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

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

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.

Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases.

BACKGROUND AND OBJECTIVES: To review long-term survival outcomes of patients with Peritoneal metastasis (PM) who underwent colorectal cancer (CRS) and intraperitoneal chemotherapy (PIC). METHODS: Patients that underwent CRS, with or without PIC, from January 1996 to March 2018 at the Peritonectomy Unit of St. George Hospital, Sydney were retrospectively analyzed from a prospectively maintained database. RESULTS: The study comprised of 1225 cases, including 687 females (56.1%) and 538 males (43.9%). Diagnoses included CRC (n = 363), followed by HAMN (n = 317), LAMN (n = 297), mesothelioma (n = 101), ovarian cancer (n = 55), and others including gastric, sarcoma, and neuroendocrine tumor (n = 92). The median OS, 5- and 10-year survivals for CRC were 35 months, 33% and 8%, respectively. Patients with LAMN, in relative to HAMN, experienced a higher median OS, 5- and 10-year survivals (248 months vs 63 months; 82% vs 52% and 59% vs 28%). The median OS for mesothelioma was 60 months with 5- and 10-year survivals of 48% and 19%, respectively. In ovarian cancer, the median OS was 30 months with 5- and 10-year survivals of 26% and 10%, respectively. For the remaining histological diagnoses, median OS and 5-year survival were 28 months and 27%, respectively. CONCLUSION: Our large-cohort data showed that CRS/PIC can provide long-term survival benefit to patients with PM of gastrointestinal and ovarian origin.

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.

Survival difference between mucinous vs. non-mucinous colorectal cancer following cytoreductive surgery and intraperitoneal chemotherapy.

BACKGROUND: It is believed that the oncologic behavior of mucinous colorectal adenocarcinoma (MC) is different from non-mucinous adenocarcinoma (NMC). The aim of the study is to compare long-term survivals between patients with MC and those with NMC following cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). METHODS: This was a retrospective study of prospectively collected data of patients with peritoneal metastases of colorectal origin following CRS and IPC. Group I included patients with MC which was defined as being composed of >50% extracellular mucin. Group II included those with NMC. Subgroup analysis was performed according to the location of primary tumor. RESULTS: A total of 213 patients were included in this study. The two groups had similar hospital mortality, high dependency unit stay. MC group had a significantly longer mean intensive care unit (ICU) stay (p = .037) and total hospital stay (p = .037). There was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups (p = .657 and p = .938, respectively). Multivariate analysis showed that the presence of mucin was not an independent negative prognostic factor for OS (p = .190). CONCLUSION: In summary, patients with MC had a similar long-term survival outcome with those with NMC following CRS and IPC.

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

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

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

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

Gastric perforation following cytoreductive surgery and perioperative intraperitoneal chemotherapy: a case series of six.

BACKGROUND: Incidence of gastric perforation following cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) is not widely reported. METHODS: Suitable patients were identified from our database of 1028 procedures. Relevant information was then gathered via medical records and operation reports for these patients. RESULTS: Six patients suffered early postoperative gastric perforation following the procedure (0.58%), all of whom received heated intraoperative intraperitoneal chemotherapy (HIPEC). Surgical exploration revealed protrusion of nasogastric (NG) tube through stomach wall defects which were either located at or near the greater curvature of stomach. These patients were managed successfully with operation, and no mortality was recorded. CONCLUSIONS: Gastric perforation following CRS and PIC is most likely the result of a multifactorial process. To reduce the risk of such complication, avoiding nasogastric suction in these patients may prove helpful. Any suspected perforated viscus must be addressed promptly to avoid unwanted morbidity and mortality from the procedure. To our knowledge, conservative management has not been documented to work in this subgroup and surgery remains the mainstay of treatment.

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

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

Effects of sex hormones on survival of peritoneal mesothelioma.

