Extensive Cytoreductive Surgery Research Articles

The impact of the extent of surgery on late adverse effects following cytoreductive surgery and HIPEC

AimTo investigate the impact of the surgical extent on late adverse effects (LAE) following cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). MethodA prospective cohort study including patients undergoing CRS + HIPEC due to peritoneal metastases from gastrointestinal tumour origin. From 2006 through 2019, consecutive patients treated with CRS + HIPEC were followed at 3, 6 and 12 months, and LAEs were assessed using the symptom scales and items from the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30). Surgical extent was categorized into three groups (major, intermediate, minor) based on peritonectomy procedures and colorectal resections performed as part of CRS. EORTC data were analysed using a linear mixed effects regression model adjusted for age, gender, origin of tumour and comorbidity. ResultsIn total, 257 patients who responded to at least one questionnaire during the follow-ups were included. Only diarrhoea symptoms were positively associated with surgical extent (mean differences: major vs. minor: 8.4 (−0.5; 17.2) (p = 0.06) and major vs. intermediate: 10.9 (3.8; 18.0) (p = 0.00)). Additionally, diarrhoea symptoms persisted throughout the study period and did not change over time (mean difference 12-3 months: −3.6 (−9.1; 1.7) (p-value = 0.18)). Overall, the levels of different symptom scales (fatigue, nausea and vomiting, pain, dyspnoea, and appetite loss) significantly decreased from 3 to 12 months. ConclusionPatients undergoing extensive CRS suffer from persistent impaired gastrointestinal function in terms of diarrhoea compared patients undergoing to less extensive surgery. Attention should be directed at detecting such LAE and to guide patients accordingly.

15-month safety and efficacy data after intraperitoneal treatment with 224Radium-labelled microparticles after CRS-HIPEC for peritoneal metastasis from colorectal cancer.

3518 Background: Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis. Improved survival can be achieved by extensive cytoreductive surgery (CRS), frequently used together with hyperthermic intraperitoneal chemotherapy (HIPEC), with median time to recurrence around 12 months. Radspherin is a novel treatment principle based on the delivery of short range and cytotoxic alpha particles emitted during the decay of 224Ra. Alpha particles have high linear energy transfer and a radiation range less than 100 µm (3-10 cell diameters), generating highly localized and effective radiation with non-repairable double-strand DNA breaks in affected cells. Our hypothesis is that Radspherin produces an alpha-particle radiation field exclusively to the surfaces and liquid volumes of the peritoneum, delivering lethal doses to remaining micrometastasis in the peritoneal linings and eradicate free-floating tumor cells after surgical resection, thus assumingly prolonging time to recurrence and potentially overall survival. Methods: A phase 1/2a study (EudraCT 2018-002803-33) is ongoing to evaluate safety, tolerability and signal of efficacy of Radspherin injected intraperitoneally two days after CRS-HIPEC. After completion of dose escalation (1-2-4-7 MBq), an activity-dose of 7 MBq was recommended. Assessment of safety and efficacy (diagnostic imaging) was performed every three months. Safety data and progression-free survival (PFS) at 15 months are presented. Results: Twenty-three patients (pts) were enrolled across cohorts (safety population), of these 12 pts received the recommended dose of 7MBq, 9 pts single dose and 3 pts split dose (3,5 MBq x2). Twelve pts had synchronous PM and 11 metachronous PM. Median age was 64 years (28-78), 70 % were female and median peritoneal cancer index was 7 (3-19). To date, 271 adverse events (AE) were reported, whereof only 7 (all grade 1-2) were deemed related to Radspherin. Fourteen serious adverse events (SAEs) in 8 pts have been reported, none considered related to Radspherin. At 15 months, 9 out of 23 pts (39 %) had recurred, whereof 4 pts recurred in the peritoneum. In the expansion cohort (7MBq), 3 out of 12 pts (25 %) had recurred and none of these pts had peritoneal recurrences. Median PFS was not reached in the two populations. Conclusions: Radspherin was well tolerated with no related SAEs reported. At 15 months median PFS has not been reached and none of the patients at recommended dose had peritoneal recurrences. The results are encouraging and warrant further exploration of Radspherin as a novel treatment principle in clinical trials. Clinical trial information: NCT03732781 .

First experience with 224Radium-labeled microparticles (Radspherin®) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study).

Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis despite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). With a median time to recurrence of 11-12 months, there is a need for novel therapies. Radspherin® consists of the α-emitting radionuclide radium-224 (224Ra), which has a half-life of 3.6 days and is adsorbed to a suspension of biodegradable calcium carbonate microparticles that are designed to give short-range radiation to the serosal peritoneal surface linings, killing free-floating and/or tumor cell clusters that remain after CRS-HIPEC. A first-in-human phase 1 study (EudraCT 2018-002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin® was administered intraperitoneally 2 days after CRS-HIPEC. Dose escalation at increasing activity dose levels of 1-2-4-7-MBq, a split-dose repeated injection, and expansion cohorts were used to evaluate the safety and tolerability of Radspherin®. The aim was to explore the recommended dose and biodistribution using gamma-camera imaging. The results from the planned safety interim analysis after the completion of the dose-limiting toxicity (DLT) period of 30 days are presented. Twenty-three patients were enrolled: 14 in the dose escalation cohort, three in the repeated cohort, and six in the expansion cohort. Of the 23 enrolled patients, seven were men and 16 were women with a median age of 64 years (28-78). Twelve patients had synchronous PM stage IV and 11 patients had metachronous PM [primary stage II; (6) and stage III; (5)], with a disease-free interval of 15 months (3-30). The peritoneal cancer index was median 7 (3-19), operation time was 395 min (194-515), and hospital stay was 12 days (7-37). A total of 68 grade 2 adverse events were reported for 17 patients during the first 30 days; most were considered related to CRS and/or HIPEC. Only six of the TEAEs were evaluated as related to Radspherin®. One TEAE, anastomotic leakage, was reported as grade 3. Accordion ≥3 grade events occurred in a total of four of the 23 patients: reoperation due to anastomotic leaks (two) and drained abscesses (two). No DLT was documented at the 7 MBq dose level that was then defined as the recommended dose. The biodistribution of Radspherin® showed a relatively even peritoneal distribution. All dose levels of Radspherin® were well tolerated, and DLT was not reached. No deaths occurred, and no serious adverse events were considered related to Radspherin®.Clinical Trial Registration: Clinicaltrials.gov, NCT03732781.

Gastrointestinal pacing as a treatment of postoperative ileus following extensive surgery for peritoneal metastases - A prospective blinded randomized controlled clinical trial.

Background: Almost 10% of colorectal cancer patients present with or recur with peritoneal metastases. Currently, the only treatment with curative intent is extensive cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). More than half of patients undergoing CRS and HIPEC develop prolonged postoperative ileus (POI), defined as more than 5 days without gastrointestinal (GI) function. POI represents a major clinical challenge as it causes nausea, vomiting, stomach cramps and general discomfort for the patient. Currently no efficient treatment exists.

First experience with 224Radium-labelled microparticles (radspherin) after CRS-HIPEC for peritoneal metastasis in colorectal cancer (a phase 1 study).

3599 Background: Peritoneal metastasis (PM) from colorectal cancer carries a dismal prognosis. Improved survival can be achieved by combining extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). However, median time to recurrence is short (11-12 months) and there is a need for novel therapies to prevent subsequent PM. Radspherin consists of the α-emitting radionuclide radium-224 (224Ra), half-life 3.6 days, adsorbed to a suspension of biodegradable calcium carbonate microparticles, designed to give short-range radiation to the serosal peritoneal surface, aiming to kill remaining free cancer cells and small tumor cell clusters. Methods: A first-in-man phase 1 study (EudraCT 2018-002803-33) was conducted at two specialized CRS-HIPEC centers. Radspherin was injected in the abdominal cavity through a catheter 2 days after CRS-HIPEC. Dose escalation at increasing dose levels of 1-2-4-7-MBq, repeated injection and expansion cohorts evaluated the safety and tolerability of Radspherin, explored maximal tolerated dose and biodistribution by using single photon-emission computed tomography/computed tomography (SPECT/CT) imaging. Results from the planned safety interim analysis after completion of the dose-limiting toxicity (DLT) period are presented. Results: Twenty-three patients were enrolled, dose escalation cohort (14), repeated cohort (3) and expansion cohort (6). Nineteen patients were treated in Oslo/ 4 in Uppsala. Twelve patients had synchronous PM Stage IV and 11 metachronous PM (Stage II (6), Stage III (5). Disease-free interval 15 months (3-39); males (7), females (16); median age 64 years (28-78). Peritoneal cancer index was median 7 (3-19), operation time 395 minutes (194-515) and hospital stay 12 days (7-37). Accordion ≥3 grade events (6); including anastomotic leaks (2); abscess (1); drains (2) and missed lesion (1), all reported as serious adverse events (SAEs). The 7MBq dose was selected as recommended dose as no DLT was observed. A total of 185 treatment emergent adverse effects (TEAE) were recorded, most were of low grade and considered related to CRS and/or HIPEC. Few patients (7) had TEAEs considered related to a combined impact of Radspherin and CRS-HIPEC. The biodistribution of Radspherin showed a relatively even peritoneal distribution, and no patients had compartments of the abdominal cavity without radioactivity (cold spots), and low number had hot spots. Long-term safety, dosimetry and first efficacy results of Radspherin will be reported after 12 months follow up period. Conclusions: All dose levels of Radspherin were well tolerated with DLT not reached. No deaths occurred and no SAEs were considered related to Radspherin. The biodistribution of Radspherin showed good peritoneal distribution of the radiolabeled microparticles. Clinical trial information: 2018-002803-33.

