Ferumoxytol-enhanced MR imaging for differentiating intrapancreatic splenules from other tumors.

OBJECTIVES: Ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) agent that is taken up by splenic tissue. This study describes our initial institutional experience of ferumoxytol-enhanced MRI (feMRI) for differentiating intrapancreatic splenules (IPS) from other pancreatic lesions. METHODS: In this retrospective study, patients with computed tomographic imaging that identified small enhancing lesions in the tail of the pancreas subsequently underwent feMRI for further characterization. The feMRI protocol included T2-weighted (T2w) imaging with and without fat suppression (FS), R2* mapping, diffusion-weighted imaging (DWI), and T1-weighted (T1w) imaging with FS, prior to contrast injection. Immediately after slow intravenous infusion with 3 mg/kg body weight ferumoxytol, T1w was repeated. Delayed imaging with all sequences were obtained 24-72 h after ferumoxytol administration. RESULTS: Seven patients underwent feMRI. In two patients, the pancreatic lesions were presumed as pancreatic neuroendocrine tumor (PNET) from feMRI and in the remaining 5 IPS. One of the two patients with PNET was symptomatic for NET. In another symptomatic patient with pathologically proven duodenal NET and suspected PNET, the pancreatic lesion was proven to be an IPS on feMRI. IPS demonstrated strong negative enhancement in feMRI on T2w and increased R2* values consistent with splenic tissue, while the presumed PNETs did not enhance. T2w FS was helpful on the pre-contrast images to identify IPS, while R2* did on post-contrast images. Neither DWI nor T1w contributed to differentiating PNETs from IPS. CONCLUSIONS: This study demonstrates the potential utility of feMRI as a helpful adjunct diagnostic tool for differentiating IPS from other pancreatic lesions. Further studies in larger patient cohorts are needed.

Comparison of radial 4D Flow-MRI with perivascular ultrasound to quantify blood flow in the abdomen and introduction of a porcine model of pre-hepatic portal hypertension.

OBJECTIVES: Objectives of this study were to compare radial time-resolved phase contrast magnetic resonance imaging (4D Flow-MRI) with perivascular ultrasound (pvUS) and to explore a porcine model of acute pre-hepatic portal hypertension (PHTN). METHODS: Abdominal 4D Flow-MRI and pvUS in portal and splenic vein, hepatic and both renal arteries were performed in 13 pigs of approximately 60 kg. In six pigs, measurements were repeated after partial portal vein (PV) ligature. Inter- and intra-reader comparisons and statistical analysis including Bland-Altman (BA) comparison, paired Student's t tests and linear regression were performed. RESULTS: PvUS and 4D Flow-MRI measurements agreed well; flow before partial PV ligature was 322 ± 30 ml/min in pvUS and 297 ± 27 ml/min in MRI (p = 0.294), and average BA difference was 25 ml/min [-322; 372]. Inter- and intra-reader results differed very little, revealed excellent correlation (R 2 = 0.98 and 0.99, respectively) and resulted in BA differences of -5 ml/min [-161; 150] and -2 ml/min [-28; 25], respectively. After PV ligature, PV flow decreased from 356 ± 50 to 298 ± 61 ml/min (p = 0.02), and hepatic arterial flow increased from 277 ± 36 to 331 ± 65 ml/min (p = n.s.). CONCLUSION: The successful in vivo comparison of radial 4D Flow-MRI to perivascular ultrasound revealed good agreement of abdominal blood flow although with considerable spread of results. A model of pre-hepatic PHTN was successfully introduced and acute responses monitored. KEY POINTS: • Radial 4D Flow-MRI in the abdomen was successfully compared to perivascular ultrasound. • Inter- and intra-reader testing demonstrated excellent reproducibility of upper abdominal 4D Flow-MRI. • A porcine model of acute pre-hepatic portal hypertension was successfully introduced. • 4D Flow-MRI successfully monitored acute changes in a model of portal hypertension.

