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Aim To compare outcome of women with ovarian metastasis who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) to outcome of women without ovarian metastasis who underwent CRS-HIPEC. Methods A prospective CRS-HIPEC database was searched to identify women with surgically treated colorectal carcinoma between 2000 and 2012. Patients with ovarian metastasis were identified and patients with peritoneal carcinomatosis but without ovarian metastasis were included as control cases. Results 75 patients with macroscopic ovarian metastasis underwent CRS-HIPEC with curative intent, while 50 female patients without ovarian metastasis were identified who underwent CRS-HIPEC. Patients with ovarian metastasis more often had a primary appendiceal tumour and had a more extensive intra-abdominal tumour load compared to patients without ovarian metastases. Median follow-up time was 45 months (95% confidence interval (CI): 37-53 months). Overall survival (OS) did not differ significantly between the two groups with a median OS in the ovarian metastasis group of 40 months (95% CI 26-54) compared to 64 months (95% CI 17-111, P = 0.478) in the non-ovarian metastasis group. Recurrence patterns did not differ significantly between groups (p = 0.183). Conclusions Patients with ovarian metastasis of colorectal and appendiceal origin who underwent CRS-HIPEC had similar outcome compared to patients without ovarian metastasis. Given the findings of high coincidence of peritoneal metastases with ovarian metastases and ovarian metastases not being an independent factor for survival after CRS-HIPEC, this procedure should be recommended for patients with peritoneal metastases and ovarian metastases of colorectal and appendiceal carcinoma. [ABSTRACT FROM AUTHOR]

Background: Treatment of newly diagnosed advanced-stage ovarian cancer typically involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to investigate whether the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery would improve outcomes among patients who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian cancer.Methods: In a multicenter, open-label, phase 3 trial, we randomly assigned 245 patients who had at least stable disease after three cycles of carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area) to undergo interval cytoreductive surgery either with or without administration of HIPEC with cisplatin (100 mg per square meter). Randomization was performed at the time of surgery in cases in which surgery that would result in no visible disease (complete cytoreduction) or surgery after which one or more residual tumors measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to be feasible. Three additional cycles of carboplatin and paclitaxel were administered postoperatively. The primary end point was recurrence-free survival. Overall survival and the side-effect profile were key secondary end points.Results: In the intention-to-treat analysis, events of disease recurrence or death occurred in 110 of the 123 patients (89%) who underwent cytoreductive surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50 to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow-up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94; P=0.02). The median overall survival was 33.9 months in the surgery group and 45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery group and 27% in the surgery-plus-HIPEC group, P=0.76).Conclusions: Among patients with stage III epithelial ovarian cancer, the addition of HIPEC to interval cytoreductive surgery resulted in longer recurrence-free survival and overall survival than surgery alone and did not result in higher rates of side effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number, NCT00426257 ; EudraCT number, 2006-003466-34 .). [ABSTRACT FROM AUTHOR]

