Randomized Controlled Trial Investigating Perioperative Immunonutrition for Patients Undergoing Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Immunonutrition has been shown to reduce hospital stay and postoperative morbidity in patients undergoing gastrointestinal, and head and neck surgery. However, its use has not been demonstrated in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aims to determine the effectiveness of perioperative immunonutrition on patients undergoing CRS-HIPEC in reducing length of hospitalization and postoperative complications. PATIENTS AND METHODS: From April 2017 to December 2018, patients undergoing CRS-HIPEC for peritoneal metastases in a single center were enrolled in a randomized controlled trial. Patients with evidence of intestinal obstruction or with diabetes mellitus were excluded. Patients were randomly assigned in a 1:1 fashion to receive perioperative oral immunonutrition or standard nutritional feeds. Length of hospital stay and rates of wound infection and complications were recorded and compared between the two groups in an intention-to-treat manner. RESULTS: A total of 62 patients were recruited and randomized into two groups. Compliance to nutritional feeds in the preoperative period was significantly higher in the standard nutrition group (95.2% versus 75.4%, p = 0.004). There was no difference in postoperative compliance rates. Length of hospital stay and rates of wound infection and postoperative complications were higher in the standard nutrition group when compared with patients on immunonutrition (15.5 versus 11.1 days, p = 0.186; 19% versus 9.7%, p = 0.473; 16% versus 9.7%, p = 0.653; respectively). CONCLUSIONS: Patients undergoing CRS-HIPEC who received perioperative immunonutrition had shorter hospitalization and less wound infections and postoperative complications, although the differences with the standard nutrition group were not statistically significant. Potential benefits of perioperative immunonutrition need to be further evaluated in larger studies.

High intra-abdominal pressure during hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS) for peritoneal surface malignancies.

OBJECTIVE: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represent a mainstay of treatment for peritoneal malignancies. There is evidence that HIPEC using high intra-abdominal pressure (IAP) results in increased tissue penetration, although its safety profile remains relatively unknown. We thus aim to evaluate differences in intra- and post-operative outcomes in patients undergoing CRS-HIPEC with different levels of IAP. METHODS: This pilot prospective cohort study was conducted from January 2020 to February 2021 with patients undergoing CRS-HIPEC. Low IAP during HIPEC was defined as <18 mmHg and high IAP as ≥18 mmHg. Data was collected on patient and tumor characteristics, intra-operative clinical and biochemical parameters, and immediate post-operative outcomes. RESULTS: 40 patients underwent CRS-HIPEC (n low = 20, n high = 20). Median IAP in the low and high IAP groups were 12.0 and 19.0 mmHg respectively. During HIPEC, both groups experienced increase in heart rate, central venous pressure, end tidal CO2, temperature, and serum glucose, with decrease in mean arterial pressure and base excess. There were no significant differences in hemodynamics between the 2 groups. Mild electrolyte derangements and a decrease in hemoglobin were noted in the high IAP group but were of small magnitude. Post-operatively, high IAP did not result in increased rate of complications, time to full feeds, ICU or total hospital stay. CONCLUSIONS: High IAP in HIPEC is well tolerated and did not result in additional adverse events.

Predicting Early and Late Readmissions Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Postoperative readmissions not only burden the healthcare system but may also affect clinical outcomes of cancer patients. Despite this, little is known about readmissions after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), or their impact on survival outcomes. PATIENTS AND METHODS: A single-institution retrospective cohort study of CRS-HIPEC procedures from April 2001 and September 2019 was performed. Early readmission (ERA) was defined as hospitalization within 30 days of discharge post-CRS/HIPEC, while late readmission (LRA) was defined as hospitalization between day 31 and 90 after discharge. Patient demographic, oncological, and perioperative factors were analyzed to identify predictors of readmission, and comparison of survival outcomes was performed. RESULTS: Overall, 342 patients who underwent CRS-HIPEC were included in the study. The incidence of ERA and LRA was 18.5% and 7.4%, respectively. High-grade postoperative complication was the only independent predictor of ERA (HR 3.64, 95% CI 1.47-9.02), while comorbid hypertension (HR 2.71, 95% CI 1.17-6.28) and stoma creation (HR 2.83, 95% CI 1.23-6.50) were independent predictors for LRA. Patients with readmission had significantly worse disease-free survival than patients who had no readmission (NRA) (LRA 1.1 years, ERA 1.2 years, NRA 1.8 years, p = 0.002), and patients with LRA had worse median overall survival (2.1 years) than ERA patients (3.3 years) or patients without readmission (4.4 years) (p < 0.001). CONCLUSIONS: Readmission following CRS-HIPEC is associated with adverse survival outcomes. In particular, LRA may portend worse prognosis than ERA.