Ex vivo sentinel lymph node mapping in laparoscopic resection of colon cancer.

AIM: The study examined the feasibility and potential benefit of ex vivo sentinel lymph node (SLN) mapping, including multilevel sectioning (MLS) and immunohistochemistry (IHC) in colon cancer patients undergoing laparoscopic colectomy. The secondary goals were (i) to identify patient and tumour characteristics that might influence the success of the SLN technique, (ii) to investigate the extent of lymphadenectomy required to encompass tumour-positive nonsentinel lymph nodes (NSLN) and (iii) to ascertain the association of SLN status with oncological outcomes. METHOD: SLN mapping was performed after specimen extraction using 1% Isosulfan blue. The SLNs were analysed with H&E staining after MLS, and if negative, IHC was performed. NSLNs were grouped by distance either greater than or less than 4 cm from the tumour. RESULTS: Seventy-one patients completed the study between 2003 and 2007. Using H&E with MLS, the accuracy of SLN mapping was 76%, sensitivity was 52% and the false-negative rate was 48%. Excluding patients with clinically positive lymph nodes resulted in a significant improvement in accuracy to 81% and decreased the false-negative rate to 30%. Furthermore, as the only positive NSLN > 4 cm from the tumour was grossly positive, SLN mapping with a 4-cm mesenteric cuff would have given 100% sensitivity in patients without macroscopically involved nodes. CONCLUSIONS: SLN mapping may be of value in selected patients. It may be possible to accurately stage patients with a 4-cm cuff of mesentery, although further validation of this proposal is required.

The New Beginnings Program for Divorcing and Separating Families: Moving from Efficacy to Effectiveness.

This article describes a program of research on effectively transporting the New Beginnings Program (NBP), a university-tested prevention program for divorced families, to community settings. The status of four steps in this research are described: (1) Selecting a community partner; (2) Developing effective methods of engaging parents; (3) Redesigning the NBP to be easily delivered with high quality and fidelity in community agencies, and (4) Adapting the NBP to meet the needs of the full population of divorcing families. The article concludes with a discussion of plans for an effectiveness trial to evaluate the NBP when delivered in community settings.

Histologic results 1 year after bioprosthetic repair of paraesophageal hernia in a canine model.

BACKGROUND: The use of prosthetic materials for the repair of paraesophageal hiatal hernia (PEH) may lead to esophageal stricture and perforation. High recurrence rates after primary repair have led surgeons to explore other options, including various bioprostheses. However, the long-term effects of these newer materials when placed at the esophageal hiatus are unknown. This study assessed the anatomic and histologic characteristics 1 year after PEH repair using a U-shaped configuration of commercially available small intestinal submucosa (SIS) mesh in a canine model. METHODS: Six dogs underwent laparoscopic PEH repair with SIS mesh 4 weeks after thoracoscopic creation of PEH. When the six dogs were sacrificed 12 months later, endoscopy and barium x-ray were performed, and biopsies of the esophagus and crura were obtained. RESULTS: The mean weight of the dogs 1 year after surgery was identical to their entry weight. No dog had gross dysphagia, evidence of esophageal stricture, or reherniation. At sacrifice, the biomaterial was not identifiable grossly. Biopsies of the hiatal region showed fibrosis as well as muscle fiber proliferation and regeneration. No dog had erosion of the mesh into the esophagus. CONCLUSIONS: This reproducible canine model of PEH formation and repair did not result in erosion of SIS mesh into the esophagus or in stricture formation. Native muscle ingrowth was noted 1 year after placement of the biomaterial. According to the findings, SIS may provide a scaffold for ingrowth of crural muscle and a durable repair of PEH over the long term.

Laparoscopic incisional hernia repair in a porcine model: what do transfixion sutures add?

