GP41-specific antibody blocks cell-free HIV type 1 transcytosis through human rectal mucosa and model colonic epithelium.

Monostratified epithelial cells translocate HIV type 1 (HIV-1) from the apical to the basolateral surface via vesicular transcytosis. Because acutely transmitted HIV-1 is almost exclusively CCR5-tropic and human intestinal epithelial cells preferentially transcytose CCR5-tropic virus, we established epithelial monolayers using polarized HT-29 cells transduced to express CCR5, and an explant system using normal human rectal mucosa, to characterize biological parameters of epithelial cell transcytosis of HIV-1 and assess antiviral Ab blockade of transcytosis. The amount of cell-free HIV-1 transcytosed through the epithelial monolayer increased linearly in relation to the amount of virus applied to the apical surface, indicating transcytosis efficiency was constant (r(2) = 0.9846; p < 0.0001). The efficiency of HIV-1 transcytosis ranged between 0.05 and 1.21%, depending on the virus strain, producer cell type and gp120 V1-V3 loop signature. Inoculation of HIV-1 neutralizing Abs to the immunodominant region (7B2) or the conserved membrane proximal external region (2F5) of gp41 or to cardiolipin (IS4) onto the apical surface of epithelial monolayers prior to inoculation of virus significantly reduced HIV-1 transcytosis. 2F5 was the most potent of these IgG1 Abs. Dimeric IgA and monomeric IgA, but not polymeric IgM, 2F5 Abs also blocked HIV-1 transcytosis across the epithelium and, importantly, across explanted normal human rectal mucosa, with monomeric IgA substantially more potent than dimeric IgA in effecting transcytosis blockade. These findings underscore the potential role of transcytosis blockade in the prevention of HIV-1 transmission across columnar epithelium such as that of the rectum.

Endoscopic stenting versus surgical colostomy for the management of malignant colonic obstruction: comparison of hospital costs and clinical outcomes.

BACKGROUND: Although stent placement is increasingly performed, colostomy still is considered the gold standard for emergent relief of malignant colonic obstruction (MCO). This study aimed to compare hospital costs and clinical outcomes between patients undergoing colostomy and those undergoing stenting for the management of MCO. METHODS: A retrospective claims analysis of the Medicare Provider Analysis and Review (MedPAR) data set was conducted to identify inpatient hospitalizations for colostomy or stent placement for the treatment of colon cancer (2007-2008). The outcomes evaluated using MedPAR compared the total length of hospital stay (LOS) and the costs associated with both techniques. Because MedPAR is a claims data set that does not provide outcomes at a patient level, a single-institution retrospective case-control study was conducted in which each stent placement patient was matched with two colostomy patients during the same period. Outcome measures (institutional data) were used to compare rates of treatment success, postprocedure LOS, and reinterventions between the two cohorts. RESULTS: The MedPAR data evaluated 778 stent placements and 5,868 colostomy hospitalizations. There were no differences in gender, age distribution, or comorbidity between the two groups. Compared with colostomy, the median LOS (8 vs. 12 days; p<0.0001) and the median cost ($15,071 vs. $24,695; p<0.001) per claim were significantly less for stent placement. Stent placement was more commonly performed at urban versus rural hospitals (84% vs. 16%; p<0.0001), teaching versus nonteaching hospitals (56% vs. 44%; p=0.0058) and larger versus smaller institutions (mean bed capacity, 331 vs. 227; p<0.0001). The institution data included 12 patients who underwent stent placement and 24 who underwent colostomy. Although both methods were technically successful, the median postprocedure LOS (2.17 vs. 10.58 days; p=0.0004) and the rate of readmissions for complications (0% vs. 25%; p=0.01) were significantly lower for stent placement. CONCLUSION: Although the technical and clinical outcomes for colostomy and stent placement appear comparable, stent placement is less costly and associated with shorter LOS and fewer complications. Dissemination of stent placement beyond large teaching hospitals located in urban areas as a treatment for MCO is important given its implications for patient care and resource use.

Effectiveness of EUS in drainage of pelvic abscesses in 25 consecutive patients (with video).

