Poly(I:C) source, molecular weight and endotoxin contamination affect dam and prenatal outcomes, implications for models of maternal immune activation.

The viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) is increasingly used to induce maternal immune activation (mIA) to model neurodevelopmental disorders (NDDs). Robust and reproducible phenotypes across studies are essential for the generation of models that will enhance our understanding of NDDs and enable the development of improved therapeutic strategies. However, differences in mIA-induced phenotypes using poly(I:C) have been widely observed, and this has prompted the reporting of useful and much needed methodological guidelines. Here, we perform a detailed investigation of molecular weight and endotoxin variations in poly(I:C) procured from two of the most commonly used suppliers, Sigma and InvivoGen. We demonstrate that endotoxin contamination and molecular weight differences in poly(I:C) composition lead to considerable variability in maternal IL-6 response in rats treated on gestational day (GD)15 and impact on fetal outcomes. Specifically, both endotoxin contamination and molecular weight predicted reductions in litter size on GD21. Further, molecular weight predicted a reduction in placental weight at GD21. While fetal body weight at GD21 was not affected by poly(I:C) treatment, male fetal brain weight was significantly reduced by poly(I:C), dependent on supplier. Our data are in agreement with recent reports of the importance of poly(I:C) molecular weight, and extend this work to demonstrate a key role of endotoxin on relevant phenotypic outcomes. We recommend that the source and batch numbers of poly(I:C) used should always be stated and that molecular weight variability and endotoxin contamination should be minimised for more robust mIA modelling.

Dietary gap assessment: an approach for evaluating whether a country's food supply can support healthy diets at the population level.

OBJECTIVE: Dietary diversity, and in particular consumption of nutrient-rich foods including fruits, vegetables, nuts, beans and animal-source foods, is linked to greater nutrient adequacy. We developed a 'dietary gap assessment' to evaluate the degree to which a nation's food supply could support healthy diets at the population level. Design/Setting In the absence of global food-based dietary guidelines, we selected the Dietary Approaches to Stop Hypertension (DASH) diet as an example because there is evidence it prevents diet-related chronic disease and supports adequate micronutrient intakes. We used the DASH guidelines to shape a hypothetical 'healthy' diet for the test country of Cameroon. Food availability was estimated using FAO Food Balance Sheet data on country-level food supply. For each of the seven food groups in the 'healthy' diet, we calculated the difference between the estimated national supply (in kcal, edible portion only) and the target amounts. RESULTS: In Cameroon, dairy and other animal-source foods were not adequately available to meet healthy diet recommendations: the deficit was -365 kcal (-1527 kJ)/capita per d for dairy products and -185 kcal (-774 kJ)/capita per d for meat, poultry, fish and eggs. Adequacy of fruits and vegetables depended on food group categorization. When tubers and plantains were categorized as vegetables and fruits, respectively, supply nearly met recommendations. Categorizing tubers and plantains as starchy staples resulted in pronounced supply shortfalls: -109 kcal (-457 kJ)/capita per d for fruits and -94 kcal (-393 kJ)/capita per d for vegetables. CONCLUSIONS: The dietary gap assessment illustrates an approach for better understanding how food supply patterns need to change to achieve healthier dietary patterns.

Laparoscopic repair of complex ventral hernia facilitated by pre-operative chemical component relaxation using Botulinum Toxin A.