BACKGROUND: Previous studies have suggested the presence of steroid receptors as a favourable prognostic factor in peritoneal mesothelioma (PM). This study aims to investigate possible hormonal effects on survival of PM. METHODS: This is a retrospective study of prospectively collected data of 52 consecutive patients with PM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by the same surgical team at St George Hospital in Sydney, Australia, between April 1996 and April 2013. Females were arbitrarily divided into assumed premenopausal (< 51 years old; n = 15) and assumed postmenopausal (≥ 51 years old, n = 9). In each gender group, patients were furthered divided into three age groups (< 40, 40-60, > 60). A significant statistical difference was defined as p < 0.05. RESULTS: Females with epithelial mesothelioma had a significantly higher survival than males (p = 0.023). They also had a better overall median survival (> 60 months) than males (43 months), although this difference was not statistically significant (p = 0.098). Survival of postmenopausal females became similar to males after excluding benign cystic mesothelioma. CONCLUSIONS: The better survival in premenopausal females could probably be explained by higher levels of oestradiol and progesterone. Also, our data suggests that higher rates of benign cystic mesothelioma in females was not the key reason for the better survival in female patients, further supporting the hypothesis of hormonal links with survival of PM. Therapeutic effects of sex steroid hormones on PM may be a valuable area to explore.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis in the elderly.

BACKGROUND: Peritoneal carcinomatosis is life-threatening without cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Only a few studies in the literature addressed the relationship between age and outcomes of peritonectomy. This study was designed to review the clinical outcomes in elderly patients who underwent CRS and PIC. METHODS: This is a retrospective study of prospectively collected data of 611 consecutive patients with peritoneal carcinomatosis who underwent CRS and PIC by the same surgical team at St George Hospital in Sydney, Australia, between January 1996 and December 2013. Patients were divided into two groups; group 1 (<65 years old, n = 487) and group 2 (≥ 65 years old, n = 124). Subgroup analysis was performed in patients who were ≥75 years old (n = 20). A significant difference was defined as p < 0.05. RESULTS: There was no significant statistical difference in terms of mean total hospital stay, intensive care unit stay, high dependency unit stay and complication rates. Postoperative mortality was 2 and 3 % in groups 1 and 2, respectively. Overall survival did not reach a statistical significance between the two groups. In subgroup analysis, patients showed similar morbidity results to patients who were <65 years old. CONCLUSIONS: CRS and PIC can be safely done in the elderly. Age alone should not be the single exclusion criterion but rather taken into consideration along with other factors to determine the suitability of elderly patients.

Systematic review of efficacy and outcomes of salvage liver transplantation after primary hepatic resection for hepatocellular carcinoma.

BACKGROUND AND AIM: Upfront liver transplantation is the gold standard in the treatment of patients with hepatocellular carcinoma (HCC) and cirrhosis, but a shortage of donor organs negatively impacts on survival outcomes, with significant disease progression during long waiting lists. This systematic review evaluates the safety and efficacy of salvage liver transplantation (SLT) as treatment for recurrent HCC after initial hepatic resection. METHODS: Electronic searches of Pubmed, Embase, and Medline databases identified 130 abstracts, from which 16 eligible studies comprising 319 patients were selected for review. Studies adopting SLT following primary hepatic resection for recurrent HCC with more than five patients were included. Demographic details, morbidity and mortality indices, and survival outcomes were collected from each study and were tabulated. RESULTS: All patients included in the studies had liver cirrhosis, with the majority being Child-Pugh A (50%) and B (33%). The etiology of liver disease was hepatitis B in the majority of patients (84%). Disease recurrence occurred in 27-80% of patients at a median of 21.4 months (range 14.5-34) following initial resection. SLTs were performed on 41% of recurrences, and were associated with biliary complications (8%), infection (11%), bleeding (8%), and vascular complications (7%). There were 18 perioperative deaths (5.6%). The median 1-, 3-, and 5-year overall and disease-free survival was 89%, 80%, and 62%, and 86%, 68%, and 67%, respectively. CONCLUSION: Synthesis of available observational studies suggests that SLT following primary hepatic resection is a highly applicable strategy with long-term survival outcomes that are comparable to upfront liver transplantation.

Hyperthermic intraperitoneal chemotherapy in colorectal cancer.

