI 57-74] vs 88% [83-91]; HR 3·01 [95% CI 2·02-4·47]; p<0·0001) and 5-year overall survival (71% [62-78] vs 89% [84-92]; 2·59 [1·62-3·88]; p<0·0001). On multivariable analysis, NICE risk assessment was not associated with either disease-free survival or overall survival, whereas MRI criteria predicted disease-free survival (HR 2·74 [95% CI 1·80-4·17]; p<0·0001) and overall survival (HR 2·44 [95% CI 1·51-3·95]; p=0·00027). 139 NICE high-risk patients who were defined as low-risk based on MRI criteria had similar disease-free survival as 118 NICE low-risk patients; therefore, 37% (139 of 378) of patients in this study cohort would have been overtreated with NICE 2020 guidelines. Of the 130 patients defined as low-risk by NICE guidelines, 12 were defined as high-risk on MRI risk stratification and would have potentially been missed for treatment. INTERPRETATION: Compared to previous guidelines, implementation of the 2020 NICE guidelines will result in significantly more patients receiving preoperative radiotherapy. High-quality MRI selects patients with good outcomes (particularly low local recurrence) without radiotherapy, with little margin for improvement. Overuse of radiotherapy could occur with this unselective approach. The high-risk group, with the most chance of benefiting from preoperative radiotherapy, is not well selected on the basis of NICE 2020 criteria and is better identified with proven MRI prognostic factors (extramural venous invasion, tumour deposits, and circumferential resection margin). FUNDING: None.

Early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in 632 patients with pseudomyxoma peritonei of appendiceal origin: A single institution experience.

BACKGROUND: There is ongoing controversy concerning the indications and benefits of early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with pseudomyxoma peritonei. The main contra-indications preventing wide-spread use of EPIC are reports of an increased postoperative morbidity with no clear evidence of oncological benefit. This paper reports a single high volume institution experience with EPIC over a 25-year period. METHODS: This is a retrospective analysis of a single institution prospective database of patients undergoing CRS and HIPEC for appendiceal neoplasms from March 1994 to December 2019. Sub group analysis of patients who received EPIC with 5FU 15mg/m2 is reported and compared with patients who did not receive EPIC. RESULTS: Overall, 632/1564 (40%) received EPIC. Patients who received EPIC were younger (median age 55 (IQR 45-63) vs 59 (IQR 50-68)) with similar extent of disease to those who did not have EPIC. EPIC was more likely to be given after complete cytoreduction. The use of EPIC has reduced over the last 25 years from 78% of patients initially to 16% most recently. Length of stay in critical care and total hospital stay were longer in patients who received EPIC but surprisingly major morbidity (Clavien Dindo Grade >3) was lower (p = 0.001). CONCLUSION: EPIC can be administered safely following CRS and HIPEC for PMP of appendix origin when used in carefully selected patients in a high-volume centre. Randomised trials are needed to establish impact on disease free and overall survival to optimize selection criteria.

Overall Survival is More Closely Associated with Peritoneal than Primary Appendiceal Pathological Grade in Pseudomyxoma Peritonei with Discordant Pathology.

BACKGROUND: The WHO classification of mucinous appendix neoplasms and pseudomyxoma peritonei (PMP) describes low- and high-grade histology and is of prognostic importance. The metastatic peritoneal disease grade can occasionally be different from the primary appendix tumor. This analysis aimed to report outcomes from a high-volume center in patients with pathological discordance. METHODS: This was a retrospective analysis of prospective data of patients treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP at a single institution between January 2016 and December 2020. Reporting was by pathologists with a special interest in peritoneal malignancy. Discordant pathology was classified as a low-grade primary appendix tumor with high-grade peritoneal disease, or a high-grade primary appendix tumor with low-grade peritoneal disease. Outcomes analyzed were overall and recurrence-free survival, and Kaplan-Meier survival curves and the log-rank test were used to analyze the outcomes. RESULTS: Between 2016 and 2020, 830 patients underwent CRS and HIPEC for PMP, of whom 37 (4.4%) had discordant pathology. The primary appendix tumors were low-grade in 23 patients and high-grade in 14 patients. The median Peritoneal Cancer Index (PCI) was significantly higher in patients with a low-grade primary tumor (31 vs. 16; p = 0.001), while complete cytoreduction (CC0/1) was achieved in 31/37 (83.8%) patients. The median follow-up was 19 months. Overall survival was worse in those with high-grade peritoneal disease (p = 0.029), whereas recurrence-free survival was similar in both groups (p = 0.075). CONCLUSION: In PMP with pathological discordance, the peritoneal disease grade influences prognosis and survival.