PURPOSE: The operative management of complex ventral hernia poses a formidable challenge, despite recent advances in surgical techniques. Recurrence rates after complex ventral hernia repair remain high, and increase with each failed attempt. This study examines the effect of pre-operative abdominal wall chemical component relaxation using Botulinum Toxin A (BTA) to induce temporary flaccid paralysis in order to facilitate laparoscopic repair of large complex ventral hernia. METHODS: This is a prospective evaluation of 27 patients from January 2013 to August 2015 who underwent ultrasound guided BTA injections to the lateral abdominal wall muscles prior to elective complex ventral hernia repair. Non-contrast serial CT imaging was obtained pre- and post-BTA injection to measure change in fascial defect size and abdominal wall muscle thickness and length. Fascial defects were closed and hernias repaired using laparoscopic or laparoscopic-assisted intra-peritoneal onlay mesh (IPOM) techniques. RESULTS: 27 patients received pre-operative BTA injections which were well tolerated with no complications. Comparison of pre-BTA and post-BTA CT imaging demonstrated a significant increase in mean length of the lateral abdominal wall from 15.7 cm pre-BTA to 19.9 cm post-BTA (p < 0.0001), with mean unstretched length gain of 4.2 cm/side (range 0-11.7 cm/side). All hernias were surgically reduced and repaired with mesh, with no early recurrences. CONCLUSION: Pre-operative administration of BTA is a safe and effective technique in the pre-operative preparation of patients undergoing elective complex ventral hernia repair. This technique lengthens and relaxes the laterally retracted abdominal muscles and enables laparoscopic closure of large complex ventral hernia.

Urologic complications in renal transplant recipients by donor type.

BACKGROUND AND PURPOSE: Reduced donor morbidity has been established after laparoscopic donor nephrectomy compared with open harvest, but differences in recipient outcomes remain less obvious. We compared the urologic complications in patients receiving kidneys procured by cadaveric, open, and laparoscopic harvest. PATIENTS AND METHODS: A retrospective study of all the kidney transplantations performed between January 1998 and December 2003 was undertaken to extract 100 consecutive patients in each group. All urologic complications were obtained and grouped by the type of donor procurement. RESULTS: Overall, 48 of the 276 transplant patients (17%) had urologic complications: 14% of the cadaveric-donor recipients, 20% of the open-donor recipients, and 18% of the laparoscopic-donor recipients. There were no ureteral complications in the laparoscopic group. CONCLUSIONS: Laparoscopically procured donor kidneys were associated with significantly fewer recipient ureteral complications than open cadaver or live-donor procurement.

Intraoperative cholangiography is still indicated after preoperative endoscopic cholangiography for gallstone disease.

BACKGROUND: Intraoperative cholangiography (IOC) is frequently omitted in patients undergoing laparoscopic cholecystectomy (LC) if they have had successful preoperative endoscopic retrograde cholangiography (ERC). METHODS: A prospectively maintained divisional laparoscopic cholecystectomy database was searched from 1991 to 1997 for patients who had IOC after preoperative ERC. The presence of recurrent or residual common duct stones seen on IOC and their impact on subsequent management were evaluated. RESULTS: We identified a group of 127 patients who underwent preoperative ERC. Thirty-one patients (31/127, or 24%) went on to receive an IOC during cholecystectomy. In 15 patients whose preoperative ERC was reported normal, five (33%) had an abnormal IOC. In 16 patients whose ERC was reported as having cleared the duct, eight (50%) had an IOC abnormality. Eight of these 31 patients required a further procedure to clear the duct. CONCLUSION: Retained or recurrent common duct stones at cholecystectomy following diagnostic or therapeutic ERC were more common than expected. Therefore, IOC is recommended during LC regardless of the findings yielded by the preoperative ERC.

Hand-assisted laparoscopic surgery: an emerging technique.

BACKGROUND: Some surgeons are finding that the placement of one hand in the abdomen during laparoscopic procedures returns tactile feedback lost during purely laparoscopic surgery and facilitates dissection, retraction, and control of bleeding. Studies comparing patient postoperative discomfort after laparoscopic and hand-assisted laparoscopic procedures have not found a significant difference. METHODS: This article is a review of the current literature on hand-assisted laparoscopic surgery and of the different hand-assisted devices on the market. Included in the review are opinions of expert laparoscopic surgeons who have used hand-assisted devices. RESULTS: More than 100 hand-assisted laparoscopic procedures have been described in the literature. At least four different companies are involved in hand-assisted laparoscopic devices. Three of these companies currently are Food and Drug Administration (FDA) approved in the United States. CONCLUSIONS: Hand-assisted laparoscopic surgery is not necessary for all laparoscopic procedures. Hand-assisted laparoscopic technique is advantageous for certain procedures and clinical situations such as en bloc resections and removal of solid organ tumors, large colon tumors, and the kidney after donor nephrectomy. This technique offers benefits when a large incision is necessary to complete surgery such an open colon anastomosis.

