Personalising care for patients: implementing a treatment summary folder following cytoreductive surgery.

BACKGROUND: A patient survey highlighted that patients treated with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) at one NHS trust lacked confidence with the transition of care between teams. A personalised folder of treatment information was designed and given to patients prior to discharge. AIMS: To obtain patient feedback on the implementation and content of the folder. METHODS: 30 consecutive patients were given the folder at discharge. Participants completed an online questionnaire to determine whether the information in the folder was appropriate, given at the right time in the pathway and enhanced confidence on discharge. FINDINGS: 90% response rate was achieved. Of the respondents, 96% strongly agreed/agreed that the folder was helpful, 4% disagreed; 92% strongly agreed/agreed that the amount of information was right, 8% preferred more information, none less; 74% agreed/strongly agreed that the folder was provided at the right time; 96% said that the content met their expectations. CONCLUSION: Patients treated with CRS and HIPEC have specific needs related to their treatment. Implementation of the patient information folder at discharge increases patient confidence.

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.

Indications and long-term outcomes of preoperative inferior vena caval filters in 111 patients at high risk of pulmonary embolism undergoing major abdominal surgery.

AIMS: Patients with abdominal cancer requiring major surgical intervention are at high risk of venous thromboembolic events (VTE), particularly pulmonary emboli (PE). A proportion of patients with cancer can present with, or have had, major VTEs prior to definitive surgical treatment. Preoperative percutaneous inferior venal caval filters (IVCF) may reduce the risk of PE. The aim of this study was to assess the indications, complications, retrieval rates, and long-term outcome of IVCFs in patients undergoing major abdominal surgery. METHODS: This was a retrospective analysis of a prospective IVCF database between 2007 and 2018 of all patients with IVCF insertion prior to major abdominal surgery. The indications for an IVCF, procedural complications and surgical interventions were recorded. RESULTS: Overall, 111 patients had IVCF insertion. IVCF placement failed in one patient with gross abdominal disease. Indications for an IVCF were: prior PE in 65/111 (59%) and major vein thrombus in 42 (38%). Overall, 26/111 (23%) had the IVCF removed at a median of 91 days. In two patients IVCF removal failed. At follow-up of the 85 patients who had the IVCF left in situ, six developed filter-related thrombus and 13 a deep vein thrombosis (DVT). Four patients had a PE with an indwelling IVCF. CONCLUSION: Preoperative IVCF may reduce perioperative PE in patients at high risk of thrombosis undergoing major abdominal surgery where early anticoagulation is contraindicated. Long-term follow-up of retained IVCF suggests that major problems are infrequent, though further thrombosis may occur and long-term anticoagulation may be needed.

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.

Perforated Colorectal Cancer.

The majority of patients with colorectal tumors will present via the elective route. However, one-fifth of patients will present as an emergency. The most common cause of emergency presentation of colorectal cancer is obstruction followed by perforation, and in many cases, patients will present with both. We discuss the management of the patient presenting with a perforated colorectal tumor covering the acute presentation and also how to deal with consequences of a perforated tumor, namely, the management of colorectal peritoneal metastasis (CPM). CPM used to be considered a terminal condition; however, a strategy of early detection of CPM, careful patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, leads to much improved outcomes and even cure, in some patient compared with systemic chemotherapy alone.

Hepatobiliary and pancreatic procedures during cytoreductive surgery and HIPEC.

PURPOSE: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been used as locoregional treatment in selected patients with peritoneal malignancy. The purpose of this study was to report on the outcomes of patients undergoing hepatobiliary and pancreatic procedures during CRS and HIPEC. METHODS: A prospectively maintained database was used to identify patients that underwent hepatobilliary and/or pancreatic procedures during CRS and HIPEC. Outcome variables included morbidity, 30-day or in-hospital mortality, return to operating theatre, and complications. RESULTS: Sixty eight patients were included in the study, in whom 67 hepatobiliary and 15 pancreatic procedures were performed. Complete cytoreduction (CC-0/1) was achieved in 64 patients (94.8%). Twelve patients underwent liver resections, 50 underwent resection of Glisson's capsule, 5 underwent procedures of the biliary tree and 15 patients underwent pancreatic procedures. Major complications were encountered in 30/68 patients (44.1%). Pancreatic fistulas (PFs) were observed in 42.8% of the patients that underwent distal pancreatectomy. Reoperation rate was 8.8%, while 2.9% of the patients died during their hospital stay. CONCLUSION: The need for hepatobiliary procedures bears a significant - but acceptable - rate of morbidity. However, it should not represent a definitive contraindication for CRS and HIPEC.

Pseudomyxoma Peritonei Arising from Urachal Mucinous Neoplasms: a Case Series and Updated Literature Review.

