Yaron Perry

Comparing the Outcomes after Laparoscopic versus Open Gastric Bypass: a Matched Paired Analysis

Background: Laparoscopic gastric bypass (LGBP) is being performed widely as a treatment of choice for morbid obesity. Advantages over open gastric bypass (OGBP) have not been well documented in controlled studies. The aim of this study is to evaluate the early postoperative outcomes after LGBP and OGBP using a matched paired analysis. Methods: 80 consecutive LGBP patients were matched by age, gender, preoperative BMI, and number of co-morbid medical conditions to 80 OGBP patients. Outcomes included length of stay (LOS), complications, percent excess weight lost (%EWL) and change in BMI over 1 year, time to return to normal activities, and quality of life (QOL). Continuous variables were analyzed using Wilcoxon Signed Ranks and discrete data were analyzed with McNemar tests. Results: Baseline variables were matched (LGBP/OGBP); age 43/42, mean preoperative BMI 44/46, co-morbid conditions 2.5/2.8. LOS was significantly shorter in the LGBP vs. OGBP group (3.6 vs. 4.3 days). There was a trend to more major complications (internal hernias requiring reoperation) in the LGBP group that did not reach significance. Minor complications were comparable. %EWL was significantly better in the LGBP group at 3, 6, and 9 months, but was comparable to the OGBP group at 1 year (LGBP/OGBP, 69%/65%). BMI at 1 year was also similar (29 vs. 31). LGBP patients returned to normal activities sooner and had equivalent QOL outcomes. Conclusion: LGBP provides certain advantages over OGBB. LOS and time to return to normal activities are shorter and early weight loss results may be superior.

Outcomes of minimally invasive esophagectomy (MIE) for high-grade dysplasia of the esophagus

OBJECTIVE The management of high-grade dysplasia (HGD) of the esophagus is controversial with some clinicians advocating non-operative ablation or surveillance. Minimally invasive esophagectomy (MIE) allows re-section of the esophagus and may minimize morbidity. This report summarizes our experience with MIE for HGD. METHODS A retrospective review of 28 patients who underwent MIE for a pre-operative diagnosis of HGD. MIE initially involved a laparoscopic transhiatal approach (n=1), but subsequently evolved to laparoscopy with VATS mobilization (n=27) of the esophagus. RESULTS From August 1996 to March 2001, 28 patients underwent MIE. There were 23 males and five females; median age was 61 (40-78) years. Median hospital stay was 5 (3-20) days and ICU stay was 1 (1-20) day. One patient required conversion to laparotomy because of dense adhesions. There were ten other patients who had successful MIE despite prior laparotomy. Median operating time was 8 (5.8-13) h. One death occurred from sepsis, pneumonia and multi-system organ failure. Complications occurred in 15 patients. In addition to the patient who died, five re-operations were required for: small bowel perforation (n=1), jejunostomy leak (n=1), pyloric dilation for gastric outlet obstruction (n=1), cholecystectomy (n=1), incision and drainage of an abdominal abscess (n=1). Final pathologies were HGD (n=17), in situ cancer (n=6) and invasive cancer (n=5). At a median follow-up of 13 (2-41) months all hospital survivors are alive and free of disease. CONCLUSIONS This report confirms the risk of occult cancer in patients with HGD (39% in this series) supporting the recommendation for esophagectomy. MIE can be performed with acceptable results and may minimize morbidity compared to previous reports of open esophagectomy for HGD.

Three-field minimally invasive esophagectomy: current results and technique.

The adoption of minimally invasive esophagectomy has increased worldwide since its first description more than 15 years ago. The technique has evolved from a transhiatal to a 3-hole McKeowan approach and, more recently, to a minimally invasive Ivor Lewis approach. We reviewed the technique and results of 3-hole minimally invasive esophagectomy. We favor thoracoscopic esophageal mobilization with the patient in a lateral decubitus position, although other groups have reported this with a prone or robotic approach. Several series have demonstrated low perioperative mortality with minimally invasive esophagectomy. A major advantage compared with esophagectomy with thoracotomy is a lower incidence of respiratory complications, which have been shown to be a significant predictor of mortality in other studies.

Port Placement for Minimally Invasive Esophagectomy

Two different minimally invasive approaches to esophagectomy are presented in this chapter; in both methods the intraabdominal portion of the case is carried out laparoscopically. The first method, the transhiatal approach, avoids entry into the chest; in this case the operation is completed via a neck incision. In contrast, the second method calls for part of the case to be completed via thoracoscopic means. Regardless, a single port arrangement suffices for the transabdominal portion of both the transhiatal and the thoracoscopic/laparoscopic esophagectomy.

671. Overexpression of Manganese Superoxide Dismutase (MnSOD) Prevents Photodynamic Therapy (PDT)-Induced Porcine Esophageal Stricture