Postoperative Inflammatory Marker Surveillance in Colorectal Peritoneal Carcinomatosis.

BACKGROUND: The prognostic significance of inflammatory markers in solid cancers is well-established, albeit with considerable heterogeneity. This study sought to investigate the postoperative inflammatory marker trend in peritoneal carcinomatosis (PC), with a focus on colorectal PC (CPC), and to propose optimal surveillance periods and cutoffs. METHODS: Data were collected from a prospectively maintained database of PC patients treated at the authors' institution from April 2001 to March 2019. The platelet-lymphocyte ratio (PLR), the neutrophil-lymphocyte ratio (NLR), and the lymphocyte-monocyte ratio (LMR) were collected preoperatively and on postoperative days 0, 1 to 3, 4 to 7, 8 to 21, 22 to 56, and 57 to 90 as averages. Optimal surveillance periods and cutoffs for each marker were determined by maximally selected rank statistics. The Kaplan-Meier method and Cox proportional hazard regression models were used to investigate the association of inflammatory markers with 1-year overall survival (OS) and recurrence-free survival (RFS) using clinicopathologic parameters. RESULTS: The postoperative inflammatory marker trend and levels did not differ between the patients with and those without hyperthermic intraperitoneal chemotherapy (HIPEC). Low postoperative LMR (days 4-7), high postoperative NLR (days 8-21), and high postoperative PLR (days 22-56) were optimal for prognosticating poor 1-year OS, whereas high postoperative PLR and NLR (days 57-90) and low postoperative LMR (days 8-21) were associated with poor 1-year RFS. A composite score of these three markers was prognostic for OS in CPC. CONCLUSIONS: The reported cutoffs should be validated in a larger population of CPC patients. Future studies should account for the inflammatory response profile when selecting appropriate surveillance periods.

Neoadjuvant tyrosine kinase inhibitors in rectal gastrointestinal stromal tumours: a provision for enhanced oncological and functional outcomes.

BACKGROUND: The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs. METHODS: A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared. RESULTS: Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1-3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group. CONCLUSIONS: Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.

Retrospective quality of life study in patients with retroperitoneal sarcoma in an Asian population.

BACKGROUND: Retroperitoneal sarcoma represents 15% of sarcomas. The mainstay of treatment is surgery where a majority of patients require multi-visceral resections that may significantly impact their quality of life (QOL) following surgery. Studies in other cancers have shown that QOL may not be significantly impacted after radical or extensive surgery. However, there are limited studies examining the QOL specifically in patients with retroperitoneal sarcoma. In this pilot study, we retrospectively evaluated the QOL of patients with retroperitoneal sarcoma. METHODS: 32 out of 90 patients who underwent surgical intervention for retroperitoneal sarcoma in National Cancer Centre Singapore from January 1999 to August 2018 who were alive and on follow-up were included in this study. EORTC-QLQ-C30 was administered to the patients. RESULTS: The median age of our patients was 59 years (range, 35-84), and median time from surgery to the implementation of questionnaire was 2.5 years (range, 0.05-9.6). Younger patients had significantly better differences in global health, physical and role functioning scores as compared to older individuals. Female patients reported higher global health, physical, emotional and social functioning scores than males. Patients who were more than 2 years post-surgery exhibited better QOL scores as compared to those who had more recent surgery. Our patients had comparable global health and functioning scores compared to a reference group of outpatient cancer patients at our institution. CONCLUSIONS: Our pilot study investigating the QOL of patients with retroperitoneal sarcoma has shown that patients need to be followed up for at least 2 years following surgery to evaluate their QOL. In general, they achieved better functioning scores when compared with other cancer patients. These findings support the need for larger-scale prospective studies to further evaluate the QOL of these patients.

