CT texture analysis in colorectal liver metastases and the surrounding liver parenchyma and its potential as an imaging biomarker of disease aggressiveness, response and survival.

OBJECTIVES: To study the ratio between the CT texture of colorectal liver metastases (CRLM) and the surrounding liver parenchyma and assess the potential of various texture measures and ratios as predictive/prognostic imaging markers. MATERIALS: Seventy patients with colorectal cancer and synchronous CRLM were included. All visible metastases, as well as the whole-volume of the surrounding liver, were separately delineated on the portal venous phase primary staging CT. Texture features entropy (E) and uniformity (U) were extracted and ratios between the texture features (T) of the metastases and background liver (Tmetastases/Tliver) calculated. Texture features were compared with clinical outcome parameters: [1] extent of disease (i.e. number of metastases), [2] response to chemotherapy (in 56/70 patients who underwent chemotherapy and CT for response evaluation), and [3] overall survival. RESULTS: The Emetastases/Eliver ratio was lower in patients with limited disease (P = 0.02) and associated with overall survival, albeit not statistically significant when tested in multivariable analyses (HR 1.90; P = 0.07); Umetastases/Uliver was higher in patients with limited disease (P = 0.02). Emetastases showed a trend towards a higher value in patients that responded well to chemotherapy (P = 0.08). CONCLUSION: The ratio between the texture of liver metastases and the surrounding liver appears to reflect relevant changes in tissue microarchitecture and may be of value to assess the extent of disease and help predict overall survival.

Whole-volume vs. segmental CT texture analysis of the liver to assess metachronous colorectal liver metastases.

PURPOSE: It is unclear whether changes in liver texture in patients with colorectal cancer are caused by diffuse (e.g., perfusional) changes throughout the liver or rather based on focal changes (e.g., presence of occult metastases). The aim of this study is to compare a whole-liver approach to a segmental (Couinaud) approach for measuring the CT texture at the time of primary staging in patients who later develop metachronous metastases and evaluate whether assessing CT texture on a segmental level is of added benefit. METHODS: 46 Patients were included: 27 patients without metastases (follow-up >2 years) and 19 patients who developed metachronous metastases within 24 months after diagnosis. Volumes of interest covering the whole liver were drawn on primary staging portal-phase CT. In addition, each liver segment was delineated separately. Mean gray-level intensity, entropy (E), and uniformity (U) were derived with different filters (σ0.5-2.5). Patients/segments without metastases and patients/segments that later developed metachronous metastases were compared using independent samples t tests. RESULTS: Absolute differences in entropy and uniformity between the group without metastases and the group with metachronous metastases group were consistently smaller for the segmental approach compared to the whole-liver approach. No statistically significant differences were found in the texture measurements between both groups. CONCLUSIONS: In this small patient cohort, we could not demonstrate a clear predictive value to identify patients at risk of developing metachronous metastases within 2 years. Segmental CT texture analysis of the liver probably has no additional benefit over whole-liver texture analysis.

Retrospective observational study on the incidence of incisional hernias after reversal of a temporary diverting ileostomy following rectal carcinoma resection with follow-up CT scans.

BACKGROUND: Wounds resulting from the closure of temporary stomas have a high risk of developing an incisional hernia (IH) with incidences around 30% in studies designed to investigate this outcome. A temporary diverting ileostomy (TDI) is often used in patients after low anterior resection (LAR) for rectal cancer. METHODS: The OSTRICH study is a retrospective cohort study of rectal cancer patients who had a LAR with a reversed TDI and at least one CT scan during follow-up. Two radiologists independently evaluated all abdominal CT scans to diagnose IH at the ileostomy wound and additionally, IH at the laparotomy site. RESULTS: From the oncological database of rectal cancer patients treated from 2003 till 2012 (n = 317) a cohort of 153 patients that fulfilled the inclusion criteria was identified. Rectal cancer resection was performed by laparoscopy in 53 patients (34.6%) and by laparotomy in 100 patients (65.4%). A total of 17 IH (11.1%) was diagnosed at the former stoma site after a mean follow-up of 2.6 years. Of these, 8 IH were in patients who had a laparoscopic LAR (15.1%) and 9 IH in patients who had an open LAR (9.0%) (Fisher's exact test; p = 0.28). IH on the other abdominal wall incisions was reported in 69 patients (45.1%). Of these, 10 patients underwent laparoscopic rectal surgery (18.9%) and in 59 patients had open rectal surgery (59.0%) (Fisher's exact test; p < 0.0001). CONCLUSION: We found a lower number of incisional hernias (11.1%) after reversal of ileostomies than expected from the literature. In contrast to the findings at the ileostomy site, a very high frequency of IH (59.0%) after LAR by laparotomy was found, which was significantly higher than after laparoscopic LAR.

