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Karin ATGM Wasmann,1 Charlotte EL Klaver,1 Jarmila DW van der Bilt,1,2 Susan van Dieren,3 Iris D Nagtegaal,4 Cornelis JA Punt,5 Bert van Ramshorst,6 Albert M Wolthuis,2 Johannes HW de Wilt,7 André D’Hoore,2 Hjalmar C van Santvoort,6 Pieter J Tanis11Department of Surgery, Amsterdam University Medical Centre, University of Amsterdam, AZ 1105, Amsterdam, The Netherlands; 2Department of Abdominal Surgery, University Hospital Leuven, Leuven 3000, Belgium; 3Clinical Research Unit, Amsterdam University Medical Centre, University of Amsterdam, AZ 1105, Amsterdam, The Netherlands; 4Department of Pathology, Radboud University Medical Centre, GA 6525, Nijmegen, The Netherlands; 5Department of Medical Oncology, Amsterdam University Medical Centre, University of Amsterdam, AZ 1105, Amsterdam, The Netherlands; 6Department of Surgery, St. Antonius Hospital, CM 3435, Nieuwegein, The Netherlands; 7Department of Surgery, Radboud University Medical Centre, GA 6525, Nijmegen, The NetherlandsPurpose: The aim of this study was to evaluate the impact of a laparoscopic approach on long-term oncological outcomes in curative intent surgery for pT4 colon cancer, in both overall and stratified subgroups with distinct clinical entities.Patients and methods: Patients with a pT4N0-2M0 colon cancer from four centers between 2000 and 2014 were included. Laparoscopic and open approaches were compared according to the intention-to-treat principle. Propensity scores were used to adjust for baseline differences between the groups in three manners: i) as a linear predictor in a Cox regression model, ii) to create a 1:1 matched cohort, and iii) to stratify patients into four groups with an increasing chance of receiving laparoscopy.Results: In total, 424 patients were included. After 1:1 matching, a laparoscopic approach correlated with higher rates of radical resection, lower morbidity, and a higher percentage of patients receiving adjuvant chemotherapy. This translated into better 5-year disease-free survival (52% vs 40%, HR 0.70; 95% CI 0.50–0.96) and 5-year overall survival (68% vs 57%, HR 0.66; 95% CI 0.43–0.99). These results were confirmed in the other two propensity score analyses. In the multivariable models, adjuvant chemotherapy remained independently associated with better survival, whereas surgical approach lost significance.Conclusions: In locally advanced colon cancer, an intentional laparoscopic approach in experienced hands seems to decrease morbidity and to increase the proportion of patients receiving adjuvant chemotherapy. Receiving adjuvant chemotherapy was independently associated with improved survival.Keywords: T4 colon cancer, laparoscopy, lower GI

It was hypothesized that colon cancer with only retroperitoneal invasion is associated with a low risk of peritoneal dissemination. This study aimed to compare the risk of metachronous peritoneal metastases (mPM) between intraperitoneal and retroperitoneal invasion. In this international, multicenter cohort study, patients with pT4bN0-2M0 colon cancer who underwent curative surgery were categorized as having intraperitoneal invasion (e.g. bladder, small bowel, stomach, omentum, liver, abdominal wall) or retroperitoneal invasion only (e.g. ureter, pancreas, psoas muscle, Gerota's fascia). Primary outcome was 5-year mPM cumulative rate, assessed by Kaplan-Meier analysis. Out of 907 patients with pT4N0-2M0 colon cancer, 198 had a documented pT4b category, comprising 170 patients with intraperitoneal invasion only, 12 with combined intra- and retroperitoneal invasion, and 16 patients with retroperitoneal invasion only. At baseline, only R1 resection rate significantly differed: 4/16 for retroperitoneal invasion only versus 8/172 for intra- +/− retroperitoneal invasion (p = 0.010). Overall, 22 patients developed mPM during a median follow-up of 45 months. Two patients with only retroperitoneal invasion developed mPM, both following R1 resection. The overall 5-year mPM cumulative rate was 13% for any intraperitoneal invasion and 14% for retroperitoneal invasion only (Log Rank, p = 0.878), which was 13% and 0%, respectively, in patients who had an R0 resection (Log Rank, p = 0.235). This study suggests that pT4b colon cancer patients with only retroperitoneal invasion who undergo an R0 resection have a negligible risk of mPM, but this is difficult to prove because of its rarity. This observation might have implications regarding individualized follow-up. [ABSTRACT FROM AUTHOR]