BACKGROUND: Preliminary evidence suggests that EUS is a minimally invasive alternative to surgery and percutaneous techniques for drainage of pelvic abscesses. The EUS 2008 Working Group identified the technique as a priority for research and recommended its validation in a larger cohort of patients. OBJECTIVE: To evaluate the rates of technical and treatment success, rate of recurrence, and complications of EUS-guided drainage of a pelvic abscess in a large cohort of patients. STUDY DESIGN: Observational study. SETTING: Academic tertiary referral center. PATIENTS: Consecutive patients referred for EUS-guided drainage of a pelvic abscess that was not amenable to drainage under US or CT guidance. METHODS: In patients with an abscess that measured less than 8 cm in size, two 7F transrectal stents were deployed. In patients with an abscess that measured 8 cm or more in size, an additional 10F drainage catheter was deployed. All patients underwent follow-up CT at 36 hours to assess response to therapy. If the abscess had decreased in size by more than 50%, the drainage catheters were discontinued and patients were discharged from the hospital. The stents were then retrieved by sigmoidoscopy at 2 weeks. MAIN OUTCOME MEASUREMENTS: We evaluated the rates of technical and treatment success, rate of recurrence, and complications of the EUS-based approach. Technical success was defined as the ability to drain the abscess under EUS guidance. Treatment success was defined as symptom relief in association with complete resolution of the abscess on follow-up CT at 2 weeks. Recurrence was defined as the need for repeat EUS-guided drainage of a pelvic abscess within 90 days after the stent retrieval. RESULTS: The procedure was technically successful in all 25 patients (100%) in whom it was attempted, and no complications were encountered. Mean size of the abscess was 68.5 x 52.4 mm. In addition to transrectal stents, a drainage catheter was deployed in 10 patients. Treatment was successful in 24 (96%) of 25 patients. The mean duration of the postprocedure hospital stay was 3.2 days. At a mean follow-up of 189 days (range 93-817), all 24 patients were doing well without abscess recurrence. CONCLUSIONS: EUS is a minimally invasive, safe, and effective technique that affords long-term benefit for patients undergoing pelvic abscess drainage.

EUS-guided radiofrequency ablation with a prototype electrode array system in an animal model (with video).

BACKGROUND: Although previously reported in an animal model, the development of EUS-guided radiofrequency ablation (EUS-RFA) has been impeded because of a lack of a retractable needle electrode array that could safely and effectively ablate large areas. OBJECTIVE: To evaluate the feasibility and safety of performing EUS-RFA with a 19-gauge FNA needle fitted with an umbrella-shaped retractable needle electrode array. DESIGN AND SETTING: Endoscopic experimental study in a porcine survival model at a tertiary referral center animal laboratory. MAIN OUTCOME MEASURES: Evaluate the safety and efficacy of the retractable needle electrode array for performing EUS-RFA. INTERVENTIONS: A 19-gauge EUS-FNA needle was modified and fitted with a retractable echogenic umbrella-shaped monopolar electrode array at its tip. The FNA needle was connected to a 200-W generator that has an impedance-based feedback system. EUS-RFA of the liver was attempted on 5 Yorkshire pigs. Although 1 pig was euthanized immediately after RFA to assess for immediate complications and pathological examination, the 4 others were kept alive for 7 days. RESULTS: At EUS, the needle electrode was well visualized and could be deployed in the liver without technical difficulty. During ablation, a round hyperechoic focus gradually surrounded the electrode tip. Tissue ablation was attained within 7 minutes, and the electrode array could be easily withdrawn into the needle assembly. The vital signs of all pigs remained stable throughout the procedure and until they were euthanized. Histopathology in all pigs revealed a discrete, well-demarcated spherical focus of complete coagulation necrosis measuring 2.6 cm in diameter and without damage to the surrounding liver parenchyma or vasculature. CONCLUSIONS: In this experimental study, EUS-RFA of the liver was performed safely by using the retractable umbrella-shaped electrode array with effective coagulation necrosis of large areas.

Modified technique for EUS-guided drainage of pelvic abscess (with video).