High-grade complication is associated with poor overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly used in peritoneal carcinomatosis (PC) management. This modality is criticized for its high morbidity and mortality. We evaluate the morbidity and mortality of patients undergoing this procedure in our institution. METHODS: A review of our institution's database was performed. All patients who underwent CRS/HIPEC between July 2011 and March 2018 were divided into three groups: no, low-grade, and high-grade complications. Prognostic factors were determined with Cox regression, while morbidity risk factors were analyzed using multinomial logistic regression. RESULTS: 225 consecutive patients underwent CRS/HIPEC. The most common primary cancer types were colorectal (35.1%), appendiceal (25.8%), and ovarian (22.2%). Median age was 55 years old (range 14-77), and patients were typically female (68.0%). 38.7% developed low-grade complications and 14.7% had high-grade complications. No 30-day mortality was observed. Different tumor origins are associated with significant differences in overall survival (p < 0.001). Patients without complications had significantly better survival than those with high-grade complications (HR 0.35, 95% CI 0.15-0.81, p < 0.001). Males were more likely to develop low-grade complications (OR 3.30, 95% CI 1.31-8.30, p = 0.011). Intra-operative blood loss was associated with greater odds of developing any post-operative complications (OR 1.001, 95% CI 1.0003-1.002, p = 0.007; and OR 1.002, 95% CI 1.001-1.002, p < 0.001, for low and high grade, respectively). CONCLUSION: Presence of high-grade complication was associated with poorer survival in patients after CRS/HIPEC. Pre-operative careful assessment of patients is pivotal to ensure favorable patient outcome following this complex procedure.

The importance of synchronicity in the management of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Colorectal peritoneal metastases (CPM) occur in up to 13% of patients with colorectal cancer, presenting either synchronously or metachronously. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) have been increasingly utilised for selected CPM patients with favourable outcomes, though its benefits may differ for synchronous (s-CPM) and metachronous CPM (m-CPM). METHODS: A retrospective analysis of CPM patients treated with CRS and HIPEC at the National Cancer Centre Singapore over 15 years was performed. In the s-CPM group, CPM was diagnosed at primary presentation with CRS and HIPEC performed at the time of or within 6 months from primary surgery. In the m-CPM group, patients developed CPM > 6 months after primary curative surgery. RESULTS: One hundred two patients with CPM were treated with CRS and HIPEC. Twenty (19.6%) patients had s-CPM and 82 (80.4%) had m-CPM. Recurrences occurred in 45% of s-CPM and in 54% of m-CPM (p = 0.619). Median overall survival was significantly prolonged in patients with m-CPM (45.2 versus 26.9 months, p = 0.025). In a subset of m-CPM patients with limited PCI in whom ICU stay was not required, a survival advantage was seen (p = 0.031). CONCLUSION: A survival advantage was seen a subset of m-CPM patients, possibly representing differences in disease biology.

Are positron emission tomography-computed tomography (PET-CT) scans useful in preoperative assessment of patients with peritoneal disease before cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)?

INTRODUCTION: CRS and HIPEC confer survival benefit in selected patients with peritoneal metatases (PM). Accurate preoperative assessment of disease burden and exclusion of distant metastases are crucial in selecting the appropriate patient. We evaluate the utility of PET-CT scans in comparison with CT and MRI scans in patients considered for CRS and HIPEC. METHODS: Data were retrospectively collected from patients who had been discussed for CRS and HIPEC between January 2011 and December 2015, at our institutional multidisciplinary tumour board. Patients who underwent PET-CT scan were included. Results of PET-CT were compared against traditional imaging. Patient and tumour factors were analysed to identify those who were most likely to benefit from PET imaging. RESULTS: Four hundred and seven patients were considered for CRS and HIPEC. PET-CT was performed for 128(31.4%) patients: being the only imaging modality in 37 and used as an adjunct in 91. In the latter group, it was not beneficial in 58 patients as it provided no additional information (n = 33) or showed lesions of minimal FDG uptake (n = 25). In 33 patients, PET-CT provided definitive answers for indeterminate lesions seen on CT and MRI, confirmed the diagnosis of peritoneal disease in 10 patients (30.3%), identified extra-peritoneal disease and/or nodal metastases in 15 (45.5%) and excluded peritoneal disease in 8 (24.2%). The usefulness of PET-CT was predicted by tumour histology (p = .009), with non-mucinous tumours benefitting the most. CONCLUSION: Our results suggest that PET-CT can be used as an adjunct to CT and/or MRI scans, when lesions on the CT/MRI scans are indeterminate, and that it is most useful in patients with non-mucinous tumours.