Translational and pharmacological principles of hyperthermic intraperitoneal chemotherapy for ovarian cancer.

The long-term survival of advanced-stage ovarian cancer patients remains poor, despite extensive cytoreductive surgery, chemotherapy, and the recent addition of poly (ADP-ribose) polymerase inhibitors (PARPi). Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefit by specifically targeting peritoneal metastases, the primary site of disease recurrence. Different aspects of how HIPEC exerts its effect remain poorly understood. Improved understanding of the effects of hyperthermia on ovarian cancer cells, the synergy of hyperthermia with intraperitoneal chemotherapy, and the pharmacological and pharmacokinetic properties of intraperitoneally administered cisplatin may help identify ways to optimize the efficacy of HIPEC. This review provides an overview of these translational and pharmacological principles of HIPEC and aims to expose knowledge gaps that may direct further research to optimize the HIPEC procedure and ultimately improve survival for women with advanced ovarian cancer.

Factors predicting postoperative morbidity after cytoreductive surgery for ovarian cancer: a systematic review and meta-analysis.

ObjectiveAdvances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable.MethodsElectronic databases were searched. Meta-analysis was conducted using random-effects models.ResultsFifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001).ConclusionOur study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS.Trial RegistrationInternational Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42021282770

The impact of Enhanced Recovery after Surgery (ERAS) pathways with regard to perioperative outcome in patients with ovarian cancer

PurposeMajor surgery for ovarian cancer is associated with significant morbidity. Recently, guidelines for perioperative care in gynecologic oncology with a structured “Enhanced Recovery after Surgery (ERAS)” program were presented. Our aim was to evaluate if implementation of ERAS reduces postoperative complications in patients undergoing extensive cytoreductive surgery for ovarian cancer.Methods134 patients with ovarian cancer (FIGO I-IV) were included. 47 patients were prospectively studied after implementation of a mandatory ERAS protocol (ERAS group) and compared to 87 patients that were treated before implementation (pre-ERAS group). Primary endpoints of this study were the effects of the ERAS protocol on postoperative complications and length of stay in hospital.ResultsPreoperative and surgical data were comparable in both groups. Only the POSSUM score was higher in the ERAS group (11.8% vs. 9.3%, p < 0.001), indicating a higher surgical risk in the ERAS group. Total number of postoperative complications (ERAS: 29.8% vs. pre-ERAS: 52.8%, p = 0.011), and length of hospital stay (ERAS: 11 (6–23) vs pre-ERAS: 13 (6–50) days; p < 0.001) differed significantly. A lower fraction of patients of the ERAS group (87.2%) needed postoperative admission to the ICU compared to the pre-ERAS group (97.7%), p = 0.022). Mortality within the ERAS group was 0% vs. 3.4% (p = 0.552) in the pre-ERAS group.ConclusionThe implementation of a mandatory ERAS protocol was associated with a lower rate of postoperative complications and a reduced length of stay in hospital. If ERAS has influence on long-term outcome needs to be further evaluated.

