Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre.

BACKGROUND: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. METHODS: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. RESULTS: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. CONCLUSION: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results.

Vinorelbine Improves the Efficacy of Sorafenib against Hepatocellular Carcinoma: A Promising Therapeutic Approach.

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Despite the widespread adoption of sorafenib as the standard HCC treatment, its efficacy is constrained, frequently encountering resistance. To augment the effectiveness of sorafenib, this study investigated the synergy of sorafenib and vinorelbine using 22 HCC patient-derived xenograft (PDX) models. In this study, mice bearing HCC tumors were treated with the vehicle, sorafenib (15 mg/kg), vinorelbine (3 mg/kg), and sorafenib-vinorelbine combination (Sora/Vino). Rigorous monitoring of the tumor growth and side effects coupled with comprehensive histological and molecular analyses was conducted. The overall survival (OS) of mice bearing HCC orthotopic tumors was also assessed. Our data showed a notable 86.4% response rate to Sora/Vino, surpassing rates of 31.8% for sorafenib and 9.1% for vinorelbine monotherapies. Sora/Vino significantly inhibited tumor growth, prolonged OS of mice bearing HCC orthotopic tumors (p < 0.01), attenuated tumor cell proliferation and angiogenesis, and enhanced necrosis and apoptosis. The combination therapy effectively suppressed the focal adhesion kinase (FAK) pathway, which is a pivotal player in cell proliferation, tumor angiogenesis, survival, and metastasis. The noteworthy antitumor activity in 22 HCC PDX models positions Sora/Vino as a promising candidate for early-phase clinical trials, leveraging the established use of sorafenib and vinorelbine in HCC and other cancers.

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.

Effect of the learning curve of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on the treatment of colorectal peritoneal metastasis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are increasingly utilised in the management of colorectal peritoneal metastases (CPM). This combined modality is associated with a significant learning curve (LC) and is often criticised for its associated morbidity. This study aims to inspect the LC of this procedure in our institute. METHODS: A retrospective review of the institution's prospectively maintained database of CRS-HIPEC cases was performed. Patients treated for CPM were stratified into two groups: Group 1 consists of patients in our initial 100 cases of CRS-HIPEC and Group 2 comprises patients treated subsequently. Perioperative prognostic factors and oncological outcomes were analysed. RESULTS: Between 2001 and 2016, 77 patients with CPM underwent CRS-HIPEC, of which 31 patients (40.3%) were in Group 1 and 46 patients (59.7%) in Group 2. Median follow-up duration was 96 months in Group 1 and 25 months in Group 2. There were no differences in OS (35 months vs 46 months, p = 0.054) and DFS (13 months vs 14 months, p = 0.676) between the groups. There were more patients with higher PCI (≥12) (57.1% vs 22.2%, p = 0.006) and high-grade complications (25.8% vs 8.7%, p = 0.045) in Group 1. Group 2 patients had a shorter hospitalisation (14 days vs 11 days, p = 0.015) and SICU stay (1 day vs 0 days, p < 0.001). CONCLUSION: An improvement in the perioperative outcomes after CRS-HIPEC for CPM may be partly attributed to overcoming the LC and incorporation of better patient selection methods.

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.

Adherence of head and neck squamous cell carcinoma patients to tumor board recommendations.

BACKGROUND: Multidisciplinary team (MDT) meetings or tumor boards (TBs) are fundamental components of cancer treatment. Although their primary function is improved outcomes, this aspect is often underreported. The main objective of this study was to analyze the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) discussed at TBs, and to compare the effect of adherence and nonadherence to recommended treatment plans on outcomes. METHODS: Retrospective data analysis was conducted of HNSCC patients those who were adherent and nonadherent to TB therapy recommendations during 2008-2009 at a comprehensive cancer center. Fisher's exact test and t test were used for group-wise comparison, and Kaplan-Meier and logistic regression models, for survival analysis and determination of the contributing factors to nonadherence. RESULTS: Comprehensive Treatment plans were recommended by TBs in 293 HNSCC patients with curative intent. Seventy-two patients were excluded based on the selection criteria. Among the remaining 221 patients, 172 (77.9%) were adherent to TB recommendations, while 49 (22.1%) failed to comply. Patient (n = 36; 73.5%), clinician (n = 2; 4.1%), and disease-related (n = 11; 22.4%) factors were significant contributors to nonadherence. Mean (±standard deviation (SD)) survival time was 55.6 ± 2.32 and 29.1 ± 4 months in the adherent and nonadherent groups, (P < .0001, respectively). Multivariate analyses showed that gender, ethnicity, higher T-stage, and multimodal treatment were associated with nonadherence. CONCLUSION: Adherence to TB recommendations improved overall survival, reflecting the importance of interdisciplinary expertise in contemporary cancer treatment. Early identification and intervention is crucial in "at risk" patients to prevent subsequent drop-out from optimal cancer care.