Abstract Objectives To investigate the impact of retroperitoneal lymphadenopathy (RPLP) on pre-operative CT scan on overall survival (OS) and disease-free survival (DFS) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal metastases (PM) of colorectal cancer. Background In patients with PM enlarged retroperitoneal lymph nodes (RPLP) are usually considered extra-regional lymph node metastases and therefore these patients may be excluded from CRS-HIPEC. This is a clinical dilemma since it is often hard to obtain histology from these nodes. Methods In this multicenter, retrospective study all consecutive patients with colorectal PM treated with CRS-HIPEC between 2004 and 2013 were included. The preoperative CT-scan was re-analyzed for the presence of RPLP based on the radiological appearance of enlarged lymph nodes. Outcomes were OS and DFS. Kaplan-Meier methods and Cox regression modeling were used to analyze the impact of RPLP on OS and DFS. Results In 25 of 401 patients (6.1%) RPLP was observed on the preoperative CT-scan. Patient, tumor and surgical characteristics did not statistically significantly differ between groups with and without RPLP. After a median follow-up of 46 months, the one-, three- and five-year survival was 80%, 59%, 38% and 90%, 50%, 36% in the group with and without RPLP respectively. Median OS (47 vs. 35 months, logrank: p = 0.70) and median DFS (14 vs. 15 months, logrank: p = 0.81) did not statistically significantly differ between groups. In multivariable analysis, RPLP did not significantly influence survival. Conclusion Enlarged retroperitoneal lymph nodes on a pre-operative CT-scan should not automatically exclude patients from CRS-HIPEC. [ABSTRACT FROM AUTHOR]

Aim The study aimed to describe the serosal microcirculation of the human bowel using sidestream dark field imaging, a microscopic technique using polarized light to visualize erythrocytes through capillaries. We also compared its feasibility to the current practice of sublingual microcirculatory assessment. Method In 17 patients sidestream dark field measurements were performed during gastrointestinal surgery. Microcirculatory parameters like microvascular flow index ( MFI), proportion of perfused vessels ( PPV), perfused vessel density ( PVD) and total vessel density ( TVD) were determined for every patient, sublingually and on the bowel serosa. Results Sixty measurements were done on the bowel of which eight (13%) were excluded, five owing to too much bowel peristalsis and three because of pressure artefacts. Image stability was in favour of sublingual measurements [pixel loss per image, bowel 145 (95% CI 126-164) vs sublingual 55 (95% CI 41-68); P < 0.001] and time to acquire a stable image [bowel 96 s (95% CI 63-129) vs sublingual 46 s (95% CI 29-64); P = 0.013]. No difference in the MFI was observed [bowel 2.9 (interquartile range 2.87-2.95) vs sublingual 3.0 (interquartile range 2.91-3.0); P = 0.081]. There was a difference in the PPV [bowel 95% (95% CI 94-96) vs sublingual 97% (95% CI 97-99); P < 0.001], PVD [bowel 12.9 mm/mm2 (95% CI 11.1-14.8) vs sublingual 17.4 mm/mm2 (95% CI 15.6-19.1); P = 0.003] and the TVD [bowel 13.6 mm/mm2 (95% CI 11.6-15.6) vs sublingual 17.7 mm/mm2 (95% CI 16.0-19.4); P = 0.008]. Conclusion Sidestream dark field imaging is a very promising technique for bowel microcirculatory visualization and assessment. It is comparable to sublingual assessment and the analysis produces a similar outcome with slightly differing anatomical features. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed to describe the pharmacokinetics of midazolam and its cytochrome P450 3A (CYP3A) mediated metabolite 1-OH-midazolam in morbidly obese patients receiving oral and i.v. midazolam before ( n = 20) and one year after weight loss surgery ( n = 18), thereby providing insight into the influence of weight loss surgery on CYP3A activity in the gut wall and liver. In a semiphysiologically based pharmacokinetic (semi-PBPK) model in which different blood flow scenarios were evaluated, intrinsic hepatic clearance of midazolam (CLint,H) was 2 (95% CI 1.40-1.64) times higher compared to morbidly obese patients before surgery ( P < 0.01). Midazolam gut wall clearance (CLint,G) was slightly lower in patients after surgery ( P > 0.05), with low values for both groups. The results of the semi-PBPK model suggest that, in patients after weight loss surgery, CYP3A hepatic metabolizing capacity seems to recover compared to morbidly obese patients, whereas CYP3A mediated CLint,G was low for both populations and showed large interindividual variability. [ABSTRACT FROM AUTHOR]