Introduction: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) improves recurrence-free (RFS) and overall survival (OS) in patients with FIGO stage III ovarian cancer. We evaluated the effect of HIPEC on patient's health-related quality of life (HRQoL) in the OVHIPEC trial., Materials and Methods: OVHIPEC was a multicentre, open-label, randomized phase III trial for patients with stage III ovarian cancer. Patients were randomly assigned (1:1) to receive interval CRS with or without HIPEC with cisplatin. HRQoL was assessed using the EORTC QLQ-C30, and the ovarian (QLQ-OV28) and colorectal cancer (QLQ-CR38) modules. HRQoL questionnaires were administered at baseline, after surgery, after end of treatment, and every three months thereafter. HRQoL was a secondary endpoint, with the prespecified focus on the QLQ-C30 summary score and symptom scores on fatigue, neuropathy and gastro-intestinal symptoms. HRQoL was analysed using linear and non-linear mixed effect models., Results: In total, 245 patients were randomized. One-hundred-ninety-seven patients (80%) completed at least one questionnaire. No significant difference over time in the QLQ-C30 summary scores was observed between the study arms (p-values for linear and non-linear growth: p > 0.133). The pattern over time for fatigue, neuropathy and gastro-intestinal symptoms did not significantly differ between treatment arms., Conclusion: The addition of HIPEC to interval CRS does not negatively impact HRQoL in patients with stage III ovarian cancer who are treated with interval CRS due to the extent of disease. These HRQoL results, together with the improvement in RFS and OS, support the viability of HIPEC as an important treatment option in this patient population. CLINICALTRIALS., Gov Number: NCT00426257., Eudract Number: 2006-003466-34., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice., Methods: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice., Results: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies., Conclusion: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: CytoReductive Surgery and Hyperthermic IntraPEritoneal Chemotherapy (CRS-HIPEC) is now the preferred treatment of many peritoneal surface malignancies. In this retrospective study we aimed to analyze how several performance indicators changed during the first 100 CRS-HIPEC procedures in hospitals which recently introduced this treatment, and compare those with an experienced institution., Methods: The first consecutive 100 CRS-HIPEC procedures of three institutions were compared to those of the pioneer hospital. The training provided by the pioneer hospital consisted of hands-on training during the first ten procedures; hereafter guidance was available on consult basis. Operation characteristics, morbidity and completeness of cytoreduction were evaluated by case sequence. Locally-estimated-scatter-plot smoothing was used to evaluate the learning curve., Results: From four institutions 372 cases were included. A macroscopic complete cytoreduction was reached in 66% of the cases in the pioneer hospital and in 86% in the new hospitals (p < 0.001). Complete cytoreduction rates were higher at start off in the new institutions compared with the experienced institution and increased significantly in the first 100 procedures. The new hospitals started with lower morbidity than the experienced hospital, which did not significantly decrease during the study period., Conclusion: New institutions that were trained and mentored by an experienced CRS-HIPEC hospital performed better from the beginning with regard to complete cytoreduction and morbidity rate with than the experienced center. An improvement in complete cytoreduction rate during the first 100 procedures was observed in the new institutions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: To assess the results of a urinary diversion in patients who already have a colostomy or simultaneously require a (rectum) colon resection. The diversion is created from the distal part of the transected colon with a simultaneously created new colostomy contra-laterally (if necessary). This procedure is known in our institute as the 'colon shuffle'., Materials and Methods: All patients who underwent a colon shuffle in the period of 2003 and 2013 in our institute (Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital) were identified. Comorbidity was scored using the Charlson comorbidity index. Local or systemic treatment prior to surgery was reported (e.g. external beam radiotherapy, systemic chemotherapy). Surgical complications were reported according to the Clavien-Dindo classification., Results: Twenty-one patients (14 male; 7 female) underwent a colon shuffle procedure in our institute, with a mean age of 61.5 years. The majority (90.4%) of these patients had been subjected to radiotherapy on the pelvic region in the past. Although short-term complications (<30 days) were seen in 52.4% of these patients, major complications such as anastomotic leakage of the bowel and fecal peritonitis were not seen in this high-risk group of patients., Conclusion: The colon shuffle offers an elegant solution for patients who require a urinary diversion simultaneously with a colostomy or for patients who already have a colostomy from previous surgery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Population-based data on the percentage of colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis (PC) being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently lacking. The current population-based study describes trends in the use of CRS-HIPEC in the Netherlands, one of the first countries where CRS and HIPEC was introduced., Methods: All patients diagnosed with synchronous PC of CRC between 2005 and 2012 were extracted from the Netherlands Cancer Registry (n = 4623). Patients with primary appendiceal cancer were excluded resulting in a study population of 4430 patients. Trends in the use of CRS-HIPEC over time were analyzed by means of a Cochrane-Armitage trend test. Survival proportions were calculated as the time between diagnosis and date of death or last follow-up (January 2014)., Results: Of the total 4430 patients with synchronous PC, 297 (6.4%) underwent treatment with CRS-HIPEC. The proportion of colorectal PC patients receiving CRS-HIPEC increased significantly over time from 3.6% in 2005-2006 to 9.7% in 2011-2012 (p < 0.0001). Overall median survival (MS) for patients treated with CRS-HIPEC was 32.3 months, whereas MS rates were respectively 12.6, 6.1 and 1.5 for months palliative chemotherapy with/without surgery, palliative surgery and best supportive care., Conclusion: The proportion of patients diagnosed with synchronous PC from CRC treated with CRS-HIPEC has increased significantly over time and currently almost 10% of PC patients are treated with CRS-HIPEC. Median survival in this population based group is 32.3 months., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Delayed gastric emptying (DGE) is a main complication with unknown origin after a cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (CRS-HIPEC). The aim of this study was to investigate if preservation of the right gastro-epiploic artery (GEA) during standard omentectomy would have a positive effect on gastric emptying after CRS-HIPEC., Methods: Forty-two patients subjected to a CRS-HIPEC were randomized into two groups perioperatively before performing an omentectomy: in Group I (N = 21) omentectomy was performed with preservation of the GEA; in Group II (N = 21) omentectomy was performed with resection of the GEA. The primary endpoint was the number of days to full oral intake of solid food. Secondary endpoints were number of days to intended occlusion of gastrostomy catheter and total hospital admission time., Results: No significant differences were discovered between both groups in any of the study endpoints after CRS-HIPEC. No significant differences were observed in patient or operation characteristics between the randomized groups., Conclusions: No association was demonstrated between preservation of the gastro-epiploic artery during omentectomy and gastric emptying after CRS-HIPEC. The extensive intestinal manipulation or the heated intra-peritoneal chemotherapy during surgery are more plausible causes of this phenomenon. This clinical trial was registered in the Netherlands at the Central Committee on Research involving Human Subjects (CCMO) under registration number P06.0301L., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: The late revelation of ovarian cancer ensures it as the leading cause of death among gynecologic cancers. Cytoreductive surgery (CRS) and intravenous (i.v.) chemotherapy have been the cornerstone for a long time to treat this disease. More recently, the modality of intraperitoneal administration of chemotherapy under hyperthermic conditions (HIPEC) has been added. This review surveys the results of HIPEC added to CRS in ovarian cancer., Methods: A multi-database search was conducted focusing on mortality, morbidity and overall and disease-free (DF) survival rates., Results: 16 studies were identified reporting the results of CRS followed by HIPEC of 546 patients with advanced ovarian cancer. Postoperative mortality was reported for 14 out of 481 patients in total (2.9%). The major morbidity rate varied between 3.4 and 50.0%. In all but one study (533 patients), 185 events were reported (34.5%) and 21 re-interventions after 476 operations (4.4%). Survival data ranged from 10.0 to 57.1 months for the DF survival and from 19.0 to 76.1 months for the overall survival. Optimal cytoreduction and recurrent disease were associated with a better outcome in selected cases., Conclusions: Adding HIPEC to the current treatment modalities for ovarian cancer seems to be feasible. Improved survival rates have been reported at the cost of acceptable mortality rates. Nevertheless, there was a selection bias, the morbidity should not be underestimated and it is unclear yet which patient will benefit most from this treatment. Randomized controlled trials will provide an answer to this question.