Retrospective observational study on the incidence of incisional hernias after colorectal carcinoma resection with follow-up CT scan.

BACKGROUND: Incisional hernia (IH) is the most frequent complication after colorectal carcinoma (CRC) resection. The incidence depends on the method of follow-up, where ultrasound yields a significant number of additional hernias compared to clinical examination alone. Not many studies have evaluated the value of computed tomography (CT) to diagnose IH. METHODS: The CorreCT study is a retrospective cohort study of IH after CRC surgery by clinical examination and by CT, as reported in the medical files. Additional independent reviewing of all CTs by two radiologists was performed. RESULTS: From the oncological database (2004-2008) of the hospital, 598 patients with CRC were identified. The data of 448 consecutive patients who underwent surgery were analyzed. Tumors were resected by laparotomy in 366 patients (81.7 %), by laparoscopy in 76 patients (17.0 %) and by laparotomy after conversion in 6 patients (1.3 %). A clinical follow-up by the surgeon in 282 patients (62.9 %) with a mean duration of 33 months, yielded 49 patients with IH (17.4 %). The mean time of IH diagnosis (T1) was 19 months. Only 16 patients (33 %) underwent a hernia repair. For 363 patients (81.0 %), CT follow-up was available for a mean period of 30 months. In 84 patients (23.1 %), an IH was diagnosed with a mean T1 of 21 months. The review of all CTs by two independent radiologists yielded additional IH in 19 and 21 patients, respectively, increasing the IH rate to 29.1 and 29.7 %, respectively, and with a decrease in mean T1 to 14 months. The inter-observer agreement between the radiologists had a Kappa-statistic of 0.73 (95 % CI 0.65-0.81). For those patients with disagreement between the radiologists, a final agreement was made during an additional reviewing session of both radiologists, increasing the IH rate to 35.0 %. Comparing clinical follow-up, routine CT follow-up, and reassessed CT follow-up we found a statistically significant difference between the three methods of IH detection (p < 0.0001). CONCLUSION: CT follow-up can identify significantly more IH than clinical examination alone, in particular if the radiologist focuses on IH development. Furthermore, we showed that focused CT evaluation diagnosed IH 7 months earlier than routine CT and 5 months earlier than clinical follow-up alone.

Single centre observational study to evaluate the safety and efficacy of the Proceed™ Ventral Patch to repair small ventral hernias.

BACKGROUND: There is evidence that mesh repair for primary umbilical hernias results in less recurrences and similar wound complication rates compared to tissue repair. In recent years, several mesh devices for the repair of small ventral hernias have been developed, but some reports have been published on serious complications and adverse effects encountered with those mesh devices. METHODS: The Proceed™ Ventral Patch (PVP™) is a partially absorbable lightweight polypropylene mesh. We introduced PVP™ in our department in April 2009 and collected patient data and outcome in an observational study of 101 consecutive patients until December 2011 (Clinical.Trials.gov: NCT01307696). In addition to the routine control 3 weeks postoperative, prospective follow-up included a questionnaire, clinical investigation and ultrasound after 12 months. RESULTS: The study included 91 primary (76 umbilical/15 epigastric) and 10 incisional ventral hernias (including 6 trocar hernias). In all patients a PVP™ with a diameter of 6.4 cm was used. Wound problems were the most frequent complication (n = 18). Follow-up of at least 12 months was achieved in 98 patients (97 %) and the mean follow-up time was 15.9 months. Follow-up by clinical examination diagnosed a recurrence in 11/92 patients (12.0 %). Only four patients were aware of their recurrent hernia, the seven others reported no problems in the questionnaire. The additional ultrasound performed did not reveal recurrences that were not already diagnosed by clinical examination. In five patients a reoperation for repair of the recurrence was performed (reoperation rate 5/98 = 5.1 %). Hernia defect size (p = 0.032) and type of hernia (p = 0.029) were found to be a significant risk factors for development of a recurrent hernia (Fisher's exact test). Hernia size was a significant risk factor both in a univariate (p = 0.005) and in a multivariate Cox model (p = 0.017). Incisional hernia was of borderline significance in a univariate (p = 0.047) and in a multivariate Cox model (p = 0.08). CONCLUSION: Intensive clinical follow-up yields a high percentage (12.0 %) of clinically proven, but often asymptomatic recurrences after repair of small ventral hernias with the PVP™. Reoperation rate for recurrence was 5.1 %. Hernia defect size is a significant risk factor for recurrence. Therefore, we recommend using the PVP™ only for primary ventral hernias smaller than 2 cm. For larger or incisional hernias other techniques allowing the use of larger meshes is advocated.