BACKGROUND: The aim of this study was to evaluate the need for transfixion sutures during laparoscopic ventral hernia repair with mesh. METHODS: Incisional hernias were created in 14 Yucatan mini-pigs. Animals were randomized to undergo laparoscopic hernia repair either with spiral tacks alone (Tacks) or with tacks and 4 Prolene transfixion sutures (Sutured) using Composix E/X mesh (Davol Inc.). At 4 weeks, exploratory laparoscopy was performed to assess the repair and score adhesions. The abdominal wall was harvested for tensile strength analysis and histologic evaluation. Continuous variables were compared using a two-tailed nonpaired t-test. Results are presented as mean +/- standard deviation. RESULTS: The mean hernia size was 8.5 +/- 0.5 cm by 5.5 +/- 0.7 cm, with no difference between groups. The operative time was significantly longer ( p = 0.006) for the Sutured group (62.1 +/- 16.8 min) than for the Tacks group (32.3 +/- 7.0 min). The number of tacks per repair was equivalent between groups. At necropsy, the mesh in all cases was well incorporated, reperitonealized, and without evidence of migration. No hernias recurred. However, the Sutured group had a significantly ( p < or = 0.05) higher adhesion score (5.4 +/- 3.3) than the Tacks group (2.0 +/- 2.7). The tensile strength of the repair zone was no different between groups (Sutured 4.8 +/- 1.5 N/cm, Tacks 3.8 +/- 1.4 N/cm). On histologic examination, the ratio of inflammatory cells to fibroblasts was similar between groups (Sutured 0.2 +/- 0.6, Tacks 0.2 +/- 0.3). Only 82% of tacks in each group penetrated the fascia, and the depth of tack penetration was similar between groups (Sutured 3.7 +/- 0.3 mm, Tacks 3.9 +/- 0.4 mm). CONCLUSIONS: In a porcine model, the use of transfixion sutures was associated with longer operative times and more adhesions, without improvement in tensile strength or mesh incorporation. A human clinical trial is needed to determine the optimal method of securing abdominal wall mesh.

Perioperative outcomes and complications of open vs laparoscopic extraperitoneal inguinal hernia repair in a mature surgical practice.

BACKGROUND: Although the laparoscopic totally extraperitoneal (TEP) approach to hernia repair has been associated with less pain and a faster postoperative recovery than traditional open repair, many practicing surgeons have been reluctant to adopt this technique because of the lengthy operative times and the learning curve for this procedure. METHODS: Data from all patients undergoing TEP repair since 1997 and open mesh repair (OPEN) since 1999 were collected prospectively. Selection of surgical approach was based on local hernia factors, anesthetic risk, previous abdominal surgery, and patient preference. Statistical analyses were performed using unpaired t-tests and chi-squared tests. Data are mean +/- SD. RESULTS: TEP repairs were performed in 147 patients and open repairs in 198 patients. Patients in the OPEN group were significantly older (59 +/- 19 years OPEN vs 51 +/- 13 years TEP) and had a higher ASA (1.9 +/- 0.7 OPEN vs 1.5 +/- 0.6 TEP; p < 0.01). TEP repairs were more likely to be carried out for bilateral (33% TEP, 5% OPEN) or recurrent hernias (31% TEP, 11% OPEN) than were open repairs ( p < 0.01). Concurrent procedures accompanied 31% of TEP and 12% of OPEN repairs ( p < 0.01). Operative times (min) were significantly shorter in the TEP group for both unilateral (63 +/- 22 TEP, 70 +/- 20 OPEN; p = 0.02) and bilateral (78 +/- 27 TEP, 102 +/- 27 OPEN; p = 0.01) repairs. Mean operative times decreased over time in the TEP group for both unilateral and bilateral repairs ( p < 0.01). Patients undergoing TEP were more likely ( p < 0.01) to develop urinary retention (7.9% TEP, 1.1% OPEN), but were less likely ( p < 0.01) to have skin numbness (2.8% TEP, 35.8% OPEN) or prolonged groin discomfort (1.4% TEP, 5.3% OPEN). CONCLUSIONS: Despite a higher proportion of patients undergoing bilateral repairs, recurrent hernia repair, and concurrent procedures, operative times are shorter for laparoscopic TEP repair than for open mesh repair. TEP repairs can be performed efficiently and without major complications, even when the learning curve is included.