Increased Local Inflammatory Response to MOC31PE Immunotoxin After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

BackgroundDespite extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), most patients with resectable peritoneal metastases from colorectal cancer experience disease relapse. MOC31PE immunotoxin is being explored as a novel treatment option for these patients. MOC31PE targets the cancer-associated epithelial cell adhesion molecule, and kills cancer cells by distinct mechanisms, simultaneously causing immune activation by induction of immunogenic cell death (ICD).MethodsSystemic and local cytokine responses were analyzed in serum and intraperitoneal fluid samples collected the first three postoperative days from clinically comparable patients undergoing CRS-HIPEC with (n = 12) or without (n = 26) intraperitoneal instillation of MOC31PE. A broad panel of 27 pro- and antiinflammatory interleukins, chemokines, interferons, and growth factors was analyzed using multiplex technology.ResultsThe time course and magnitude of the systemic and local postoperative cytokine response after CRS-HIPEC were highly compartmentalized, with modest systemic responses contrasting substantial intraperitoneal responses. Administration of MOC31PE resulted in changes that were broader and of higher magnitude compared with CRS-HIPEC alone. Significantly increased levels of innate proinflammatory cytokines, such as interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF) as well as an interesting time response curve for the strong T-cell stimulator interferon (IFN)-γ and its associated chemokine interferon gamma-induced protein/chemokine (C-X-C motif) ligand 10 (IP-10) were detected, all associated with ICD.ConclusionsOur study revealed a predominately local rather than systemic inflammatory response to CRS-HIPEC, which was strongly enhanced by MOC31PE treatment. The MOC31PE-induced intraperitoneal inflammatory reaction could contribute to improve remnant cancer cell killing, but the mechanisms remain to be elucidated in future studies.

Thromboembolic events post cytoreductive surgery in patients with ovarian, fallopian tube or primary peritoneal cancer

Objective: The purpose of this study was to determine the prevalence of deep vein thrombosis and pulmonary embolism after an extensive cytoreductive surgery for ovarian or fallopian tube cancer and the associated risk factors and to suggest preventive measures pre- and postoperatively to reduce these risks.

Predictive factors of postoperative complications after cytoreductive surgery for ovarian cancer

Objective: Ovarian cancer is the leading cause of death from gynecological cancer for women. The standard treatment consists of extensive cytoreductive surgery followed with adjuvant chemotherapy. This study aims to identify the common postoperative complications as well as to define predictive factors of their occurrence.

Strategies for 'bloodless' surgery: the experience of cytoreductive surgery for peritoneal carcinomatosis in Jehovah's Witnesses.

Cytoreductive surgery (CRS) for the management of peritoneal carcinomatosis (PC) can involve significant blood loss which necessitates the transfusion of blood products. This poses a particular challenge in the Jehovah's Witnesses population whose beliefs do not permit the transfusion of blood products or blood-related derivatives. This report describes the experience of one institution performing CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) for PC in Jehovah's Witnesses and perioperative management strategies employed to avoid blood transfusion. A review of literature and prospectively collated data of Jehovah's Witnesses patients who underwent extensive CRS for PC and HIPEC for PC. Four patients had CRS and HIPEC for PC. The median PC index score was 11 and complete cytoreduction was achieved in all cases. Primary tumours were ovarian (n = 1), colorectal (n = 2) and neuroendocrine tumour of gastrointestinal origin (n = 1). The median difference between preoperative and postoperative haemoglobin was 38 g/L (23-43 g/L). Strategies included acute normovolumaeic haemodilution and autotransfusion within a closed circuit, autotransfusion from cell salvage and provisions for possible use of a haemoglobin based oxygen carrier. Ancillary measures identified and implemented to minimize transfusion dependence included, but were not limited to, preoperative iron infusion, perioperative acute haemodilution and cell salvage, administration of tranexamic acid, prothrombinex and use of paediatric tubes for venepuncture. The review suggests CRS and HIPEC for extensive PC can be done safely in circumstances where transfusion of allogenic blood products is not permitted.

Pericardiobiliary fistula causing acute pericarditis and tamponade following extensive cytoreductive surgery.

Pericardiobiliary fistula causing acute pericarditis and tamponade following extensive cytoreductive surgery.

Does the addition of adjuvant intraoperative tumor bed chemotherapy during midgut neuroendocrine tumor debulking procedures benefit patients?

