The impact of liver resection on the dihydrouracil:uracil plasma ratio in patients with colorectal liver metastases.

PURPOSE: The dihydrouracil (DHU):uracil (U) plasma ratio is a promising marker for identification of dihydropyrimidine dehydrogenase (DPD)-deficient patients. The objective of this study was to determine the effect of liver resection on the DHU:U plasma ratio in patients with colorectal liver metastases (CRLM). METHODS: An observational study was performed in which DHU:U plasma ratios in patients with CRLM were analyzed prior to and 1 day after liver resection. In addition, the DHU:U plasma ratio was quantified in six additional patients 4-8 weeks after liver resection to explore long-term effects on the DHU:U plasma ratio. Quantification of U and DHU plasma levels was performed using a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay. RESULTS: The median (range) DHU:U plasma ratio in 15 patients prior to liver resection was 10.7 (2.6-14.4) and was significantly reduced to 5.5 (< quantification limit (LLOQ-10.5) 1 day after resection (p = 0.0026). This reduction was caused by a decrease in DHU plasma levels from 112.0 (79.8-153) ng/mL to 41.2 (< LLOQ-160) ng/mL 1 day after resection (p = 0.0004). Recovery of the DHU:U plasma ratio occurred 4-8 weeks after liver resection, which was shown by a median (range) DHU:U plasma ratio in six patients of 9.1 (6.9-14.5). CONCLUSION: Liver resection leads to very low DHU:U plasma ratios 1 day after liver resection, which is possibly caused by a reduction in DPD activity. Quantification of the DHU:U plasma ratios directly after liver resection could lead to false-positive identification of DPD deficiency and is therefore not advised.

Surgeons' assessment versus risk models for predicting complications of hepato-pancreato-biliary surgery (HPB-RISC): a multicenter prospective cohort study.

BACKGROUND: Several studies advise the use of risk models when counseling patients for hepato-pancreato-biliary (HPB) surgery, but studies comparing these models to the surgeons' assessment are lacking. The aim of this study was to assess whether risk prediction models outperform surgeons' assessment for the risk of complications in HPB surgery. METHODS: This prospective study included adult patients scheduled for HPB surgery in three centers in the UK and the Netherlands. Primary outcome was the rate of postoperative major complications. Surgeons assessed the risk prior to surgery while blinded for the formal risk scores. Risk prediction models were retrieved via a systematic review and risk scores were calculated. For each model, discrimination and calibration were evaluated. RESULTS: Overall, 349 patients were included. The rate of major complications was 27% and in-hospital mortality 3%. Surgeons' assessment resulted in an AUC of 0.64; 0.71 for liver and 0.56 for pancreas surgery (P = 0.020). The AUCs for nine existing risk prediction models ranged between 0.57 and 0.73 for liver surgery and between 0.51 and 0.57 for pancreas surgery. CONCLUSION: In HPB surgery, existing risk prediction models do not outperform surgeons' assessment. Surgeons' assessment outperforms most risk prediction models for liver surgery although both have a poor predictive performance for pancreas surgery. REGISTRATION INFORMATION: REC reference number (13/SC/0135); IRAS ID (119370). TRIALREGISTER.NL: NTR4649.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.

Laparoscopic major hepatectomies: clinical outcomes and classification.

BACKGROUND: According to the Louisville Statement, laparoscopic major hepatectomy is a heterogeneous category that includes "traditional" trisectionectomies/hemi-hepatectomies and the technically challenging resection of segments 4a, 7, and 8. The aims of this study were to assess differences in clinical outcomes between laparoscopic "traditional" major hepatectomy and resection of "difficult-to-access" posterosuperior segments and to define whether the current classification is clinically valid or needs revision. METHODS: We reviewed a prospectively collected single-center database of 390 patients undergoing pure laparoscopic liver resection. A total of 156 patients who had undergone laparoscopic major hepatectomy according to the Louisville Statement were divided into two subcategories: laparoscopic "traditional" major hepatectomy (LTMH), including hemi-hepatectomies and trisegmentectomies, and laparoscopic "posterosuperior" major hepatectomy (LPMH), including resection of posterosuperior segments 4a, 7, and 8. LTMH and LPMH subgroups were compared with respect to demographics, intraoperative variables, and postoperative outcomes. RESULTS: LTMH was performed in 127 patients (81 %) and LPMH in 29 (19 %). Operation time was a median 330 min for LTMH and 210 min for LPMH (p < 0.0001). Blood loss was a median 500 ml for LTMH and 300 ml for LPMH (p = 0.005). Conversion rate was 9 % for LTMH and nil for LPMH (p = 0.219). In all, 28 patients (22 %) developed postoperative complications after LTMH and 5 (17 %) after LPMH (p = 0.801). Mortality rate was 1.6 % after LTMH and nil after LPMH. Hospital stay was a median 5 days after LTMH and 4 days after LPMH (p = 0.026). CONCLUSIONS: The creation of two subcategories of laparoscopic major hepatectomy seems appropriate to reflect differences in intraoperative and postoperative outcomes between LTMH and LPMH.