Obesity does not adversely affect the outcome of laparoscopic antireflux surgery (LARS).

BACKGROUND: Because it has been suggested that obesity adversely affects the outcome of LARS, it is unclear how surgeons should counsel obese patients referred for antireflux surgery. METHODS: A prospective database of patients undergoing LARS from 1992 to 2001 was used to compare obese and nonobese patients. Patients were surveyed preoperatively and annually thereafter. Questionnaires were completed regarding global symptoms and overall satisfaction. RESULTS: Of the 505 patients, the body mass index (BMI) was <25 (normal) in 16%, 25-29 (overweight) in 42%, and >30 (obese) in 42%. Although the operative time was longer in the obese group than in the normal weight group (137 +/- 55 min vs 115 +/- 42 min, p = 0.003), the time to discharge and rate of complications did not differ. At a mean follow-up of 35 +/- 25 months, there were no differences in symptoms, overall improvement, or patient satisfaction. Further, the rates of anatomic failure were similar among the obese, overweight, and normal weight groups. CONCLUSIONS: Although the operative time is longer in the obese, complication and anatomic failure rates are similar to those in the nonobese at long-term follow-up. Obese patients have equivalent symptom relief and are equally satisfied postoperatively. Therefore, obesity should not be a contraindication to LARS.

Influence of spastic motor disorders of the esophageal body on outcomes from laparoscopic antireflux surgery.

BACKGROUND: The clinical outcomes of laparoscopic antireflux surgery (LARS) in patients with the spectrum of nonspecific spastic esophageal motor disorders (NSSDs) are not known. METHODS: From a prospective database of patients undergoing LARS between 1997 and 2000, those with preoperative manometry at our institution and follow-up at ?6 months were identified. RESULTS: Of the 121 patients, 35 had NSSDs. There were no differences in symptoms between groups preoperatively, but in the immediate postoperative period NSSD patients had more symptoms than nonspastic patients. At 18-month mean follow-up, NSSD patients reported significantly more heartburn (22% vs 7%), waterbrash (14% vs 4%), and medication usage (17% vs 5%) than nonspastic patients (p <0.05 for each). Despite this difference, nearly all patients reported subjective improvement postoperatively, and the degree of improvement was similar between groups. CONCLUSIONS: Patients with NSSDs are more likely to have esophageal symptoms following LARS than subjects without these abnormalities. However, these patients still experience significant improvement in preoperative symptoms.

Symptomatic outcomes of laparoscopic antireflux surgery in patients eligible for endoluminal therapies.

BACKGROUND: This study compared clinical outcomes after laparoscopic antireflux surgery (LARS) in patients with gastroesophageal reflux disease (GERD) who would be eligible for endoluminal therapies (ET) with those in patients who would be excluded from ET. METHODS: From 1995 to the present, 459 patients who underwent LARS were analyzed prospectively. Of these, 117 patients (25%) without preoperative dysphagia, stricture, esophagitis worse than grade 2 or hiatal hernia larger than 2 cm were considered potential candidates for ET (group 1). By these criteria, 342 patients (75%) were not eligible for ET (group 2). Medication use and GERD symptoms were evaluated and compared between the two groups. RESULTS: Perioperative outcomes including duration of operation, morbidity, length of hospital stay and return to work were similar in the two groups. Although LARS significantly reduced medication use and GERD symptoms in both groups during a mean follow-up period longer than 2 years, there were no outcome differences between groups 1 and 2. The reported improvement in esophageal symptoms and overall satisfaction was 90% or more in both groups. CONCLUSIONS: The findings show that LARS is an effective treatment option in patients with GERD whether they are candidates for ET or not. In patients with uncomplicated GERD who currently meet inclusion criteria for ET, LARS provides excellent symptom relief and marked reduction in medication use during a mean follow-up period longer than 2 years.