To report a case series of patients with pseudomyxoma peritonei (PMP) from urachal mucinous neoplasm (UMN) treated with CRS and HIPEC at a high-volume referral centre, along with an updated literature review. Retrospective review of cases treated between 2000 and 2021. A literature review using MEDLINE and Google Scholar databases was performed. Clinical presentation of PMP from UMN is heterogeneous, and common symptoms are abdominal distension, weight loss, fatigue and haematuria. At least one tumour marker among CEA, CA 19.9, and CA 125 was elevated in the six cases reported, and 5/6 had a preoperative working diagnosis of urachal mucinous neoplasm suspected on detailed cross-sectional imaging. Complete cytoreduction was achieved in five cases, while one patient underwent maximal tumour debulking. Histological findings mirrored the findings of PMP from appendiceal mucinous neoplasms (AMN). Overall survival ranged between 43 and 141 months after complete cytoreduction. On literature review, 76 cases have been reported to date. Complete cytoreduction is associated with good prognosis for patients with PMP from UMN. A definitive classification system is still not available. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-022-01694-5.

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.

Outcomes of home parenteral nutrition in 34 patients with intestinal failure from recurrent or progressive peritoneal malignancy of gastro-intestinal tract origin.

OBJECTIVES: To investigate the outcomes of 34 patients with intestinal failure secondary to advanced peritoneal malignancy on home parenteral nutrition (HPN). METHODS: A retrospective analysis of all known patients receiving HPN at any time between January 2012 and the 31st March 2020 registered in a high volume peritoneal malignancy surgical centre database. RESULTS: The median duration of HPN for all patients was 309.5 days (range 31-2198). Overall 11/34 went on to have multivisceral transplants. Of these 5/11 resumed normal oral intake off HPN, 3 died and 3 required ongoing HPN. Average time on HPN for patients with pseudomyxoma peritonei of appendix origin was 338 days (71-2198) compared with 90 days (31-260) in the group with more aggressive tumours. CONCLUSIONS: HPN is feasible and effective in selected patients with pseudomyxoma peritonei as either a bridge to transplant or definitive treatment. As expected, patients with more aggressive tumours fare worse.

Efficacy of fibrinogen concentrate in major abdominal surgery - A prospective, randomized, controlled study in cytoreductive surgery for pseudomyxoma peritonei.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei (PMP) is associated with excessive bleeding and acquired fibrinogen deficiency. Maintaining plasma fibrinogen may support hemostasis. OBJECTIVES: To compare hemostatic efficacy and safety of human fibrinogen concentrate (HFC) vs cryoprecipitate as fibrinogen sources for bleeding patients with acquired fibrinogen deficiency undergoing PMP CRS. METHODS: FORMA-05 was an off-label single-center, prospective, randomized, controlled phase 2 study. Patients undergoing PMP surgery with predicted intraoperative blood loss ≥2 L received human fibrinogen concentrate (HFC; 4 g) or cryoprecipitate (two pools of 5 units, containing approximately 4.0-4.6 g fibrinogen), repeated as needed. The primary endpoint was a composite of intraoperative and postoperative efficacy, graded using objective 4-point scales and adjudicated by an independent committee. RESULTS: One hundred percent of patients receiving HFC (95% confidence interval: 83.9-100.0, n = 21) or cryoprecipitate (84.6-100.0, n = 22) achieved hemostatic success. HFC demonstrated noninferior efficacy (P = .0095; post hoc) and arrived in the operating room 46 minutes faster. There were significantly greater mean increases with HFC vs cryoprecipitate in plasma fibrinogen (0.78 vs 0.35 g/L; P < .0001) and FIBTEM A20 (3.33 vs 0.93 mm; P = .003). Factor XIII, factor VIII, and von Willebrand factor activity were maintained throughout surgery. Only red blood cells were transfused intraoperatively (median units: HFC group, 1.0; cryoprecipitate group, 0.5). Thromboembolic events were detected with cryoprecipitate only. Safety was otherwise comparable between groups. CONCLUSIONS: Human fibrinogen concentrate was hemostatically efficacious in patients undergoing major abdominal PMP surgery, with a favorable safety profile. These results are relevant to other surgical settings where bleeding and acquired fibrinogen deficiency occur.

Do patients undergoing cytoreductive surgery and HIPEC for peritoneal malignancy need parenteral nutrition?

BACKGROUND: To analyse the duration of parenteral nutrition (PN) in patients treated for peritoneal malignancy with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) over a 2 year period at a single UK National referral centre. METHODS: A retrospective analysis of prospective data for all patients (n=321) who underwent CRS and HIPEC for peritoneal malignancy at the Peritoneal Malignancy Institute Basingstoke between April 1, 2013 and March 31, 2015.Duration of PN was compared between primary tumour site (appendix, colorectal, mesothelioma and other); completeness of CRS (complete CRS vs. major tumour debulking) and pre-operative nutritional assessment measures (including Mid Upper Arm Circumference). RESULTS: The median duration of PN was 9 days (range 2-87 days). A total of 13 % of patients had PN for less than 7 days and 6 % for 5 days or less. There was no significant difference in duration of PN between the different tumour sites. Two factors that may increase the duration of PN include having major tumour debulking (MTD) and a baseline MUAC<23.5 cm. CONCLUSIONS: Most patients who underwent CRS and HIPEC for peritoneal malignancy required PN for more than 7 days with poor pre-operative nutritional status and inability to achieve complete cytoreduction predictors of prolonged PN requirements.