Topical diltiazem cream versus botulinum toxin a for the treatment of chronic anal fissure: a double-blind randomized clinical trial.

OBJECTIVE: A double-blind randomized clinical trial to compare topical diltiazem with botulinum toxin A (BTA) in the treatment of chronic anal fissure. BACKGROUND: Chronic anal fissures remain a challenging condition. Topical diltiazem and BTA are promising agents in the treatment of anal fissure. As to date diltiazem and BTA were never compared in a solid randomized trial, which is the purpose of this study. METHODS: One hundred thirty-four patients were randomized to receive either diltiazem cream and placebo injection or BTA injection and placebo cream. The primary end point was fissure healing after 3 months. RESULTS: After 3 months healing of the fissure was noted in 32 of 74 (43%) patients in the diltiazem group and 26 of 60 (43%) patients in the BTA group. Reduction >50% in mean pain score was noted in 58 of 74 (78%) patients in the diltiazem group and 49 of 60 (82%) patients in the BTA group. Perianal itching was the only side effect reported and was noted in 15% of patients in the diltiazem group, and this difference was statistically significant (P = 0.012). CONCLUSIONS: BTA yields higher healing rates in the short term, though after 3 months diltiazem and BTA resulted in equal healing rates. Also no significant difference in pain reduction was observed for both treatments. This study shows no significant advantage of one treatment compared to the other. This randomized clinical trial is registered by the Dutch Trial Register as NTR1012.

Laparoscopic liver resection for lesions adjacent to major vasculature: feasibility, safety and oncological efficiency.

BACKGROUND AND OBJECTIVES: Laparoscopic liver resection for lesions adjacent to major vasculature can be challenging, and many would consider it a contraindication. Recently, however, laparoscopic liver surgeons have been pushing boundaries and approached some of these lesions laparoscopically. We assessed feasibility, safety and oncological efficiency of this laparoscopic approach for these lesions. METHODS: This is a monocenter study (2003-2013) describing technique and outcomes of laparoscopic liver resection for lesions adjacent to major vasculature: <2 cm from the portal vein (main trunk and first division), hepatic arteries or inferior vena cava. RESULTS: Thirty-seven patients underwent laparoscopic liver resection (LLR) for a lesion adjacent to major vasculature. Twenty-four (65%) resections were for malignant disease and 92% R0 resections. Conversion occurred in three patients (8%). Mean operative time was 313 min (standard deviation (SD) ± 101) and intraoperative blood loss 400 ml (IQR 213-700). Clavien-Dindo complications > II occurred in two cases (5%), with no mortality. Lesions at <1 cm were larger (7.2 cm (2.7-14) vs. 3 cm (2.5-5), p = 0.03) and operation time was longer (344 ± 94 vs. 262 ± 92 min, p = 0.01) than lesions at 1-2 cm from major vasculature. CONCLUSIONS: Lesions <2 cm from major hepatic vasculature do not represent an absolute contraindication for LLR when performed by experienced laparoscopic liver surgeons in selected patients.

[18F]Fluorodeoxyglucose PET for Interventional Oncology in Liver Malignancy.

