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.

Risk of Ovarian Involvement in Advanced Colorectal or Appendiceal Tumors Involving the Peritoneum.

BACKGROUND: Ovarian metastases of GI tumors grow rapidly and are relatively resistant to systemic chemotherapy. They may be unilateral or bilateral and macroscopic or occult. The risk of macroscopic ovarian involvement or occult involvement of macroscopically normal ovaries is unquantified. OBJECTIVE: This study aims to quantify the risks of ovarian involvement in patients with peritoneal malignancy undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. DESIGN: This was a retrospective analysis of a dedicated prospective malignancy database. SETTINGS: This study was conducted at a high-volume tertiary referral center for peritoneal malignancy. PATIENTS: Female patients with at least 1 remaining ovary, undergoing complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal tumors or colorectal peritoneal metastases between January 2010 and March 2015 were included. OUTCOME MEASURES: Data regarding ovarian involvement was extracted from surgical and histological records. RESULTS: Two hundred fifty-eight female patients with at least 1 ovary underwent complete cytoreduction and hyperthermic intraperitoneal chemotherapy during the study period. In total, 141 of 258 (54.7%) patients had ovarian tumor involvement, and 80% with at least 1 macroscopically abnormal ovary had bilateral involvement. Of 40 patients with 1 macroscopic ovarian metastasis, microscopic involvement of the contralateral ovary was found in 18 of 40 (45.0%). Of 141 patients in whom both ovaries were macroscopically normal, 24 of 141 (17.0%) patients had microscopic ovarian involvement. LIMITATIONS: The retrospective nature limits the interpretation of these results. CONCLUSIONS: Occult malignancy was present in 17% when both ovaries looked macroscopically normal and in 45% of contralateral normal-looking ovaries if the other ovary was macroscopically involved. These results help to inform preoperative consent and intraoperative decision making in patients with advanced appendiceal and colorectal malignancy, and are of benefit in managing advanced lower GI tract malignancy.

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.

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.