BACKGROUND: We previously described a technique for EUS-guided drainage of pelvic abscess by means of transrectal catheter placement. However, drainage catheters are prone to accidental dislodgement, and their management has mandated a prolonged inpatient hospital stay. OBJECTIVE: To evaluate the effectiveness of a combined technique by using EUS-guided transrectal drainage catheter and stent placement for management of patients with pelvic abscesses. DESIGN: An observational study. SETTING: Academic tertiary-referral center. PATIENTS: Four patients underwent EUS-guided drainage of pelvic abscesses that were not amenable for drainage by US and/or CT guidance. INTERVENTIONS: A 10F drainage catheter and one or two 7F double-pigtail stents were deployed in the abscess cavity under EUS guidance. Subsequently, the drainage catheter was periodically flushed and aspirated for 36 hours until improvement in size of the abscess was confirmed by CT imaging. The drainage catheter was then discontinued, and the patients were discharged from the hospital. If resolution of the abscess was noted on outpatient CT at 2 weeks, then the stents were retrieved by sigmoidoscopy. MAIN OUTCOMES MEASUREMENTS: Short-term treatment success was defined as improvement in clinical symptoms and a decrease in size of the pelvic abscess on postprocedure CT obtained at 36 hours. Medium-term treatment success was defined as resolution of clinical symptoms and pelvic abscess on follow-up CT at 2 weeks. RESULTS: The procedure was technically successful in all 4 patients. The mean size of the abscess was 93 x 61 mm. No procedural complications were encountered. Treatment was successful both in the short and medium term in all 4 patients, and the mean duration of the postprocedure hospital stay was 2 days. At a mean follow-up of 221 days (range, 65-416 days), all 4 patients were doing well, without any symptoms of pelvic-abscess recurrence. LIMITATIONS: The small number of patients and the absence of a comparative treatment group. CONCLUSIONS: The combined placement of a transrectal drainage catheter and a stent under EUS guidance was a technically feasible, safe, and effective technique for management of patients with pelvic abscess. This technique minimized the possibility of accidental dislodgement of the drainage catheter and facilitated earlier patient discharge from the hospital.

Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos).

BACKGROUND: Although prior studies evaluated the role of EUS and EGD for drainage of pancreatic pseudocysts, there are no randomized trials that compared the technical outcomes between both modalities. OBJECTIVE: To compare the rate of technical success between EUS and EGD for transmural drainage of pancreatic pseudocysts. STUDY DESIGN: A prospective randomized trial. SETTING: A tertiary-referral center. PATIENTS: Those with a history of pancreatitis and symptomatic pancreatic pseudocysts that measured greater than 4 cm in size who were referred for endoscopic transmural drainage. Patients with pancreatic abscess or necrosis were excluded. MAIN OUTCOME MEASUREMENTS: Technical success was defined as the ability to access and drain a pseudocyst by placement of transmural stents. Complications were assessed at 24 hours and at day 30. Treatment success was defined as the complete resolution or decrease in size of the pseudocyst to

EUS versus surgical cyst-gastrostomy for management of pancreatic pseudocysts.

BACKGROUND: Although EUS-guided cyst-gastrostomy is increasingly being performed, there are no studies that compare the clinical outcomes and cost-effectiveness with surgical cyst-gastrostomy. OBJECTIVES: To compare the clinical outcomes of EUS-guided cyst-gastrostomy with surgical cyst-gastrostomy for the management of patients with uncomplicated pancreatic pseudocysts and to perform a cost analysis of each treatment modality. DESIGN: A retrospective case-controlled study. SETTING: A tertiary-referral center. PATIENTS: Consecutive patients with uncomplicated pancreatic pseudocysts managed by surgical and EUS-guided cyst-gastrostomy. METHODS: An independent observer blinded to all clinic outcomes matched each patient who underwent a surgical cyst-gastrostomy with 2 patients who underwent an EUS-guided cyst-gastrostomy for age, etiology of pancreatitis, and the size of the pseudocyst. MAIN OUTCOME MEASUREMENTS: Rates of treatment success, complications, and reinterventions; length of postprocedure hospital stay; and cost associated with each treatment modality. RESULTS: Ten patients (6 men; mean age 42.3 years, range 22-65 years) who underwent surgical cyst-gastrostomy were matched with 20 patients who underwent an EUS-guided cyst-gastrostomy. There were no significant differences in demographics, major comorbidities, and clinical characteristics between both cohorts. Although there were no significant differences in rates of treatment success (100% vs 95%, P = .36), procedural complications (none in either cohort), or reinterventions (10% vs 0%, P = .13) between surgery versus an EUS-guided cyst-gastrostomy, the mean length of a postprocedure hospital stay for an EUS-guided cyst-gastrostomy was significantly shorter than for surgical cyst-gastrostomy (2.65 vs 6.5 days, P = .008). The average direct cost per case for EUS-guided cyst-gastrostomy was significantly less when compared with surgical cyst-gastrostomy ($9077 vs $14,815, P = .01), which corresponded to a cost savings of $5738 per patient. LIMITATIONS: Retrospective, nonrandomized design; patients with pancreatic abscess or necrosis were not evaluated; a limited sample size and a short duration of follow-up. CONCLUSIONS: EUS-guided cyst-gastrostomy should be considered as a first-line treatment approach for patients with uncomplicated pancreatic pseudocysts, because the procedure is cost saving and is associated with a shorter length of a postprocedure hospital stay when compared with surgical cyst-gastrostomy. There was no significant difference in clinical outcomes between both treatment modalities.