[(18)F]Fluorodeoxyglucose (FDG) PET is a functional imaging tool that provides metabolic information, which has the potential to detect a lesion before it becomes anatomically apparent. This ability constitutes a strong argument for using FDG-PET/computed tomography (CT) in the management of oncology patients. Many studies have investigated the accuracy of FDG-PET or FDG-PET/CT for these purposes, but with small sample sizes based on retrospective cohorts. This article provides an overview of the role of FDG-PET or FDG-PET/CT in patients with liver malignancies treated by means of surgical resection, ablative therapy, chemoembolization, radioembolization, and brachytherapy, all being liver-directed oncologic interventions.

Posttreatment PET-CT-confirmed intrahepatic radioembolization performed without coil embolization, by using the antireflux Surefire Infusion System.

Intra-arterial radioembolization with yttrium-90 microspheres is a safe and effective treatment option for patients with unresectable liver tumors. Pretreatment coil embolization of extrahepatic vessels is recommended to avoid extrahepatic deposition of radioactive microspheres. A novel infusion system with an expandable tip, the Surefire Infusion System (SIS), has recently been developed to minimize reflux. We report three cases of radioembolization with the use of the SIS. In all cases, yttrium-90 radioembolization was performed successfully without coil embolization of extrahepatic vessels. In all patients, positron emission tomography-computed tomography confirmed intrahepatic biodistribution of the microspheres in all targeted liver segments, and no extrahepatic deposition. With the use of the SIS, the need for coil embolization of extrahepatic vessels might be eliminated, and treatment may be extended to patients who were previously deemed unfit.

A prospective "oversizing" strategy of the Edwards SAPIEN bioprosthesis: results and impact on aortic regurgitation.

OBJECTIVE: Moderate to severe aortic regurgitation is occurring in 20% to 30% of cases after transcatheter aortic valve implantation. METHODS: The purpose of the study was to investigate the impact of a prospective policy of "oversizing" the Edwards SAPIEN bioprosthesis (Edwards Lifesciences LLC, Irvine, Calif) relative to the diameter of the aortic annulus on the rate and severity of aortic regurgitation in 28 consecutive patients initially considered eligible for transcatheter aortic valve implantation on the basis of angiography, multislice computed tomography, and transthoracic echocardiography. This policy included the systematic use of transesophageal echocardiography to exclude borderline patients and the modification of the procedure to use the larger device possible. The results were studied on an individual patient basis. RESULTS: Because 6 of 28 patients (21%) had an annulus diameter greater than 24 mm by transesophageal echocardiography, 22 patients underwent implantation of the Edwards SAPIEN prosthesis. In 6 of 22 patients, the procedure was adapted to follow our "oversizing" policy. As a result, the "prosthesis/annulus cover index" was 12.4% ± 4.3%. The procedure was successful in 21 of 22 patients (95%), and 18 patients were available for echocardiography at 1 month. Although a moderate to severe aortic regurgitation was observed pretreatment in 4 of 18 patients (22%), it was no longer the case at 1 month (0/18, 0%; P = .03). The improvement was secondary to a disappearance of the aortic regurgitation in all 7 patients with a significant aortic regurgitation at pretreatment, whereas the new aortic regurgitations appearing in 5 of the 11 patients with no aortic regurgitation at pretreatment were only mild aortic regurgitations. CONCLUSIONS: In patients with a successful implantation of an Edwards SAPIEN valve, a simple "oversizing" policy based on a systematic use of transesophageal echocardiography and modification of the procedure may prevent the occurrence of moderate and severe aortic regurgitations.

Intestinal perforation as an early complication in Wegener's granulomatosis.

We present the case of a young man with involvement of the gastrointestinal tract in the early phase of Wegener's granulomatosis. The patient presented at the emergency department with sudden onset of abdominal pain, nausea and vomiting. Radiography work up was negative for free air although ultrasound examination showed extraluminal intra-abdominal fluid. Exploratory laparotomy showed perforation of the jejunum. The bowel was vital except for this small segment of jejunum. A 5-cm long segment of jejunum was resected which revealed ulcerative inflammation accompanied by occluded arteries of the small intestine. Although intestinal perforation in Wegener's granulomatosis is uncommon, several cases have been previously reported. Intestinal involvement in the early phase of the disease is even more uncommon. This case combined with previously reported cases emphasizes the possibility of gastrointestinal manifestation early in Wegener's disease.