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.

A set of molecular markers predicts chemosensitivity to Mitomycin-C following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastasis.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with significant perioperative morbidity and mortality. We aim to generate and validate a biomarker set predicting sensitivity to Mitomycin-C to refine selection of patients with colorectal peritoneal metastasis (CPM) for this treatment. A signature predicting Mitomycin-C sensitivity was generated using data from Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas. Validation was performed on CPM patients who underwent CRS-HIPEC (n = 62) using immunohistochemistry (IHC). We determined predictive significance of our set using overall survival as a surrogate endpoint via a logistic regression model. Three potential biomarkers were identified and optimized for IHC. Patients exhibiting lower expression of PAXIP1 and SSBP2 had poorer survival than those with higher expression (p = 0.045 and 0.140, respectively). No difference was observed in patients with differing DTYMK expression (p = 0.715). Combining PAXIP1 and SSBP2 in a set, patients with two dysregulated protein markers had significantly poorer survival than one or no dysregulated marker (p = 0.016). This set independently predicted survival in a Cox regression model (HR 5.097; 95% CI 1.731-15.007; p = 0.003). We generated and validated an IHC prognostic set which could potentially identify patients who are likely to benefit from HIPEC using Mitomycin-C.

Elderly Patients with Advanced Head and Neck Carcinoma: Does Aggressive Treatment Result in Better Outcomes?

OBJECTIVE: There are no well-defined treatment recommendations for elderly patients with advanced head and neck squamous cell carcinoma. This study aimed to investigate whether aggressive treatment among the elderly translated into better survival outcomes. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary institution. SUBJECTS AND METHODS: Elderly patients (≥60 years) with advanced-stage head and neck squamous cell carcinoma (stage III and IV) treated between January 1991 and May 2014 were reviewed. According to current National Comprehensive Cancer Network guidelines, they were classified to have received standard or substandard treatment. Overall survival (OS), locoregional recurrence-free survival, and distant recurrence-free survival were evaluated. RESULTS: A total of 355 patients were treated curatively: 194 with up-front surgery and 161 with radiotherapy or concurrent chemotherapy and radiotherapy. Median OS was higher among patients who received standard treatment (42.0 vs 16.0 months, P < .001). On multivariate analysis, standard treatment showed superior OS ( P < .001). Use of substandard treatment showed a hazard ratio of 2.09 (95% CI, 1.59-2.74) for poorer OS. CONCLUSION: Aggressive standard treatment protocols should be advocated for elderly patients, where comorbidities permit, as they confer better outcomes.

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.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

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.

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.

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.

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.

Morbidity and mortality of elderly patients following cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

AIM: Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is known to improve survival in selected patients with peritoneal metastasis. However, there is limited data supporting the role of CRS and HIPEC in elderly patients (≥65 years old). METHODS: A retrospective review of a prospectively maintained database of patients who underwent CRS-HIPEC between April 2001 and July 2015 from a single institution was performed. Patients were divided into two groups non-elderly (<65 years old), and elderly (≥65 years old). Clinico- pathological parameters, morbidity and overall (OS) and disease-free survival (DFS) of the patients were compared. RESULTS: A total of 177 patients (median age 52, range 9-74) underwent CRS-HIPEC with curative intent. There were 159 non-elderly patients and 18 elderly patients. Median PCI scores were 12 (0-39) for the non- elderly patients and 11 (1-29) for the elderly patients (p=0.77). High-grade complications occurred in 39 non-elderly patients (24.5%) and 8 elderly patients (44.4%) (p=0.79), while 58 non-elderly patients (38.7%) and 7 elderly patients (41.2%) stayed in ICU for more than 1 day (p=0.69). There was no difference in the 30-day mortality between the two groups (0% vs. 0%, p=1). After a median follow-up of 16 months for all patients, there was no difference in 5-years OS (51.0% vs. 59.6%, p=0.88) and 5-years DFS (23.3% vs. 53.3%, p=0.60) between non-elderly and elderly patients. CONCLUSIONS: Surgical outcomes after CRS-HIPEC do not differ significantly between non-elderly and elderly patients. Hence, age should not be a contraindication in selecting patients for CRS and HIPEC.

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.

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.