Laparoscopic pancreatic resection: single-institution experience of 19 patients.

BACKGROUND: The number of laparoscopic pancreatic resections reported in the surgical literature has been remarkably low. Few substantive data are available concerning current indications and outcomes after laparoscopic pancreatectomy. The purpose of this article is to review the recent indications, complications, and outcomes after laparoscopic pancreatic resection. STUDY DESIGN: A retrospective analysis of the Mount Sinai hospital records was performed for all patients who underwent laparoscopic distal pancreatectomy or enucleation between the time of the first resection in November 1993 until the time of this study in March 2000. RESULTS: In the 19 patients (6 men) the mean age was 53 years (range 22 to 83 years). In 16 patients (84%) the entire procedure was done by laparoscopy; one operation was converted to a hand-assisted technique; and two cases were converted to open. Median operating time was 4.4 hours (range 1.6 to 6.6 hours), and median intraoperative blood loss was 200 mL. Postoperative complications included three pancreatic leaks (16%), one case of superficial phlebitis, and one prolonged ileus for 7 days (total morbidity of 26%). There were no deaths. The median length of postoperative hospital stay was 6 days (range 1 to 26 days). CONCLUSIONS: This represents the largest single-institution experience with laparoscopic pancreatic resection. The considerable morbidity rate is comparable to recently published open series, and is likely inherent in pancreatic surgery, rather than the technical approach. Laparoscopic pancreatic surgery resulted in shorter hospital stays and appears to be safe for benign diseases.

Diagnostic and interventional laparoscopy and intraoperative ultrasonography in the management of pancreatic disease.

The laparoscopic management of pancreatic disorders has evolved dramatically from its inception in 1911 and its rediscovery in the 1970s. Although investigators once proclaimed that "it seems unlikely that laparoscopy will have any more than an extremely limited use in the investigation of pancreatic disorders," laparoscopy and LUS now have a well-recognized role in the staging of pancreatic cancer and an increasing part in the management of benign pancreatic disease at many institutions. Although the appropriate role of LS and LUS is debatable, the development and refinement of laparoscopic techniques and instrumentation and the improvement of noninvasive diagnostic modalities will provide new data, increase the rate of resection at laparotomy, and allow surgeons to treat a broader range of pancreatic disease by minimally invasive methods. The value of LS and LUS for benign and malignant pancreatic disorders has been clearly demonstrated, but the inevitable issues of hospital resource, operative expertise, and surgical philosophy will ultimately determine the role of laparoscopy and LUS in clinical practice.

Are concerns over right laparoscopic donor nephrectomy unwarranted?

OBJECTIVE: To examine the ability of several large, experienced transplantation centers to perform right-sided laparoscopic donor nephrectomy safely with equivalent long-term renal allograft function. SUMMARY BACKGROUND DATA: Early reports noted a higher incidence of renal vein thrombosis and eventual graft loss. However, exclusion of right-sided donors would deprive a significant proportion of donors a laparoscopically harvested graft. METHODS: A retrospective review was performed among 97 patients from seven centers performing right-sided laparoscopic donor nephrectomy. Surgical and postoperative demographic factors were evaluated. Complications were identified and long-term renal allograft function was compared with historical left-sided laparoscopic donor nephrectomy cohorts. RESULTS: Right laparoscopic donor nephrectomy was performed for varying reasons, including multiple left renal arteries or veins, smaller right kidney, or cystic right renal mass. Mean surgical time was 235.0 +/- 66.7 minutes, with a mean blood loss of 139 +/- 165.8 mL. Conversion was required in three patients secondary to bleeding or anatomical anomalies. Mean warm ischemic time was limited at 238 +/- 112 seconds. Return to diet was achieved on average after 7.5 +/- 2.3 hours, with mean discharge at 54.6 +/- 22.8 hours. Two grafts were lost during the early experience of these centers to renal vein thrombosis. Both surgical and postoperative complications were limited, with few long-term adverse effects. Mean serum creatinine levels were higher than open and left laparoscopic donor nephrectomy on postoperative day 1, but at all remaining intervals the right laparoscopic donors had equivalent creatinine values. CONCLUSIONS: These results confirm that right laparoscopic donor nephrectomy provides similar patient benefits, including early return to diet and discharge. Long-term creatinine values were no higher than in traditional open donor or left laparoscopic donor cohorts. These results establish that early concerns about high thrombosis rates are not supported by a multiinstitutional review of laparoscopic right donor nephrectomies.