Midgut neuroendocrine tumor (NET) patients are often diagnosed at advanced stages with extensive mesenteric nodal and hepatic metastasis. The only potentially curative treatment is surgical tumor eradication. Despite an aggressive resection, macro and microscopic residual disease still may remain in the resection bed. We hypothesize that the application of 5-fluorouracil (5-FU) within the tumor bed will help eliminate microscopic residual disease. Records of 189 patients who underwent extensive cytoreductive surgeries during 2003-2012 for advanced, midgut NETs with extensive mesenteric lymphadenopathy were reviewed. Eighty-six patients (46%) who had 5-FU saturated gel foam strips secured into their mesenteric resection sites served as the study group and a matching 103 patients (54%) who did not have such an intra-operative chemotherapy served as controls. Survival from the time of diagnosis and post-operative complications between the two groups were compared. Mortality rates at 30, 60 and 90 days post-operatively were 4%, 0%, 0% versus 2%, 0%, 2% for study and control groups, respectively. Major complications (Grades III & IV) at the same intervals were 0, 0, 1 versus 2, 3, 2 for study and control groups, respectively. Median survival was 236 months versus 148 months for the study and control groups, respectively 24 (P=0.15). Intraoperative tumor resection bed chemotherapy is a safe adjuvant without discernible toxicity. This procedure may provide survival benefits to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery. Further study in prospective trials must be conducted to determine definitive benefit to the NET patient.

Is peritonectomy and hyperthermic intraperitoneal chemotherapy a new standard of treatment for advanced epithelial ovarian cancer?

Ovarian cancer is the leading cause of death due to gynaecological malignancy with a five-year relative survival of only 20-30% for Australian women with stage 3 and 4 disease. Most cases present with spread of cancer cells outside the pelvis to the peritoneal surfaces of the abdomen and associated viscera. Efforts to improve survival from advanced disease have therefore led to more extensive cytoreductive surgery, including the use of peritonectomy surgery, which is usually combined with hyperthermic intraperitoneal chemotherapy (HIPEC). There is an increased interest in this treatment approach by gynaecological oncologists, particularly after the results of a recent randomised controlled trial (RCT) from the Netherlands showed improved survival in women who were given HIPEC at the time of cytoreductive surgery for primary disease. This article discusses the technique of peritonectomy and HIPEC, the evidence for its use, and the potential role of this treatment approach for advanced epithelial ovarian cancer in Australian centres.

CYTOREDUCTIVE SURGERY WITH PERITONECTOMY IN PATIENTS WITH OVARIAN CANCER: TECHNICAL ASPECTS AND IMMEDIATE RESULTS

Results of numerous retrospective studies have confirmed that the degree of cytoreduction and the size of the residual tumor after the primary surgery are the most important factors affecting overall life expectancy as well as the time to progression in patients with ovarian cancer (OC). The article presents the immediate results of the first 16 extensive cytoreductive surgeries in advanced OC performed at the Oncogynecology Department of the N.N. Petrov National Medical Research Center of Oncology.

The Impact of Extensive Cytoreductive Surgery for Ovarian Cancer on the Histopathology Laboratory Workload

Objectives: Cytoreductive surgery is the principal management for ovarian cancer. Recently there has been progressive change to more extensive cytoreductive surgery (ECS) as evidence shows this improves patient prognosis. The aim of this study is to investigate the change in histopathology work load with change in surgical practice for the treatment of ovarian cancer patients at Hammersmith Hospital, UK. Materials and methods: Specimens for patients with ovarian cancer (n=116) were selected and classified into three groups: (i) standard debulking surgery; (ii) a mix of standard debulking and ECS and (iii) ECS only. The types of specimens and numbers of blocks in each group were studied. Results: Post-hoc analysis demonstrates a statistically significant increase in the number of specimens per case from standard debulking to the mixed group (p<0.0001) and to the ECS group (p<0.0001). There is also a statistically significant increase in the number of blocks from standard debulking to the mixed (p<0.0001) and to the ECS groups (p<0.0001). Conclusion: The study shows there is a significant increase in the histopathology workload with the shift from standard to extensive cytoreductive surgery, as well as increase in the complexity and range of specimens sent for histopathological examination. It is essential that centres opting for a shift to ECS ensure that adequate provisions and resources are in place to accommodate these changes.

Survival outcomes after extensive cytoreductive surgery and selective neoadjuvant chemotherapy according to institutional criteria in bulky stage IIIC and IV epithelial ovarian cancer.