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.

Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Early Results from a Prospective Cohort Study of 115 Patients.

BACKGROUND: This study aimed to describe short- and medium-term longitudinal quality-of-life (QoL) outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Consecutive patients undergoing CRS and HIPEC were recruited. The primary outcome was QoL, measured using the short-form 36 questionnaire and expressed as a physical component score (PCS) and a mental component score (MCS), with higher scores representing better QoL. Data were collected prospectively at baseline and before discharge, then 3, 6, and 12 months postoperatively. Trajectories of the PCS and MCS were described for the study period and grouped according to a peritoneal carcinomatosis index (PCI) (≤ 12 vs. ≥ 13) and a completeness of cytoreduction (CC) score (CC0 vs. CC1-CC3). RESULTS: Overall, 117 patients underwent CRS and HIPEC and 115 (98.3%) of the 117 patients participated in the study. The main primary pathology was colorectal in 52 (45%) of the 115 patients and appendiceal in 27 (23.5%) of the 115 patients. The median baseline PCS [48.16; interquartile range (IQR), 38.6-54.9] had decreased at pre-discharge (35.34; IQR, 28.7-41.8), then increased slightly at 3 months (42.54; IQR, 37.6-51.6), before returning to baseline within 6 months (48.35; IQR, 39.1-52.5) and remaining unchanged 12 months after surgery (48.55; IQR, 40.8-55.5). The MCS remained unchanged during the study period. The patients with a PCI of 13 or higher had worse PCS and MCS during the postoperative period than the patients with a PCI of 12 or lower. CONCLUSIONS: The CRS and HIPEC procedures impaired PCS, with scores returning to baseline within 6 months after surgery, whereas MCS remained unchanged. The patients with a lower PCI had better postoperative QoL outcomes. For patients with peritoneal malignancy, CRS and HIPEC can be performed with acceptable short- to medium-term QoL outcomes.

Accelerating the learning curve in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy using an external mentor model.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an accepted therapeutic approach in selected patients with peritoneal malignancy. The aim of this study was to describe early outcomes in the first 50 patients managed with CRS and HIPEC in a newly established peritoneal malignancy centre in Sydney, Australia, under the guidance of an experienced peritoneal malignancy mentor. METHODS: This is a retrospective review of a prospective maintained database of early outcomes in the first 50 patients who underwent CRS and HIPEC between April 2017 and April 2018 at a newly established peritoneal malignancy centre. Type of primary, surgery time, length of hospital stay, blood loss, peritoneal carcinomatosis index, completeness of surgery, complications, recurrence rate and 30-day mortality were reviewed. RESULTS: A total of 135 patients were referred and reviewed at the multidisciplinary team meeting with 50 (26 male) patients undergoing CRS and HIPEC. Of these 50 patients, 47 (94%) underwent complete cytoreduction while three (6%) had maximal tumour debulking surgery. Tumour pathology was of appendix origin (44%) and colorectal peritoneal metastases (44%). Median surgical time was 7.4 h (interquartile range 5.7-10.0). Median length of hospital stay was 13 days (interquartile range 9.7-19.0). Six (12%) patients experienced a grade III or IV Clavien-Dindo complication. There was no 30-day mortality. CONCLUSION: This study reports the successful establishment of a peritoneal malignancy centre under the guidance of an experienced peritoneal malignancy mentor. The short-term surgical outcomes observed in the first 50 cases are promising and comparable to other more experienced centres.

Increased Incidence of Central Venous Catheter-Related Infection in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intra-Peritoneal Chemotherapy.