[Laparoscopic nephrectomy in the liver donor: introduction of the method and preliminary results]. / Néphrectomie par laparoscopie chez le donneur vivant: introduction de la méthode et résultats préliminaires.

INTRODUCTION: The shortage of organs available for renal transplantation has focussed attention on the use of live donors. Techniques for laparoscopic nephrectomy have recently been described, which have limited morbidity, duration of hospitalization and the period off work. However, these surgical procedures are difficult, and may be risky for the organ to be transplanted. METHOD: The laparoscopic live donor nephrectomy was introduced in stages, including the use of a videoconference from a reference center. In this article, the prospective analysis of the present authors' preliminary results has been presented. RESULTS: Ten kidneys were removed by laparoscopy, i.e., three from the left and seven from the right side. No conversion of this technique to laparotomy was necessary. The mean warm ischemic time was five minutes, and in the last six operations it did not exceed three minutes. The patients were able to leave hospital between four and eight days following surgery. After a mean follow-up of 10.5 months, organ survival was 100%, and in all grafts excellent function was observed. CONCLUSION: The quality of these preliminary results which may act as a reference and the careful introduction of a live donor laparoscopic program could provide an incentive to potential donors, and thereby increase the pool of organs available for transplantation.

Laparoscopically assisted intestinal resection in 88 patients with Crohn's disease.

BACKGROUND: Experience with 94 resections in 88 patients with Crohn's disease using advanced laparoscopic techniques is reported. Records of patients who underwent intestinal resection for Crohn's disease between August, 1993 and November, 1998 were reviewed. Indications, operative findings, clinicopathologic, and postoperative data were recorded. METHODS: In this study, the mean age was 37 years (range, 16-70 years), and 55% of the participants were women. Indications for surgery included obstruction (64 cases), pain (22 cases), peritonitis (1 case) and abscess (1 case). Seventy patients underwent ileocolic resection, 28 of whom had a previous history of one or two ileocolic resections. Eight of these patients had additional procedures including tubal ligation (1), sigmoidectomy (1), cholecystectomy (3 cases), and enterectomy (3 cases). Small bowel resection (13 cases), right hemicolectomy (3 cases), subtotal colectomy (3 cases), anterior rectal resection (2 cases), and sigmoid resection (3 cases) were performed in the remaining patients. All but one procedure were completed laparoscopically with extracorporeal anastomosis. The average length of intestine resected was 33 cm (range, 10-92 cm). Forty-one patients had 58 fistulae between ileum, jejunum, mesentery, colon, abdominal wall, skin, or bladder. Mean blood loss was 168 ml (range, 30-800 ml) and mean operative time was 183 min (range, 96-400 min). RESULTS: More than 85% of the patients were tolerating a liquid diet on the first postoperative day. Average length of hospital stay was 4.2 days (range, 3-11 days). Complications included anastomotic leak necessitating reoperation, stricture requiring endoscopic dilation, hemorrhage treated expectantly, urinary tract infection, pulmonary embolus, line sepsis, and early postoperative intestinal obstruction (7 cases) requiring reoperation in three cases. CONCLUSIONS: Experience with both advanced laparoscopic techniques and conventional surgery for inflammatory bowel disease allowed successful laparoscopic management of patients with complicated Crohn's disease.

Durability of laparoscopic repair of paraesophageal hernia.