Background The Stent-In 2 trial randomized patients with malignant colonic obstruction to emergency surgery or stent placement as a bridge to elective surgery. The aim of this study was to compare the oncological outcomes. Methods Disease recurrence, and disease-free, disease-specific and overall survival were evaluated, including a subgroup analysis of patients with a stent- or guidewire-related perforation. Results Of 98 patients included in the original Stent-In 2 trial, patients with benign (16) or incurable (23) disease were excluded from this study, along with a patient who had withdrawn from the trial. Of the remaining 58 patients, 32 were randomized to emergency surgery (31 resection, 1 stoma only) and 26 to stenting. Unsuccessful stenting required emergency surgery in six patients owing to wire or stent perforation. Locoregional or distant disease recurrence developed in nine of 32 patients in the emergency surgery group and 13 of 26 in the stent group. Disease-free survival was worse in the subgroup with stent- or guidewire-related perforation. Five of six patients in this subgroup developed a recurrence, compared with nine of 32 in the emergency surgery group and eight of 20 who had unperforated stenting. Conclusion Stent placement for malignant colonic obstruction was associated with a risk of recurrence in this trial, but the numbers are small. There is not enough evidence to refute the approach strongly. Registration number: ISRCTN46462267 ( ). [ABSTRACT FROM AUTHOR]

Abstract: Aim: To compare the clinical outcome of a one-stage, primary tumour resection and hyperthermic intraperitoneal chemotherapy (HIPEC) procedure, versus a two-stage procedure of tumour resection and secondary HIPEC in colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis. Methods: A prospective database of all patients treated with HIPEC in the St. Antonius Hospital in the Netherlands between 2005 and 2012 was analysed. Results: A total of 72 patients with synchronous peritoneal carcinomatosis (PC) from CRC were included. In 20 patients (27.8%) the primary tumour was resected simultaneously with HIPEC (early referral). In the other 52 patients (72.2%) the primary tumour was resected prior to the HIPEC procedure (late referral). During CRS + HIPEC following late referral, 22 (59.5%) of the 37 anastomoses of the earlier operation were resected, revealing malignancy in 12 (54.5%) on histopathological examination. In twenty (27.8%) patients a permanent colostomy was constructed after HIPEC. Ten of these patients had complete bowel continuity after earlier primary resection. The relaparotomy rate was higher in patients after a resection of a previous anastomosis (36.4%) compared to 12% in the rest of the patients (P = 0.02). Conclusions: Resection of the primary tumour simultaneously with HIPEC in patients with synchronous PC from CRC may prevent extended bowel resections and permanent colostomy. Our data support early referral of patients with PC from colorectal cancer. [Copyright &y& Elsevier]

Objectives: Head-to-head comparison of ultrasound and CT accuracy in common diagnoses causing acute abdominal pain.Materials and Methods: Consecutive patients with abdominal pain for >2 h and <5 days referred for imaging underwent both US and CT by different radiologists/radiological residents. An expert panel assigned a final diagnosis. Ultrasound and CT sensitivity and predictive values were calculated for frequent final diagnoses. Effect of patient characteristics and observer experience on ultrasound sensitivity was studied.Results: Frequent final diagnoses in the 1,021 patients (mean age 47; 55% female) were appendicitis (284; 28%), diverticulitis (118; 12%) and cholecystitis (52; 5%). The sensitivity of CT in detecting appendicitis and diverticulitis was significantly higher than that of ultrasound: 94% versus 76% (p < 0.01) and 81% versus 61% (p = 0.048), respectively. For cholecystitis, the sensitivity of both was 73% (p = 1.00). Positive predictive values did not differ significantly between ultrasound and CT for these conditions. Ultrasound sensitivity in detecting appendicitis and diverticulitis was not significantly negatively affected by patient characteristics or reader experience.Conclusion: CT misses fewer cases than ultrasound, but both ultrasound and CT can reliably detect common diagnoses causing acute abdominal pain. Ultrasound sensitivity was largely not influenced by patient characteristics and reader experience. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the cost for prevention and treatment of pressure ulcers from a hospital perspective and to identify the least resource-intensive pressure ulcer prevention strategy.Cost analyses were examined from a hospital perspective using direct costs. The study was carried out alongside a prospective cohort study on the incidence and risk factors for pressure ulcers.Two large teaching hospitals in the Netherlands with (partly) opposing approaches in prevention, a technological versus a human approach, were analyzed.The main outcome measures were resource use, costs of preventive measures and treatment, and pressure ulcer incidence in both hospitals.Pressure ulcer prevention through a predominantly technical approach resulted in a similar incidence rate as prevention through a predominantly human approach.However, the technical approach was considerably less expensive. [ABSTRACT FROM AUTHOR]