Percutaneous transhepatic duodenal diversion for the management of duodenal fistulae.

PURPOSE: The aim of this study was to determine the success of the nonoperative management of persistent duodenal fistulae (DF) with percutaneous transhepatic duodenal diversion (PTDD). METHODS: Retrospective chart review identified six patients with DF managed by PTDD from 2006 to 2007. Patient outcomes and complications were assessed. RESULTS: The etiology of DF included pancreatic surgery (three patients), gastrectomy (two patients), and Crohn's disease (one patient). PTDD was performed by interventional radiology at a median time of 37 days after fistula recognition. After PTDD, fistula drainage decreased from 775 cc/day (range 200 to 2,525 cc/day) to <50 cc/day at a median of 8 days. Patients were discharged 32 days (median) after PTDD. One patient with Crohn's disease required definitive surgical treatment. Of the remaining five patients, the PTDD tube was capped at 27 days (median) after placement and was removed on an outpatient basis at 79 days (median) after placement. There was no mortality, no fistula recurrence, or complications associated with PTDD placement. CONCLUSIONS: We present an algorithm for the nonoperative management of persistent postoperative DF. In this limited series, PTDD was highly effective at definitively treating DF, especially in the acute setting. PTDD should be considered by surgeons facing the management of postoperative DF.

Ileorectal anastomosis for slow transit constipation: long-term functional and quality of life results.

The results of colectomy and ileorectal anastomosis (IRA) in patients diagnosed by physiologic testing as having slow transit constipation (STC) have been reported. The durability of functional results and long-term quality of life (QoL) in these patients, however, has not been established. Between 1987 and 2002, 3670 patients were evaluated for constipation at our institution; 110 (3%) fulfilled the criteria for STC and underwent an IRA. Patients were prospectively followed and functional outcomes assessed annually by standardized questionnaires. After a median follow-up of 11 years, 104 eligible patients were mailed validated questionnaires to assess functional outcomes and QoL (Knowles-Eccersley-Scott Symptom [KESS] score, the Irritable Bowel Syndrome Quality of Life [IBS-QOL], and the SF-12 health survey). Prospectively assessed functional data was available on 85 of 104 (82%) eligible patients. At last follow-up, improvement of constipation and satisfaction with bowel function was reported by 98% and 85% of patients, respectively. Performance measures including social activity, household work, sexual life, and family relationships were reported to have improved or were not affected as a result of surgery by 75%, 86%, 81%, and 86% of the patients respectively. Fifty-nine patients (57%) responded to the study questionnaires. All 59 patients reported their constipation to be better since IRA, 83% did not require any medication, and 85% reported being satisfied with bowel function. The KESS scores of patients undergoing IRA for STC (median 6, range 0-35) were lower than reported scores of STC patients not operated upon (median 21, range 11-35, P<0.001) indicating symptomatic improvement after surgery. Mean IBS-QOL scores were similar to reported scores of patients undergoing IRA for other conditions [80 (23) versus 84 (16)], P=0.7). Mean SF-12 physical and mental summary scores were similar to reported SF-12 scores of the normal population (49.5 versus 50 and P=0.70, 48.7 versus 50, P=0.42, respectively). Ileorectal anastomosis in appropriately selected patients with slow transit constipation results in durable symptomatic relief and a long-term quality of life indistinguishable from the general population.

Patient perception of natural orifice transluminal endoscopic surgery as a technique for cholecystectomy.

