Background Upfront cytoreductive surgery with HIPEC (CRS-HIPEC) is the standard treatment for isolated resectable colorectal peritoneal metastases (PM) in the Netherlands. This study investigates whether addition of perioperative systemic therapy to CRS-HIPEC improves oncological outcomes. Methods This open-label, parallel-group, phase II-III, randomised, superiority study is performed in nine Dutch tertiary referral centres. Eligible patients are adults who have a good performance status, histologically or cytologically proven resectable PM of a colorectal adenocarcinoma, no systemic colorectal metastases, no systemic therapy for colorectal cancer within six months prior to enrolment, and no previous CRS-HIPEC. Eligible patients are randomised (1:1) to perioperative systemic therapy and CRS-HIPEC (experimental arm) or upfront CRS-HIPEC alone (control arm) by using central randomisation software with minimisation stratified by a peritoneal cancer index of 0–10 or 11–20, metachronous or synchronous PM, previous systemic therapy for colorectal cancer, and HIPEC with oxaliplatin or mitomycin C. At the treating physician’s discretion, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. The first 80 patients are enrolled in a phase II study to explore the feasibility of accrual and the feasibility, safety, and tolerance of perioperative systemic therapy. If predefined criteria of feasibility and safety are met, the study continues as a phase III study with 3-year overall survival as primary endpoint. A total of 358 patients is needed to detect the hypothesised 15% increase in 3-year overall survival (control arm 50%; experimental arm 65%). Secondary endpoints are surgical characteristics, major postoperative morbidity, progression-free survival, disease-free survival, health-related quality of life, costs, major systemic therapy related toxicity, and objective radiological and histopathological response rates. Discussion This is the first randomised study that prospectively compares oncological outcomes of perioperative systemic therapy and CRS-HIPEC with upfront CRS-HIPEC alone for isolated resectable colorectal PM. Trial registration Clinicaltrials.gov/ NCT02758951 , NTR/ NTR6301 , ISRCTN/ ISRCTN15977568 , EudraCT/ 2016–001865-99 .

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BackgroundEndoscopic inguinal hernia repair was introduced in the Netherlands in the early 1990s. The authors’ institution was among the first to adopt this technique. In this study, long-term hernia recurrence among patients treated by the total extraperitoneal (TEP) approach for an inguinal hernia is described. A cohort study was conducted.MethodsBetween January 1993 and December 1997, 346 TEP hernia repairs were performed for 318 patients. After a mean follow-up period of 13-years, a senior resident examined each patient. An experienced surgeon subsequently examined the patients with a diagnosis of recurrent hernia. Data were collected on an intention-to-treat basis, meaning that conversions were included in the analysis. Univariant tests were used to analyze age older than 50 years, chronic obstructive pulmonary disease, body mass index, smoking habit, hernia type, history of open hernia repair, conversion, and surgeon as potential risk factors.ResultsThe analysis included 191 patients (62%) with 213 hernias. Of the original 318 patients, 59 patients died, and 68 were lost to follow-up evaluation. Perioperatively, 105 lateral, 55 medial, and 53 pantalon hernias were observed. Of the 213 hernias, 176 were primary and 37 were recurrent. The overall recurrence rate was 8.9% (8.5% for primary and 10.8% for recurrent hernias). Of the total study group, 48% of the patients experienced a bilateral inguinal hernia during their lifetime. No predicting factor for recurrent hernia could be identified.ConclusionsThe current long-term results for TEP repair of primary and secondary inguinal hernia show an overall recurrence rate of 8.9%, which is slightly higher than in previous studies. The thorough examination at follow-up assessment, the learning curve effect, and the intention-to-treat-analysis may have influenced the observed recurrence rate. Also, the percentage of bilateral hernias was higher than known to date. Therefore, examination of the contralateral side should be standard procedure.

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