Exploring the trend in referrals for consideration of CRS and HIPEC to understand the attitudes of clinicians in the development of a national cancer centre programme in peritoneal disease.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival in selected patients with peritoneal metastases. However, only some patients who are potentially eligible for the procedure are considered and referred to the appropriate surgical department. By studying the trends of patients being considered for CRS and HIPEC in our centre, we hope to better understand the demographics of our patient cohort and the attitudes of physicians involved towards CRS and HIPEC. METHODS: Patients who were presented and discussed at our institution's multidisciplinary tumour board (MDTB) for consideration of CRS and HIPEC, between 5 January 2011 and 16 December 2015, were identified from the institutional database and included in the study. Patient demographics and clinico-pathological data were retrospectively collected from electronic records and clinical charts. RESULTS: A total of 407 patients were presented at the MDTB for consideration of CRS and HIPEC. Referrals were most commonly from oncology-related departments (65.8%, n = 268). This was followed by referrals from other hospitals (15.0%, n = 61), overseas self-referrals (12.0%, n = 49) and non-oncologic departments within the same institution (7.1%, n = 29). Referrals made by oncology-related departments and overseas self-referrals showed an increasing trend over the years. Of the patients discussed, 197 patients (48.4%) were recommended for CRS and HIPEC, and 134 (68.0%) successfully underwent the procedure. CONCLUSIONS: There is growing acceptance of CRS and HIPEC in patients and oncologic-related departments. However, consideration of this procedure as a treatment option remains low in non-oncologic departments. Dissemination of information and well-defined clinical recommendations may help physicians identify and select potentially eligible patients for consideration of CRS and HIPEC.

Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC. METHODS: Retrospective analysis of a prospectively collected database of CRS-HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared. RESULTS: Out of 214 CRS-HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I-II), and 49 patients (23%) suffered high-grade complications (grade III-V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens. CONCLUSIONS: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.

CA-125: an inaccurate surveillance tool immediately after cytoreductive surgery and hyperthermic intraoperative chemotherapy (CRS-HIPEC)?

OBJECTIVE: This study seeks to evaluate pre and post-operative CA-125 in patients undergoing complete cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and understand the time frame before values normalise allowing use as a surveillance tool to resume. METHODS: A retrospective review was carried out of 94 patients undergoing CRS-HIPEC to compare pre-operative CA-125 values, measured within one week prior to surgery to post-operative readings within the first 30 d. Raised CA-125 was defined using as a value >35 U/ml. RESULTS: Of 63 (67%) patients with normal pre-operative CA-125, 22 (35%) had raised post-operative CA-125, and consisted of patients with colorectal (n = 8), appendiceal (n = 6), ovarian (n = 4) or other (n = 4) cancers. The average peak CA-125 was 80 U/ml occurring on median 10th post-operative day (POD) (range 7-30). The median day of normalisation for patients with normal pre-operative and raised post-operative CA-125 was 57 (range 28-115). The median day of normalisation for patients with raised pre-operative CA-125 was POD 41 (range 1-114). Notably 10 patients had initial normalisation (median POD 1, range 1-6), followed by subsequent raised value (median POD 10, range 5-40) and re-normalisation (median POD 47, range 19-104). DISCUSSION: For patients with raised pre-operative CA-125 an immediate post-operative CA-125 within 3 d may be useful to assess normalisation following surgery. Aside from immediate measurement CA-125 is misleading and should not be measured post-operatively within the first 3 months after surgery following which its use as a surveillance marker can resume.

Does having a gastrectomy delay time to feeding and prolong hospital stay in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?