Photodynamic therapy (PDT) is used in treatment of esophageal cancer and for ablation of Barretts esophagus. A complication of this procedure is esophageal stricture. We sought to determine whether overexpression of MnSOD prevented formation of PDT-induced esophageal stricture in a pig model. Pigs were injected intravenously with Photofrin (2 mg/kg) and MnSOD-PL complex (10 mg plasmid DNA) by an endoscope placed either at the site of PDT treatment (10 cm from gastroesophageal (GE) junction) or at the top of the esophagus, which allowed the pig to swallow the plasmid/liposome complex thereby coating the entire esophagus. An endoscope was placed 10 cm from the GE junction after injection of Photofrin and MnSOD-PL, a laser was inserted through the endoscope, then 400 Joules of light was delivered to the esophagus. PDT treatment was repeated 48 hours later. Control pigs were treated as above with no injection of MnSOD-PL. Pigs were followed for the development of esophageal stricture by weekly endoscopic exam and were weighed every two days. Esophageal biopsies were collected at various times following PDT. RNA was extracted and quantitative real time PCR was performed to determine gene expression for inflammatory cytokines including TNF-a and TGF-β. At 14 days after PDT treatment, control pigs lost significant weight and esophageal stricture was detected by endoscopic exam. By 20 days after PDT treatment, control pigs had severe esophageal stricture determined by endoscopy, weight loss, and barium swallow. Esophageal stricture in control PDT-treated pigs was documented by histopathology. In contrast, pigs intraesophageally treated with MnSOD-PL 24 hours before PDT had no weight loss, showed continual weight gain through 150 days after PDT and no esophageal stricture was detected by endoscopic exam. At 150 days after treatment, all MnSOD-PL-treated pigs were sacrificed, esophagus examined, and no stricture was detected. Thus, increased expression of MnSOD-PL may protect normal esophagus from PDT-induced stricture.

Overexpression of Manganese Superoxide Dismutase Prevents Photodynamic Therapy-Induced Porcine Esophageal Stricture

cells with calcein-AM labeled neuroblastoma cells for 6 hr and then measuring residual fluorescence (viable cells). Twelve cell lines were highly sensitive (5–16% viable cells), 4 were intermediate (30–37%), and 5 were relatively insensitive (42–96%) to direct NK cytotoxicity. Sensitivity was independent of resistance to cytotoxic chemotherapy, MYCN amplification, p53 function, and MHC class I expression. Neuroblastoma expression of ligands for NKG2D (MICA, MICB, ULBP-1, -2, -3; Taqman PCR) correlated with A-NK cytotoxicity (P 1⁄4 0.018). Flow cytometry confirmed that 4 cell lines expressed 2–3 ligands and that 8 others expressed ULBP-3. MAb M580 against NKG2D blocked cytotoxicity against LA-N-1 neuroblastoma cells. Anti-GD2 immunocytokine hu14.18/IL-2 was used to determine if cell lines with intermediate or low sensitivity were less able to trigger A-NK cells or were inherently resistant. A-NK killing was significantly increased against all lines by hu14.18/IL-2. Neuroblastomas forming in NOD/SCID mice after IV injection of luciferase transfected CHLA-255 (CHLA-255-luc) cells were revealed by Xenogen imaging. Adoptive transfer of A-NK cells by IV injection 7 and 8 days after giving CHLA-255-luc cells, especially in combination with hu14.18/IL-2, significantly delayed time to tumor detection in 3 or more sites (NK vs. control P 1⁄4 0.035; NK + hu14.18/IL-2 vs. control P , 0.001). Tumor burden in these groups, as quantified by total body Xenogen imaging on day 36, also differed (NK vs. control P 1⁄4 0.014; NK + hu14.18/IL-2 vs. control P , 0.001). We conclude that drug resistance does not affect NK activity against neuroblastoma cells and that cytotoxicity against some is NKG2D dependent. Furthermore, an anti-GD2/IL-2 immunocytokine significantly increases cytotoxicity in vitro and inhibits tumor formation in vivo. These data suggest that efficient targeting of A-NK cells to neuroblastoma sites may contribute to therapy of this disease.

An animal model of photodynamic-therapy-induced esophageal stricture: preliminary report

Photodynamic Therapy (PDT) using Photofrin has been recently approved by the FDA for the treatment of esophageal cancer and Barretts esophagus. A major limitation of PDT for Barretts esophagus is the development of esophageal stricture in up to 53% of patients. Mechanisms of PDT stricture formation have not been elucidated. The major difficulty is the lack of an animal model for PDT-induced stricture. We have used a pig model in which the esophagus is very similar to that of the human esophagus. Two (Scrofa) domestic pigs were injected with Photofrin at dosage of 2 mg/kg 48 hours prior to photoactivation with 630 nm light. Following anesthesia, a laser probe (2.5 cm in length) was passed through the oral cavity to approximately the mid-point of the esophagus via an endoscope. Light energy (400 Joules (J)/cm) was delivered as a single dose in one pig or repeated at 72 hours in the second pig. In this pig model, upper endoscopy, Barium swallow and pathological studies confirmed stricture formation following esophageal PDT exposure of 400 J as one or two fractions. We believe that this is the first animal model created to study esophageal strictures resulting from PDT.

Toxic pulmonary effects of photodynamic therapy (PDT) in a mouse model

A major limitation of PDT for Barretts esophagus is the development of esophageal strictures. This report summarizes the effects of PDT delivered to mouse esophagus. Sixty-two C3H/Nsd mice were injected with Photofrin (2-10mg/Kg) intraperitoneally. Forty-eight hours later a 1 cm laser probe was passed orally to the mid-esophagus. Light energy (630nm) ranged from 0 to 400 Joules/cm (J). Animals were sacrificed if death was imminent, otherwise at 6 weeks and 3 months. Gross and microscopic exams were performed on paraffin embedded esophagus and lung specimens. Exposure to 400J as a single fraction, 125 X 3 or 150 X 3 fractions resulted in a lethal pulmonary injury in 90% of mice within 48 hours. There was no esophageal mucosal damage at this early time point. Lower doses caused minor pulmonary injury allowing long-term survival but no change in the esophageal endothelium and no stricture. In the mouse, this histopathologic study demonstrates that pulmonary toxicity is the limiting factor following esophageal PDT. At lower PDT doses, minimal pulmonary damage occurred but no effect was observed on the esophagus. We believe the 5 mm depth of PDT injury leads to lethal pulmonary damage preventing subsequent study of the effects on the esophagus.