OBJECTIVES: To define a method of primary repair that would minimize hernia recurrence and to report medium-term follow-up of patients who underwent laparoscopic repair of paraesophageal hernia to verify durability of the repair and to assess the effect of inclusion of an antireflux procedure. SUMMARY BACKGROUND DATA: Primary paraesophageal hernia repair was completed laparoscopically in 55 patients. There were five recurrences within 6 months when the sac was not excised (20%). After institution of a technique of total sac excision in 30 subsequent repairs, no early recurrences were observed. METHODS: Inclusion of an antireflux procedure, incidence of subsequent hernia recurrence, dysphagia, and gastroesophageal reflux symptoms were recorded in clinical follow-up of patients who underwent a laparoscopic procedure. RESULTS: Mean length of follow-up was 29 months. Forty-nine patients were available for follow-up, and one patient had died of lung cancer. Mean age at surgery was 68 years. The surgical morbidity rate in elderly patients was no greater than in younger patients. Eleven patients (22%) had symptoms of mild to moderate reflux, and 15 were taking acid-reduction medication for a variety of dyspeptic complaints. All but 2 of these 15 had undergone 360 degrees fundoplication at initial repair. Two patients (4%) had late recurrent hernia, each small, demonstrated by esophagram or endoscopy. CONCLUSIONS: Laparoscopic repair in the medium term appeared durable. The incidence of postsurgical reflux symptoms was unrelated to inclusion of an antireflux procedure. In the absence of motility data, partial fundoplication was preferred, although dysphagia after floppy 360 degrees wrap was rare. With the low morbidity rate of this procedure, correction of symptomatic paraesophageal hernia appears indicated in patients regardless of age.

Sac excision is essential to adequate laparoscopic repair of paraesophageal hernia.

BACKGROUND: We compared the incidence of early hernia recurrence in nonrandomized but consecutive patients undergoing laparoscopic repair of paraesophageal hernia (LRPH) without and with excision of the hernia sac. METHODS: LRPH was completed in 55 of 58 patients. In the first 25 patients, the sac was not excised. Total sac excision was performed in the subsequent 30 patients. All patients had crural repair with or without fundoplication, or gastropexy. RESULTS: Mean age of patients was 68 years (range, 34-95). There were three conversions; one patient died postoperatively. Mean operative time was 225 min in the first group and 190 min in the sac excision group. Median length of stay was 2 days (range, 1-15) for both groups. CONCLUSIONS: A precise method of total sac excision simplified dissection. It also ensured complete reduction of the hernia and availability of adequate esophageal length. Operative time was not increased, and no subsequent early recurrences were observed (p < 0.05).

The difficult cholecystectomy: problems related to concomitant diseases.

The difficult gallbladder is the most common "difficult" laparoscopic surgery performed by general surgeons. It is also "potentially" the one that places the patient at significant risk. This article reports on our first 1,900 laparoscopic cholecystectomies. With this report, it is the desire of the authors to share our experiences and lessons learned from more than 300 difficult gallbladder cases. We surgeons must strive for no bile duct injuries. If certain principles are followed, the surgeon will be able to improve his or her completion rate and decrease (if not eliminate) bile duct injuries. First and foremost is to know when to convert to open. Performance of fluorocholangiography to define anatomy is also very helpful in avoidance of bile duct injury. The laparoscopic surgeon should start with simple cases before "graduating" to more complex cases. Lastly, the ability to suture and knot tie is key in performing advanced procedures. This skill will allow completion of cases that otherwise would have to be converted to traditional surgery.

The role of laparoscopy in the diagnosis and treatment of abdominal pain syndromes.

BACKGROUND: Diagnostic laparoscopy plays a significant role in the evaluation of acute and chronic abdominal pain in the era of therapeutic laparoscopic surgery. METHODS: We referred to our personal series of laparoscopy for both acute and chronic abdominal pain. This is a retrospective review of data accumulated prospectively between 1979 and the present. RESULTS: In our series, 387 consecutive patients underwent laparoscopy because of abdominal pain. In a group of 121 patients with acute abdominal pain, a definitive diagnosis was made in 119 cases (98%). Two patients needed laparotomy to confirm the diagnosis; both had a disease process that did not require laparotomy to treat. A definitive therapeutic laparoscopic procedure was performed in 53 cases 944%). In 45 patients (38%), a diagnosis was made that did not require therapeutic laparoscopy or laparotomy to treat. In the remaining 21 patients (17.5%), exploratory laparotomy was needed to treat the condition. In a chronic abdominal pain group of 265 patients, the etiology was established laparoscopically in 201 cases (76%). A definitive therapeutic laparoscopic procedure was performed in 128 patients (48%). There was a normal laparoscopic examination in 64 patients (24%). There was one false negative laparoscopy that required laparotomy to treat 1 month later. CONCLUSIONS: Laparoscopy is an accurate modality for the diagnosis of both acute and chronic abdominal pain syndromes. These data support the use of laparoscopy as the primary invasive intervention in patients with acute and chronic abdominal pain.