AIM: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used to treat selected patients with peritoneal carcinomatosis, but can be associated with prolonged hospital stay, significant morbidity and mortality. Our objective was to assess whether patients undergoing gastrectomy as part of CRS/HIPEC were at increased risk of delayed feeding time and prolonged hospital stay. METHODS: Two hundred and fourteen consecutive patients with peritoneal carcinomatosis treated with CRS/HIPEC between 2001 and 2016 were stratified by whether CRS included gastrectomy (n = 19, 9%) and compared. Primary outcomes were time to full feeds and rate of serious morbidity (Clavien-Dindo grades III-V). Secondary outcomes were durations of ICU and hospital stays. RESULTS: Of 214 patients undergoing CRS/HIPEC, those undergoing gastrectomy (19, 8.9%) had increased time to full feeds (8 vs. 5 days, p < 0.01), and duration of ICU (2 vs. 1 days, p < 0.01) and total hospital stays (16 vs. 14 days, p = 0.013). There was no significant increase in serious complications, although increased risk of pneumonia was noted (21% vs. 4.1%, p = 0.011). Undergoing gastrectomy was not independently prognostic in multivariable analysis including high peritoneal tumour load (PCI >12), multiple CRS procedures (number >2) and operation duration (>480 min) in which operative duration remained independently prognostic (p < 0.01). CONCLUSIONS: After surgery, early oral refeeding may be beneficial in the majority of patients undergoing CRS/HIPEC. However, patients found to have high peritoneal tumour load with extended surgery and those who underwent gastrectomy should be considered for early post-operative TPN due to the significant risk of delayed time to full feeds.

Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are used in the management of selected peritoneal malignancies. While most patients achieve long-term disease-free survival, there remains a group with early recurrence (ER). We aim to investigate the clinical factors associated with ER. METHODS: A retrospective review of a prospectively maintained database of CRS-HIPEC patients treated between April 2001 and Feb 2016 was performed. ER was defined as recurrence within 12 months of CRS-HIPEC. Patients were stratified according to time to recurrence and only patients with at least 12-month follow-up were included. Perioperative factors were investigated, and subgroup analyses of colorectal, ovarian and appendiceal groups were performed. RESULTS: Of the 144 patients included, 30.6% were colorectal, 36.8% ovarian and primary peritoneal, 24.3% appendiceal, 2.1% mesothelioma and 6.3% were of other origins. Thirty-nine patients (27%) suffered ER. Univariable and multivariable analyses revealed that primary tumour type (p = 0.02) and post-CRS adjuvant treatment (p = 0.04) were associated with ER. Appendiceal patients had a lower odds of ER compared to colorectal patients [OR = 0.15 (0.043-0.502) p < 0.002]. Patients who received post-CRS adjuvant treatment had a lower odds of ER than patients without adjuvant treatment [OR = 0.32; (0.128-0.818) p = 0.02]. CONCLUSION: There remains a 27% risk of ER after CRS-HIPEC. Better patient selection and the administration of adjuvant chemotherapy may help to reduce ER.

Acute kidney injury in ovarian cancer patients undergoing cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS-HIPEC) prolongs survival in patients with metastatic peritoneal disease. We look at the incidence of acute kidney injury (AKI) in patients who have received cisplatin during CRS-HIPEC in the treatment of peritoneal carcinomatosis from an ovarian primary, and identify possible peri-operative risk factors. METHODS: Between 2005 and 2013, we performed CRS-HIPEC on 47 patients with ovarian primaries and peritoneal metastasis. Retrospective data were collected on the patient's demographics, treatment details and outcomes. Renal impairment was graded according to the NCI-CTCAE 3.0 criteria. RESULTS: There were 47 patients, with a median age of 50 (24-74) years. The median baseline creatinine was 53 µmol/L (23-102) and median baseline albumin of 39 g/L (13-45). All underwent pre-operative chemotherapy for a median of six cycles (0-22) with a median of 15 days between chemotherapy and surgery. They received intra-operative cisplatin at a temperature of 40 °C for 60 min at a median dose of 90 mg/kg. 19 (40.4%) experienced post-operative AKI, of which 5 (8.5%) developed grade 3 and 4 impairment. Two (4.3%) required long-term dialysis. Univariate analysis showed that risk factors for AKI included age, baseline creatinine, baseline estimated glomerular filtration rate, pre-operative albumin, number of cycles of pre-operative carboplatin, time interval between pre-operative chemotherapy and CRS-HIPEC and volume of blood transfusions. CONCLUSIONS: Identification of risk factors for AKI post-CRS-HIPEC helps improve pre-operative patient selection and optimisation, facilitate tailoring of chemotherapy, and foster closer peri-operative monitoring and fluid management in at-risk patients.