BACKGROUND: Although the concept of natural orifice transluminal endoscopic surgery (NOTES) as a minimally invasive surgical technique is gaining increasing popularity, patient perception toward NOTES is unclear. Because cholecystectomy is the most common laparoscopic procedure, the concept of NOTES was examined in this context. AIM: To evaluate patient perception of NOTES as a potential technique for a cholecystectomy. PATIENTS: Those patients with an intact gallbladder who were undergoing an EUS or an ERCP for evaluation of abdominal pain, pancreatitis, or suspected choledocholithiasis. SETTING: Tertiary-referral center. DESIGN: Cross-sectional survey. METHODS: One hundred patients were given a questionnaire that described the technique, the complication rates, and benefits of laparoscopic cholecystectomy (LC). The concept of NOTES was then described in detail, with possible orifices being the mouth, the rectum, and the vagina. Patients were queried about their preference for a cholecystectomy technique (LC vs NOTES), choice of orifice, and the risks that they were willing to undergo for NOTES. RESULTS: Of the 100 patients, 78% preferred NOTES, and 22% preferred LC. The mean age of the patients was 45 years; 36% of patients were men, 70% were white, and 83% had undergone a prior endoscopy; no significant differences were observed between the NOTES and LC groups for these characteristics. In multivariable modeling, those with age

EUS-guided drainage of pelvic abscess (with video).

BACKGROUND: Although pelvic abscesses have traditionally been drained by surgery or under radiologic guidance, a small subset of patients who are not candidates for these interventions require an alternate mode of drainage. OBJECTIVE: Evaluate the efficacy of EUS for drainage of pelvic abscesses that could not be drained under US or CT guidance. DESIGN: Prospective case series. SETTING: Tertiary referral center. PATIENTS: Four patients underwent EUS-guided drainage of pelvic abscesses that were not amenable for drainage by US and/or CT guidance. INTERVENTIONS: A 10F drainage catheter was deployed in the abscess cavity under EUS guidance in all patients. The catheters were flushed periodically until resolution of the abscess was confirmed by CT imaging. MAIN OUTCOME MEASUREMENTS: Resolution of a pelvic abscess on follow-up CT and improvement in clinical symptoms. RESULTS: A drainage catheter was successfully placed in all 4 patients. The mean size of the abscess was 68 x 72 mm. There were no procedure-related complications. One patient died of worsening congestive heart failure 48 hours after the procedure. The abscesses resolved in the remaining 3 patients within a mean duration of 6 days, with complete symptom relief. LIMITATIONS: A small number of patients and short duration of follow-up. CONCLUSIONS: EUS-guided placement of drainage catheter is a minimally invasive technique for draining pelvic abscesses that are within the reach of the echoendoscope.

Maternal and fetal outcome after colectomy for fulminant ulcerative colitis during pregnancy: case series and literature review.

PURPOSE: Previous studies have reported high morbidity and mortality in mothers and their offspring after colectomy for ulcerative colitis during pregnancy. This study was designed to assess the maternal and fetal outcomes of pregnant females undergoing colectomy for ulcerative colitis in the current era. METHODS: A retrospective analysis was performed at our institution of all pregnant females undergoing operation for ulcerative colitis between 1980 and 2004. To compare this data to that of past literature, a MEDLINE search from 1951 to 2004 reviewed all cases reported on this topic. RESULTS: Between 1980 and 2004, five females underwent an operation at our institution for fulminant ulcerative colitis while pregnant. All five patients underwent subtotal colectomy with Brooke ileostomy. Postoperative maternal morbidity included a superficial wound infection and a small asymptomatic intra-abdominal abscess. All females had successful pregnancies, and no maternal or fetal deaths occurred. Two patients went on to have an ileal pouch-anal anastomosis, one had a completion proctectomy and end ileostomy, one is scheduled for an ileal pouch-anal anastomosis, and one patient is lost to follow-up. The literature review revealed 37 cases. The overall fetal and maternal mortality was 49 and 22 percent respectively. Postoperative maternal morbidity was reported in 24 percent. CONCLUSIONS: In contrast to historic data, the maternal and fetal mortality from our series was zero and maternal morbidity was low. Subtotal colectomy and Brooke ileostomy for ulcerative colitis during pregnancy is safe. A multidisciplinary team that includes a gastroenterologist, high-risk obstetrician, and experienced surgeon is necessary for an optimal outcome.