BACKGROUND: This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients. PATIENTS AND METHODS: Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received-oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose-response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed. RESULTS: Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P < 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P < 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period. CONCLUSIONS: Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose-response between low- and high-dose HIPEC was reported.

Perioperative chemotherapy in colorectal cancer with peritoneal metastases: A global propensity score matched study.

Background: There is a paucity of studies evaluating perioperative systemic chemotherapy in conjunction with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal cancer peritoneal metastases (CRCPM). The aim was to evaluate neoadjuvant and/or adjuvant systemic therapy in CRCPM. Methods: Patients with CRCPM from 39 treatment centres globally from January 1, 1991, to December 31, 2018, who underwent CRS+HIPEC were identified and stratified according to neoadjuvant/adjuvant use. Crude data analysis, propensity score matching (PSM) and Cox-proportional hazard modelling was performed. Findings: Of 2093 patients, 1613 were included in neoadjuvant crude evaluation with 708 in the PSM cohort (354 patients/arm). In the adjuvant evaluation, 1176 patients were included in the crude cohort with 778 in the PSM cohort (389 patients/arm). The median overall survival (OS) in the PSM cohort receiving no neoadjuvant vs neoadjuvant therapy was 37.0 months (95% CI: 32.6-42.7) vs 34.7 months (95% CI: 31.2-38.8, HR 1.08 95% CI: 0.88-1.32, p = 0.46). The median OS in the PSM cohort receiving no adjuvant therapy vs adjuvant therapy was 37.0 months (95% CI: 32.9-41.8) vs 45.7 months (95% CI: 38.8-56.2, HR 0.79 95% CI: 0.64-0.97, p = 0.022). Recurrence-free survival did not differ in the neoadjuvant evaluation but differed in the adjuvant evaluation - HR 1.04 (95% CI: 0.87-1.25, p = 0.66) and 0.83 (95% CI: 0.70-0.98, p = 0.03), respectively. Multivariable Cox-proportional hazard modelling in the crude cohorts showed hazard ratio 1.08 (95% CI: 0.92-1.26, p = 0.37) for administering neoadjuvant therapy and 0.86 (95% CI: 0.72-1.03, p = 0.095) for administering adjuvant therapy. Interpretation: Neoadjuvant therapy did not confer a benefit to patients undergoing CRS+HIPEC for CRCPM, whereas adjuvant therapy was associated with a benefit in this retrospective setting. Funding: None.

Myxoid pleomorphic liposarcoma of the falciform ligament: a rare case report.

Liposarcomas are a group of malignancies that mainly affect adults. Myxoid pleomorphic liposarcoma (MPL) is a newly added subtype of liposarcomas [1]. It is extremely rare and mostly affects infants and children, and it has a predilection for the mediastinum. We report a case of a 58-years-old female with MPL originating from the falciform ligament who presented initially with vague abdominal pain. MPLs have an aggressive pathology and high metastasis and recurrence potential.

Sodium thiosulfate during cisplatin-based hyperthermic intraperitoneal chemotherapy is associated with transient hypernatraemia without clinical sequelae.

Objectives: Cisplatin is commonly used during intraperitoneal chemotherapy however has well-established nephrotoxic side-effects. Sodium thiosulfate is often added to cisplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) protocols to mitigate this, however evidence regarding risk of hypernatraemia is scarce as of yet. Methods: We retrospectively identified patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies of any origin at a single high-volume unit between April 2018 and December 2020. Patients were included if they received cisplatin-based HIPEC with intravenous sodium thiosulfate. Blood tests were collected pre-surgery and then daily during admission. Hypernatraemia was defined as serum sodium >145 mmol/L. Renal impairment was defined using the RIFLE criteria. Results: Eleven CRSs met inclusion criteria, the majority of which were indicated for ovarian cancer (72.7%). One (9.1%) patient with mesothelioma received mitomycin C as an additional chemotherapy agent. The incidence of hypernatraemia was 100% but all cases were transient, with no clinical sequelae observed. The rate of AKI was 36.4%, with three (27.3%) patients classified as risk and one (9.1%) instance of failure. No long-term renal impairment was observed. Conclusions: Despite biochemical evidence of mild hypernatraemia but with the absence of clinical sequelae, sodium thiosulfate appears to be safe when used in adjunct to cisplatin-based HIPEC during CRS. These findings should be evaluated with further comparative studies. When describing renal impairment, it is important that standardisation in reporting occurs, with the RIFLE and Acute Kidney Injury Network criteria now the preferred consensus definitions.