Wound complications of laparoscopic vs open colectomy.

BACKGROUND: This study was conducted to determine if laparoscopic colon surgery has changed the incidence of wound complications after colon resection. METHODS: Eighty-three patients were randomized to undergo either laparoscopic (LCR) or open colon resection (OCR) for cancer at our institution as part of a multicenter trial. Data were tabulated from review of the prospective database and physician records. RESULTS: Thirty-seven patients were randomized to LCR and 46 to OCR. Seven patients in the LCR group were converted to OCR. LCR was performed using a limited midline incision for anastomosis and specimen extraction. Incision length was significantly greater (p <0.001) in the OCR group (19.4 +/- 5.6 cm) compared to the LCR extraction site (6.3 +/- 1.4 cm). Wound infections occurred in 13.5% of patients after LCR (2.7% trocar, 10.8% extraction sites) and in 10.9% of patients after OCR. Over a mean follow-up period of 30.1 +/- 17.8 months, incisional hernias developed in 24.3% of patients after LCR and 17.4% after OCR. In the LCR group, extraction sites accounted for 85.7% of all wound complications. CONCLUSIONS: The extraction site for LCR is associated with a high incidence of complications, comparable to open colectomy. Strategies to alter operative technique should be considered to reduce the incidence of these complications.

Infant and toddler pathways leading to early externalizing disorders.

OBJECTIVE: To examine pathways leading to specific types of early externalizing disorders. METHOD: Longitudinal data were collected on 310 low-income, male subjects followed from infancy until age 6 years. RESULTS: Support across informants was found for the importance of the caregiving environment during infancy in relation to the development of externalizing disorders at school entry. Support was also found for the significance of early child factors, but this was limited to child behavior at home. CONCLUSIONS: The results are consistent with social learning and attachment models, which suggest that severe conduct problems in early childhood are the result of deficits in the caregiving environment. Support was also found for Moffitt's hypothesis that children with the comorbid attention-deficit/hyperactivity disorder-oppositional defiant disorder/conduct disorder pattern experience multiple child and psychosocial risk factors that begin during infancy.

Time-lapse video reveals immediate heterogeneity and heritable damage among human ileocecal carcinoma HCT-8 cells treated with raltitrexed (ZD1694).

BACKGROUND: Cellular heterogeneity in drug response has important clinical implications, and is believed to develop over many generations during clonal evolution in human tumors. The purpose of this study was to determine the level of heterogeneity exhibited by sister cells soon after their birth. METHODS: Human ileocecal carcinoma cells (HCT-8) were followed up to 11 days in vitro after a 2-h exposure to 1 microM raltitrexed (IC(95)) in a time-lapse video system. RESULTS: Over five experiments, 414 cells were followed after exposure to raltitrexed. Immediate sterility occurred in 74% of treated cells. Only 6% of cells could produce more than two generations of offspring, and heterogeneity in drug response was seen. Comparing sister cells < 24 h old, the more proliferative sibling produced up to 73 times more offspring, with a median ratio of 9.0 (control median = 1.19). Offspring of prolific drug-treated cells had a decreased probability of division (68% compared with 92%) and an increased average interdivision time (19.0 h compared with 15.1 h). CONCLUSIONS: Short-term exposure to raltitrexed resulted in increased interdivision times and production of sterile offspring extending seven generations. Cellular heterogeneity (difference in proliferation potential comparing drug-treated sister cells) was evident without a period of clonal evolution.

Design and synthesis of substituted compounds containing the 1, 4-benzodioxin subunit. New potential calcium antagonists.

New compounds possessing 1,4-benzodioxin or its saturated analogous heterocyclic system were synthesized and tested for calcium antagonist activity. Biological differences were seen between the different modifications applied. These compounds have been shown to be representative of a novel series of calcium channel antagonists.