Fibromuscular dysplasia of the carotid artery.

We describe the ultrasound-Doppler and angio-CT findings of the internal carotid string-of-beads sign in a patient with fibromuscular dysplasia (FMD). FMD is a disease of unknown etiology typically affecting the medium and larger arteries of young and middle-aged women. The most commonly affected arteries are the renal arteries followed by the internal carotid arteries. The lumbar, mesenteric, celiac, hepatic and iliac arteries are less commonly affected. Patients typically present with renovascular hypertension in case of renal artery involvement, Transient ischemic attack or stroke can be one of the presenting symptoms in carotid artery involvement.

Further evidence for an association of HLA-DR7 with basal cell carcinoma on the tropical island of Saba.

OBJECTIVE: To establish the association of HLA alleles (ie, HLA-DR1, HLA-DR4, and HLA-DR7) with individuals with skin cancer on the tropical island of Saba. This island was chosen because most of the white population has fair skin and excessive exposure to sunlight, which results in a high prevalence of skin cancer. DESIGN: HLA typing was performed in 124 white individuals with histologically proven basal cell and/or squamous cell carcinoma and in control subjects. Skin type, the presence of freckling, and the number of actinic keratoses were determined. SETTING: Population-based study. SUBJECTS: Inhabitants of Saba with and without skin cancer. MAIN OUTCOME MEASURE: Presence of HLA-DR1, HLA-DR4, and HLA-DR7 alleles. RESULTS: Associations of HLA alleles with basal cell and squamous cell carcinoma have been reported. The presence of the HLA-DR7 allele was positively associated with the development of basal cell carcinoma (odds ratio, 3.8; 95% confidence interval, 1.1-13.4). Adjustment for skin type, which is a potentially confounding factor for the association between HLA alleles and skin cancer, did not substantially alter this association. No other associations between HLA alleles and skin cancer were found, possibly because of the small size of the study population. CONCLUSION: This study presented further evidence for an association between HLA-DR7 and basal cell carcinoma. Arch Dermatol. 2000;136:1019-1022

Distribution of single organ malformations in European populations. EUROCAT Working Group.

The aim of this study was to evaluate the prevalence of congenital anomalies in 19 areas from 13 European countries. A total of 291,126 births were surveyed. On average most of the anomalies were recorded in livebirths. The total prevalence of congenital anomalies was 21.8 per 10,000 births. Four groups of congenital anomalies were of particular note in the consideration of geographic variations: neural tube defects, cleft lip, limb reduction defect and Down syndrome. For neural tube defects, 24 cases per 10,000 were recorded in the British Isles whereas only 9.6 cases per 10,000 were registered in Continental Europe. Cleft lip had a much higher prevalence in Groningen (The Netherlands) and in Odense (Denmark) than in the other European countries under study. The prevalence of limb reduction defect was high in Bilbao (Spain), in Odense, in Strasbourg (France) and in Groningen. In the study population the prevalence of Down syndrome ranged from 5.6 to 21.3 per 10,000 livebirths.

Microcirculatory haemodynamics before and after vascular surgery in severe limb ischaemia--the relation to post-operative oedema formation.