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

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

Acute Kidney Injury Following Hyperthermic Intraperitoneal Chemotherapy With Cisplatin.

BACKGROUND/AIM: Cisplatin increases the risk of acute kidney injury (AKI) during systemic chemotherapy. However, little is known about its risk of inducing AKI when used during intraperitoneal chemotherapy. This study aimed to determine the incidence of AKI in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with cisplatin. PATIENTS AND METHODS: A retrospective analysis of patients who received cisplatin-based HIPEC from November 2008 to March 2018 was undertaken to determine the incidence of AKI. RESULTS: A total of 111 patients were identified. The incidence of AKI was 15.3% (17/111). Univariate analysis showed increased peritoneal cancer index (PCI), low intraoperative and post-operative urine output were significantly associated with the development of AKI. Multivariate analyses did not identify any significant predictors factors for AKI. CONCLUSION: Cisplatin-based HIPEC is associated with AKI. At our centre, the incidence of AKI was 15.3%. Risk factors that may influence its development include high PCI and low perioperative diuresis.

Impact of signet ring cells on overall survival in peritoneal disseminated appendix cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

INTRODUCTION: To determine the effect of signet ring cell (SRC) histopathology in appendix cancer with peritoneal dissemination on overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC). MATERIALS AND METHODS: Retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for appendix cancer from April 1999 to December 2019. RESULTS: 255 patients were identified. 174 had high-grade disease with no SRC component, 35 with a low count of SRC and 46 with a high count of SRC. Median OS without SRC was 93.8 months vs 58.2 months for low count SRC and 23.7 months for high count SRC (P < 0.001). 5-year OS was 60% for patients with no SRC, 35.5% and 10% in those with low count and high count SRC respectively. On multivariate analysis, presence of SRC and complete cytoreduction score were identified as independent factors that affect OS. CONCLUSION: The presence of SRC in appendix cancer with peritoneal dissemination is associated with worse OS when compared to an absence of SRC in patients undergoing CRS/HIPEC.

Case report: Intraoperative thrombosis cardiac arrest in extended right hepatectomy involving use of local haemostatic agent in intraoperative cell salvage (ICS) and administration of recombinant activated factor VII (rFVIIa).

INTRODUCTION: In modern surgical era, local haemostatic agents and blood components such as recombinant activated factor VII (rFVIIa) have expanded surgeons' armamentarium in controlling "surgical" and "nonsurgical bleeding". We report a case of intraoperative thrombosis and cardiac arrest involving use of local haemostatic agent in intraoperative cell salvage and rFVIIa administration in extended right hepatectomy. PRESENTATION OF CASE: A 46-year-old lady underwent extended right hepatectomy using cardiopulmonary bypass (CPB) and autotransfusion with ICS for metastatic gastrointestinal stromal tumour. She became extremely coagulopathic following weaning of CPB despite an array of fluid and blood products replacements. Decision to administer rFVIIa as a measure to arrest bleeding was unsuccessful. Extensive systemic thrombosis occurred which resulted in cardiac arrest and mortality. DISCUSSION: The thromboembolic event was unclear but likely multifactorial. Two important hypotheses were the administration of rFVIIa and use of local haemostatic agent in ICS. CONCLUSION: Reported incidence of thromboembolism with use of rFVIIa in refractory bleeding is variable. More randomised controlled trials are needed to ascertain the efficacy and safety profile of the haemostatic agent. At present, off-label use of rFVIIa should be guided by the risk:benefit profile on a case-to-case basis. The authors also feel strongly against the use of local haemostatic gel in conjunction with ICS due to potential systemic circulation of the thrombin.