Prospective Quality of Life Study for Colorectal Cancer Patients with Peritoneal Carcinomatosis Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is becoming accepted treatment for peritoneal carcinomatosis (PC) from colorectal cancer. Quality of life (QoL) for patients after surgery is still a concern amongst physicians despite studies that show that QoL recovers after surgery. We conducted a prospective QoL study on patients undergoing CRS and HIPEC and attempt to identify factors that affect the QoL. METHODS: Patients who underwent CRS and HIPEC for PC from colorectal cancer from March 2012 to January 2015 were included. The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and the colorectal module (QLQ-CR29) were administered prior to surgery and thereafter at 3, 6, and 12 months. RESULTS: Twenty-three patients underwent 25 procedures. Median disease-free survival was 12.9 months [95 % confidence interval (CI) 2.5-19.3]. Physical and role functioning scores decreased at 3 months but returned to baseline at 6 months. There were significant increases in emotional and social functioning scores at 6-12 months and improvements in all symptoms scales at 6-12 months, especially the fatigue and appetite scores. A higher PCI score, longer duration of surgery, the presence of a stoma, and recurrence within 3 months were associated with a poorer QoL. CONCLUSIONS: QoL after CRS and HIPEC improved or returned to baseline in all categories by 6-12 months after surgery. Patient selection is important not only for improved survival but also for improved QoL.

Does early post-operative intraperitoneal chemotherapy (EPIC) for patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) make a difference?

INTRODUCTION: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early post-operative intraperitoneal chemotherapy (EPIC). We compared the morbidities, overall survival (OS) and disease free survival (DFS) between two groups of patients who underwent CRS and HIPEC alone and with EPIC at our institution. METHODS: A retrospective review of 111 patients with PC who were treated with CRS + HIPEC or CRS + HIPEC + EPIC in a single institution between January 2008 and April 2014 was performed. EPIC with 5-fluorouracil or paclitaxel was utilised, depending on the primary tumour. RESULTS: Patients who received EPIC had a higher proportion of grade III and above post- operative complications (58% versus 25%; p = 0.048) and a longer duration of hospitalisation (16 days versus 13 days; p = 0.019) than patients without EPIC. There were no significant OS and DFS differences between the EPIC and no EPIC groups (log-rank p = 0.231 and p = 0.144, respectively). CONCLUSION: The use of EPIC after CRS + HIPEC for PC potentially results in increased morbidity and longer hospitalisation, and is unlikely to affect survival outcomes. Based on our experience, EPIC is not recommended after CRS and HIPEC.

Intraperitoneal Vascular Endothelial Growth Factor: A Prognostic Factor and the Potential for Intraperitoneal Bevacizumab Use in Peritoneal Surface Malignancies.

INTRODUCTION: Intraperitoneal (IP) vascular endothelial growth factor (VEGF) levels have been shown to vary in the peritoneal cavity of patients with peritoneal surface malignancies. Our purpose was to correlate levels of IP VEGF with overall and disease-free survival to identify whether IP VEGF can be used to prognosticate patients and the possible role of IP bevacizumab. METHODS: From February to October 2012, 97 consecutive patients with peritoneal carcinomatosis were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Intravenous (IV) VEGF levels were taken before surgery, whereas IP VEGF levels were taken at various time points during and after surgery. RESULTS: Median follow-up was 19.48 months. On univariate analysis, a lower IP VEGF taken just after incision (T1) was associated with improved overall (P = 0.0004) and disease-free survival (P = 0.0006) at 2 years. A lower T1/IV VEGF ratio also was associated with improved overall (P = 0.004) and disease-free survival (P = 0.0051). On multivariate analysis, a lower T1 was associated with improved overall survival, whereas a lower T1/IV VEGF was associated with improved disease-free survival. On subset analysis, these two variables were associated with improved survival in colorectal cancers. CONCLUSIONS: A lower IP VEGF level prior to surgery is associated with improved survival. The use of preoperative intraperitoneal bevacizumab for patients with a heavy disease load should be considered, especially in colorectal cancers.