ObjectiveTo investigate the survival outcomes in patients with bulky stage IIIC and IV ovarian cancer, treated by primary debulking surgery (PDS) and selective use of neoadjuvant chemotherapy (NAC) according to institutional criteria.MethodsMedical records for advanced ovarian cancer patients who were treated at National Cancer Center (NCC) between December 2000 and March 2009 were retrospectively reviewed in the comprehensive cancer center. Bulky stage IIIC and IV ovarian cancer cases were included. Current NCC indication for NAC is determined based on patients' performance status and/or computerized tomography (CT) findings indicating difficult cytoreduction. After NAC, all traces of regressed metastatic ovarian cancer, potentially including chemotherapy-resistant cancer cells, were surgically removed.ResultsOf the 279 patients with bulky stage IIIC and IV, 143 (51%) underwent PDS and 136 (49%) received NAC. No gross residual and residual tumor measuring ≤1 cm was achieved in 66% and 96% of the PDS group and 79% and 96% of the NAC group, respectively. The median progression-free survival (PFS) and overall survival (OS) time were 20 months and not reached, but might be estimated more than 70 months in the PDS group and 15 and 70 months in the NAC group, respectively.ConclusionExtensive cytoreductive surgery to minimize residual tumor and selective use of NAC based on the institutional criteria could result in improved survival outcomes. Until further studies can be done to define the selection criteria for NAC after surgery, institutional criteria for NAC should consider the ability of the surgeon and institutional capacity.

Maximal effort cytoreductive surgery for disseminated ovarian cancer in a UK setting: challenges and possibilities.

To assess surgical morbidity and mortality of maximal effort cytoreductive surgery for disseminated epithelial ovarian cancer (EOC) in a UK tertiary center. A monocentric prospective analysis of surgical morbidity and mortality was performed for all consecutive EOC patients who underwent extensive cytoreductive surgery between 01/2013 and 12/2014. Surgical complexity was assessed by the Mayo clinic surgical complexity score (SCS). Only patients with high SCS ≥5 were included in the analysis. We evaluated 118 stage IIIC/IV patients, with a median age of 63years (range 19-91); 47.5% had ascites and 29% a pleural effusion. Median duration of surgery was 247min (range 100-540min). Median surgical complexity score was 10 (range 5-15) consisting of bowel resection (71%), stoma formation (13.6%), diaphragmatic stripping/resection (67%), liver/liver capsule resection (39%), splenectomy (20%), resection stomach/lesser sac (26.3%), pleurectomy (17%), coeliac trunk/subdiaphragmatic lymphadenectomy (8%). Total macroscopic tumor clearance rate was 89%. Major surgical complication rate was 18.6% (n=22), with a 28-day and 3-month mortality of 1.7 and 3.4%, respectively. The anastomotic leak rate was 0.8%; fistula/bowel perforation 3.4%; thromboembolism 3.4% and reoperation 4.2%. Median intensive care unit and hospital stay were 1.7 (range 0-104) and 8days (range 4-118), respectively. Four patients (3.3%) failed to receive chemotherapy within the first 8 postoperative weeks. Maximal effort cytoreductive surgery for EOC is feasible within a UK setting with acceptable morbidity, low intestinal stoma rates and without clinically relevant delays to postoperative chemotherapy. Careful patient selection, and coordinated multidisciplinary effort appear to be the key for good outcome. Future evaluations should include quality of life analyses.

Chemotherapy for ovarian cancer

The standard treatment for epithelial ovarian cancer is maximal cytoreductive surgery and adjuvant chemotherapy. Neoadjuvant chemotherapy can be considered as an alternative treatment strategy when unacceptable primary surgery, in terms of gross residual tumor remaining at the end of cytoreduction, is expected or in cases where poor general condition renders extensive cytoreductive surgery unsuitable. Intraperitoneal chemotherapy is ideal for epithelial ovarian cancer because its spread is mainly limited to the peritoneal cavity. Several randomized controlled trials have reported a survival gain with intraperitoneal chemotherapy. However, disadvantages such as port-related complications, abdominal pain, and neurotoxicity hinder its wide use. Hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery has been suggested as an alternative treatment strategy for intraperitoneal chemotherapy. Ongoing clinical trials of hyperthermic intraperitoneal chemotherapy will quantify clinical outcomes in the future, such as the survival benefit in epithelial ovarian cancer.