Current laparoscopic approaches to pancreatico-biliary disease.

Biliary-enteric anastomoses to duodenum or jejunum are a laparoscopic reality and will find a place in the management of complicated choledocholithiasis or malignant strictures of the bile duct. Staging by laparoscopy in pancreatic malignancy is an ideal strategy, with some operators able to complete a definitive laparoscopic palliative bypass in the same sitting. Intraoperative laparoscopic sonography is an advancing technique and has great potential in the evaluation of choledocholithiasis, hepatic metastases and staging of pancreatic cancer. Innovative options exist to deal with bile duct calculi, including antegrade sphincterotomy and intraoperative stent placement.

Laparoscopic surgery in Crohn's disease. Indications and results.

BACKGROUND: An effort was made to assess the feasibility, safety, and outcome of laparoscopic procedures performed in patients with Crohn's disease. METHODS: A prospectively maintained laparoscopic database was analyzed regarding operation time, intra- and postoperative complications, conversion to laparotomy, and length of hospitalization.Fifty-one patients (23 males and 28 females) with a mean age of 36 (20-79) years underwent a laparoscopic or laparoscopic-assisted procedure for Crohn's disease. The indications included terminal ileitis in 31 patients, colitis in 11, perianal disease in four, duodenal Crohn's disease in three, and rectovaginal and rectourethral fistula in one patient each. Thirty-two patients underwent an ileocolic resection; total abdominal colectomy with ileorectal anastomosis was performed in six patients with end ileostomy in one, take down of end ileostomy and ileorectal anastomosis in three, duodenal bypass gastrojejunostomy in three, and loop ileostomy in six patients. RESULTS: The mean operating time was 2.4 (0.6-4.5) h and the mean length of hospital stay was 5.1 (3-18) days. Eight complications were noted in seven patients (14%), which included enterotomy in two patients, bleeding in two, stoma obstruction in two, pelvic sepsis in one, and efferent limb obstruction in one. The procedure was converted to laparotomy in seven patients (14%) due to a large inflammatory mass in five and to bleeding in two patients; there was no mortality. CONCLUSION: Laparoscopic surgery is a feasible, versatile, and safe modality in the surgical management of Crohn's disease. Despite the often-malnourished state of these steroid-dependent patients with intraabdominal inflammatory conditions, morbidity, procedural length, and length-of-hospitalization data are all similar to results previously reported for less-challenging laparoscopic colorectal procedures.

Laparoscopic assisted colectomy.

BACKGROUND: The role and feasibility of laparoscopic assisted colectomy (LAC) in both benign and malignant disease of the colon are not clear. We have reviewed our series in an effort to further delineate whether or not LAC is appropriate in the treatment of colonic disease. METHODS: This is a retrospective view of a personal series focusing on feasibility, cure of malignant disease, and length of stay (LOS). RESULTS: One hundred and two LACs were completed out of 104 attempts (98%). There were no wound or trocar implants in the Dukes A, B and C patients. Lymph node retrieval was similar in the laparoscopic and open historical controls. The LOS was 5.9 days in the LAC group as compared with 11 days in the open group. There was a 4.8% major morbidity rate and a 1% mortality rate in this series. CONCLUSIONS: LAC is technically feasible in a high percentage of patients. While a definite statement regarding its use in malignant disease can not be ascertained from this review, the preliminary results are encouraging. A randomized trial comparing open and LAC is warranted.