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.

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.

Cell cycle studies of cyclocreatine, a new anticancer agent.

Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK), exhibits antitumor activity in vitro and in vivo. To address its mechanism of action, we have examined its effects on tumor cell proliferation, viability, and cell cycle progression. Complete inhibition of proliferation of ME-180 cervical carcinoma cells was observed within 8 h of exposure to CCr and was characterized by an inhibition of progression out of all phases of the cell cycle. This initial effect was partially reversible on drug removal. Increased cytotoxicity was observed after several days of drug exposure and was most specific to cells in S. Previous studies have shown that CCr supports ATP regeneration through the CK system less efficiently than the natural substrate creatine and that CCr is active against tumor cell lines with elevated levels of CK. We propose here that the general inhibition of cell cycle progression reflects an effect of CCr on tumor cell energy availability through CK and that impaired energy homeostasis for several days leads to tumor cell death. Our results point out the unique nature of CCr as an anticancer agent that inhibits progression out of all phases of the cell cycle.

3,5,3'-triiodothyronine (T3) receptor-auxiliary protein (TRAP) binds DNA and forms heterodimers with the T3 receptor.

Nuclear factors enhance binding of T3 receptors (TR) to DNA, suggesting that T3 action may require a multicomponent complex bound to thyroid hormone response elements (TREs). We refer to the 65,000 Da nuclear protein in GH3 cells that enhances TR binding to DNA as the TR-auxiliary protein (TRAP) and have characterized its interaction with TR. Using a TRE-DNA affinity matrix we show that TRAP is able to bind to DNA, even in the absence of functional TR. We then used carboxyl-terminal truncations of rat TR alpha-1 and human TR beta in the avidin-biotin complex DNA-binding assay to identify regions that are important for interaction with TRAP. Removal of 34 residues of hTR beta abolishes T3-binding activity, but the ability to bind TRAP is retained. Further truncations and point mutations suggest that TRAP interacts with the ligand-binding domain of TR and with an independent region which overlaps a conserved sequence adjacent to the second Zn2+ finger (amino acids 120-149 in rTR alpha-1). A fragment of rTR alpha-1 (alpha C291) which encompasses these two regions inhibits the ability of TRAP to enhance TR binding to DNA. This is due to binding of alpha C291 to TR, demonstrating the ability of TR to form homodimers. The inability of TRAP to interact with TR dimers and the similarity of the locations of the estradiol receptor dimerization domains with the TRAP interaction regions lead us to conclude that TRAP stabilizes TR binding to DNA by formation of TRAP-TR heterodimers with both proteins bound to the DNA. TR bound to the estrogen response element is unable to respond to TRAP and unable to stimulate transcription, possibly due to the absence of TRAP in the TR-estrogen response element complex. In addition, TRAP may interact with a certain subset of the nuclear receptor superfamily, since human retinoic acid receptor-beta and vitamin D receptor show increased binding to TREs in the presence of nuclear extract, but c-erbA alpha-2, a variant TR, does not respond to TRAP.