To determine whether postoperative oedema could be predicted preoperatively by microcirculatory parameters, we studied nutritive capillary blood flow in 21 patients before and after limb salvage procedures. All patients had severe lower limb ischaemia and underwent femoro-popliteal or femoro-crural bypass surgery. The systolic ankle-branchial arm index and systolic toe pressure were used as macrocirculatory parameters. Intravital capillary microscopy was used to measure red blood cell (RBC) and peak RBC velocity and time to peak RBC velocity after release of a 1 min arterial occlusion in the nailfold of the toe. Transcutaneous pO2 was measured on the dorsum of the foot at rest, during oxygen inhalation and following a release of a 5 min occlusion. After surgery the mean systolic ankle-brachial index and systolic toe pressure and all transcutaneous pO2 parameters improved significantly (P less than 0.001). Mean peak RBC velocity increased from 0.156 mm/s to 0.310 mm/s (P less than 0.05), indicating that the reactive hyperaemic response in the capillary bed had improved. Eleven patients developed postoperative oedema. There were no differences in postoperative macro and microcirculatory parameters between the patients with oedema (n = 11) and those without oedema (n = 10). However, preoperatively RBC velocity and peak RBC velocity were significantly lower (P less than 0.05) and time to peak RBC velocity was significantly longer (P less than 0.01) in patients who developed oedema. These findings show that in patients with severe limb ischaemia vascular surgery improves both macro- and microcirculatory blood flow, but that these patients develop oedema after vascular surgery when microcirculatory blood flow is compromised preoperatively.

Foot salvage and improvement of microvascular blood flow as a result of epidural spinal cord electrical stimulation.

Epidural spinal cord electrical stimulation has been suggested as an alternative treatment in patients with limb-threatening ischemia in whom vascular reconstructive surgery is not possible anymore. We studied the effects of epidural spinal cord electrical stimulation on microcirculatory blood flow in 20 patients with ischemic rest pain and ulcers. Angiography showed occluded crural arteries technically unsuitable for reconstructive surgery. Intravital capillary microscopy was used to assess capillary density and diameter and red blood cell velocity before and after a 1-minute period of arterial occlusion. After epidural spinal cord electrical stimulation 18 patients claimed immediate pain relief, which was confirmed by intravital capillary microscopy. Capillary density increased from 10 to 19/mm2 (p less than 0.001), red blood cell velocity increased from 0.088 to 0.496 mm/sec (p less than 0.001), and peak red blood cell velocity after arterial occlusion increased from 0.092 to 0.548 mm/sec (p less than 0.001). Two patients had no immediate pain relief; they did not show improvement of microcirculatory perfusion, and amputation was necessary. During the follow-up period (3 months to 3 years, mean 27 months), six other patients had recurrent ischemic pain, and amputation was necessary. In 12 patients pain relief continued, and ischemic ulcers healed; capillary microscopy confirmed improved microcirculatory blood flow. Microcirculatory parameters were significantly higher in respondents than in nonrespondents (p less than 0.001). Life-table analysis revealed a cumulative foot salvage of 80% and 56% after 1 and 2 years, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of subacute oral intake of the food antioxidant butylated hydroxyanisole on clinical parameters and phase-I and -II biotransformation capacity in man.

A study is presented in which eight healthy male non-smoking volunteers ingested a daily amount of 0.5 mg/kg butylated hydroxyanisole (BHA) for 10 consecutive days. Blood samples were taken on days -6 and 0 before and on days 4 and 7 after the first BHA administration for the assessment of standard clinical plasma parameters (L-aspartate aminotransferase, L-alanine-aminotransferase, L-gamma-glutamyltranspeptidase, creatine phosphokinase, lactate dehydrogenase, total protein, albumin, urea, creatinine, Na+, and Cl-). Antipyrine (500 mg p.o.) and paracetamol (500 mg p.o) were administered before and during BHA administration as test substances to measure phase-I and phase-II biotransformation capacity. Saliva samples and urine were subsequently collected for the assessment of kinetic parameters (e.g. saliva elimination half-life, saliva clearance, apparent volume of distribution) and urinary excretion of metabolites. Kinetic plasma parameters of BHA itself were determined in plasma samples obtained via a catheter in an arm vein after oral BHA intake on days 0 and 7. Levels of antipyrine, paracetamol, BHA and metabolites in plasma, saliva or urine were quantified by standard or newly developed reversed-phase high-performance liquid chromatography methods. Urinary excretion of Na+, K+, and Cl-, as well as osmolality of urine were measured on three days before and six days during BHA administration. Generally, no significant differences were detected in the parameters measured, indicating that oral administration of BHA to men for 10 days remains without effects on clinical biochemical parameters and phase-I and phase-II biotransformation capacity. In contrast, urinary excretion of metabolites of BHA was significantly increased on days 3 and 7 vs. the first day of BHA administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiography and magnetic resonance imaging in cardiac amyloidosis.

Cardiac amyloidosis is an uncommon cause of heart failure. Based on an observation of immunocytic cardiac amyloidosis with a fatal course, the diagnostic modalities are reviewed with special emphasis on echocardiographic findings. The possible role of magnetic resonance imaging is discussed.