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line sepsis is one of a number of potential morbidities. The aim of this study was to calculate the incidence of catheter-related infection (CRI) in a CRS and HIPEC patient population and to assess its influence on length of hospital stay. Methods: Data were collected on consecutive patients who underwent CRS HIPEC between August 2013 and October 2017. Data included patient demographics, timing of CVC insertion/removal, time spent in critical care, and CVC tip/blood culture results. Charts were reviewed for patients with both positive CVC culture and positive blood cultures to assess for evidence of catheter related infection and systemic inflammatory response syndrome (SIRS). Results: Data on 100 consecutive CRS HIPEC operations performed between August 2013 and October 2017 was analyzed. There were 11 CRIs in 100 CVCs, resulting in a CRI rate of 16.2 per 1,000 CVC days. Patients within the CRI group had a longer high-dependency unit (HDU) stay compared with the non-septic group (6 days vs. 4.07 days, p < 0.05). The CVC duration for the CRI and non-CRI group was 8.4 and 7.6 days, respectively (p = 0.12). The CRI group also had an increased total hospital length of stay (LOS; 20.8 days vs. 15.4 days, p < 0.05). On average, CRIs occurred eight days post-operative and four days post-HDU discharge. There was no association identified with longer CVC duration (p = 0.34). There has been an annual decline in CRI rates in CRS and HIPEC patients over the duration of the study period from 19.1 per 1,000 CVC days in 2016 to 8.2 per 1,000 CVC days in 2017. Conclusion: This is the first study to report on CRI rates in patients undergoing CRS and HIPEC. The CRI rate of 16.2 per 1,000 CVC days is higher than the overall national figure of 5.2 per 1,000 for CVC lines inserted in the operating room. Patients who developed line sepsis had longer HDU and longer overall hospital stay. Catheter-related infection was noted post-HDU discharge in all cases. Implementation of a CVC care bundle in the later years of the study period coincided with a reduction in CRI rates.

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.

Single centre guidelines for radiological follow-up based on 775 patients treated by cytoreductive surgery and HIPEC for appendiceal pseudomyxoma peritonei.

AIM: Pseudomyxoma peritonei (PMP) is an uncommon malignancy, generally originating from a ruptured epithelial tumour of the appendix. Despite successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), some patients recur. Currently there are no guidelines on the methods, frequency and intensity of follow-up. METHODS: Between 1994 and 2016, 1070 patients underwent surgery for a perforated epithelial tumour of the appendix, predominantly with PMP. Overall (OS) and Disease Free Survival (DFS) were documented by annual CT scanning and evaluated according to the Kaplan-Meier method. The influence of histological differentiation was investigated. RESULTS: Overall, 775/1070 (72%) had complete cytoreductive surgery (CCRS) and HIPEC. Histological classification was low grade PMP in 615 (79.4%), high grade PMP in 134 (17.3%) and adenocarcinoma in 26 (3.4%). DFS and OS were significantly worse for high grade disease, with the steepest decline for both in the first three years. DFS curves, for low as well as high grade PMP, levelled off at year 6 at approximately 60% and 20% respectively. Thereafter there were few recurrences in either group. CONCLUSION: Annual CT of the abdomen and pelvis in the first six years appears to be adequate follow-up for low grade PMP. In high grade PMP, additional imaging of the chest and more frequent surveillance, during the first three years postoperatively, may detect recurrent disease earlier. From year 6 on, reduced frequency of follow-up is proposed, independent of the histology. This long-term follow-up in a large number of patients gives insight into tumour behavior after CCRS and HIPEC for PMP and guides intensity of surveillance.

Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre. METHODS: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016. RESULTS: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49 years (range 21-73 years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2-115.4) and 58.8 (47.4-70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival. CONCLUSION: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.

The pre-operative neutrophil-lymphocyte ratio predicts overall and disease-free survival following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with pseudomxyoma peritonei of appendiceal origin.

AIM: The neutrophil-lymphocyte ratio (NLR) and other inflammation-based scores have been used as a prognostic tool to predict survival in solid tumours including pseudomyxoma peritonei (PMP). The aim was to evaluate the prognostic value of this marker and risk stratify PMP patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Retrospective analysis was conducted of a prospectively collected database of patients with PMP who underwent CRS and HIPEC between 1994 and 2015. The NLR was calculated by dividing the pre-operative neutrophil count by lymphocyte count. Predicted overall survival (OS) and disease-free interval (DFI) were calculated using a Kaplan-Meier survival model. RESULTS: The study included 699 patients, stratified into four groups as defined by their NLR. Group A: 200 (28.6%) patients (NLR = 0.10-2.00), Group B: 160 (22.8%) patients (NLR = 2.10-2.78), Group C: 184 (26.3%) patients (NLR = 2.79-4.31) and Group D: 155 (22.2%) patients (NLR ≥ 4.32). The median follow-up for this cohort was 36 months. The predicted DFI was 132.2, 113.1, 84.4 and 47.9 months and the OS was 141.1, 117.6, 88.7 and 51.2 months for Groups A, B, C and D, respectively. As the NLR increases, there is a reduction in long-term survival. CONCLUSION: The pre-operative NLR is cost effective and has equivalent prognostic value to pre-operative tumour markers for patients with PMP treated with CRS and HIPEC. The NLR is a reliable tool that may have a role in predicting outcomes following CRS and HIPEC for patients with PMP of appendiceal origin.