Aims: Selecting patients for cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (HIPEC) remains challenging. We compared the predictive power of three intra-operative assessment tools of peritoneal involvement of colorectal cancer., Methods: Ninety-two procedures (1999-2005) were prospectively scored using the Simplified Peritoneal Cancer Index (SPCI) and 7 Region Count. The Peritoneal Cancer Index (PCI) was retrospectively scored using the SPCI tool, operative notes and pathological reports. Endpoints were completeness of cytoreduction and overall survival. Logistic regression and Receiver Operating Characteristic (ROC) curves were applied to compare the predictive value of the three scoring systems on completeness of cytoreduction., Results: After a median follow-up of 31 months, the median overall survival was 25.6 months. It decreased to 7.3 months, when cytoreduction was incomplete (p=0.001). An increased PCI, SPCI or number of regions were all associated with a decrease in probability of complete cytoreduction (p<0.05). With complete cytoreduction as outcome, the ROC areas for the PCI, SPCI and 7 Region Count were 0.92, 0.94 and 0.90, respectively (p=0.14). Using a cut-off value of 16 in the PCI system (p=0.03), 13 in the SPCI system (p=0.04) and 6 regions in the 7 Region Count (p=0.0002) the probability of complete cytoreduction decreased significantly., Conclusion: The PCI, SPCI and 7 Region Count are useful and equally effective prognostic tools predicting completeness of cytoreduction and associated improved survival. The 7 Region Count may be preferred due to its practical simplicity.

Background: Pseudomyxoma peritonei (PMP) is a rare disease with an estimated incidence of 1 per million per year, and is thought to originate usually from an appendiceal mucinous epithelial neoplasm. However it is not known exactly how often these neoplasms lead to PMP. The aim of this study is to investigate the incidence of both lesions and their relation., Methods: The nationwide pathology database of the Netherlands (PALGA) was searched for the incidence of all appendectomies, the incidence of primary epithelial appendiceal lesions and the incidence and pathology history of patients with PMP. All regarded the 10-year period of 1995-2005., Results: In the 10-year period 167,744 appendectomies were performed in the Netherlands. An appendiceal lesion was found in 1482 appendiceal specimens (0.9%). Nine percent of these patients developed PMP. Coincidentally, an additional epithelial colonic neoplasm was found in 13% of patients with an appendiceal epithelial lesion. A mucinous epithelial neoplasm was identified in 0.3% (73% benign, 27% malignant) of appendiceal specimens and 20% of these patients developed PMP. For mucocele and non-mucinous neoplasm the association with PMP was only 2% and 3%, respectively. From the nationwide database 267 patients (62 men and 205 women) with PMP were identified, which demonstrates an incidence of PMP in the Netherlands approaching 2 per million per year. The primary site was identified in 68% and dominated by the appendix (82%)., Conclusions: Primary epithelial lesions of the appendix are rare. One third of these lesions are mucinous epithelial neoplasms and especially these tumours may progress into PMP. The incidence of PMP seems to be higher than thought before. Furthermore there is a considerable risk of an additional colonic epithelial neoplasm in patients with an epithelial neoplasm at appendectomy.

Three patients, men aged 47 and 30 and a woman aged 48 years, presented with appendicitis-like symptoms, progressive abdominal distension, and an ovarian pelvic mass, respectively. All three were diagnosed with pseudomyxoma peritonei. Treatment consisted of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). After a mean follow-up of 64 months (range: 19-89) after initial treatment, the second patient had died of disease progression but the other two were alive and free of disease. Pseudomyxoma peritonei is a rare disease, characterised by progressive intraperitoneal accumulation of mucinous ascites, produced by a mucinous tumour mass on the peritoneal surfaces. The primary tumour is usually a mucinous adenoma of the appendix. Treatment by cytoreductive surgery and HIPEC can result in a 5-year survival rate of more than 80%, depending on the histopathology and the completeness of the cytoreduction. Recognising pseudomyxoma peritonei in an early stage, when complete cytoreduction is still achievable, may result in a considerable improvement in survival.

Aims: To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors., Methods: A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality., Results: The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality., Conclusions: Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.

Aim: A survival benefit has been observed for colorectal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment modality is associated with a considerable morbidity and mortality and in a significant number of patients survival is not improved. We studied whether poor survivors could be identified on preoperative computed tomography (CT), in order to avoid unnecessary surgery., Patients and Methods: Films of abdominopelvic CT scans from 25 such patients treated by cytoreductive surgery and HIPEC were retrospectively analysed by two radiologists separately. A simplified peritoneal cancer index (SPCI) was used to determine the extent of peritoneal involvement. Correlation between the on preoperative CT based SPCI-scores as well as number of involved abdominopelvic areas (N) and survival was examined with the log-rank test. The relation between each affected region and survival was evaluated with Cox regression analysis., Results: The preoperative SPCI- and N-scores of one of the radiologists had no statistically significant prognostic value, while for the second radiologist SPCI > or = 7 and N > or = 4 were associated with particularly poor outcome. Additionally, the presence of ileocaecal region involvement and, depending on the radiologist, the occurrence of tumour deposits in the left subdiaphragmatic area on CT appeared to be unfavourable prognostic signs., Conclusions: The prognostic value of preoperative conventional CT appeared to be radiologist dependent and may, therefore, be of limited value in selecting colorectal cancer patients with peritoneal carcinomatosis who will not benefit from extensive cytoreductive surgery followed by HIPEC.

Aims: To report the results of standard therapy for peritoneal carcinomatosis of colorectal origin, which consists of conventional surgery and systemic chemotherapy., Method: In a prospective study 50 patients with proven peritoneal carcinomatosis of colorectal origin were treated with conventional surgery combined with 5-fluorouracil and leucovorin, or irinotecan in patients treated by 5-fluorouracil within 12 months prior to entry. Survival and progression-free survival were studied and prognostic factors were analysed., Results: The median survival time was 12.6 months. The median time to progression was 7.6 months. Location of primary tumour and result of conventional surgery and systemic chemotherapy were prognostic factors related to survival., Conclusion: The survival time of patients with peritoneal carcinomatosis of colorectal origin seems to be increased in patients treated by conventional surgery and systemic chemotherapy when compared to minimal treatment.

Aim: The aim of this study was to determine the value of medical history and physical examination, tumour marker testing, and CT-scanning in the follow-up of patients treated for peritoneal carcinomatosis of colorectal origin., Methods: Between November 1995 and June 2003, 107 patients were treated by cytoreduction and hyperthermic intra-peritoneal chemotherapy. The treatment was considered effective if residual tumour after cytoreduction was no thicker than 2.5 mm. The follow-up consisted of history, physical examination, serum CEA and CA 19.9 testing three-monthly, and CT-scanning of the abdomen six-monthly. Location of the recurrence was categorized into intra-abdominal, hepatic, thoracic, and both intra-abdominal and systemic. The investigation that led to the detection of a recurrence was ranked according to its invasiveness and costs. The simplest investigation that could have led to the detection was marked., Results: A recurrence developed in 63 patients of the 74 patients effective initial treatment during the study period. Physical examination revealed the recurrence in 38 patients, at least one of the markers was raised above normal value in 39 patients and in 37 patients the CT-scan showed the recurrence. History and physical examination could have triggered the finding of a recurrence in 38 patients, tumour markers in 21 patients and CT-scanning in only three of the 74 recurrences., Conclusion: Physical examination and tumour marker testing detect most recurrences. CT-scanning is not an effective tool in the follow-up, and should be reserved for on-demand use.