Synthesis of androstanopyridine and pyrimidine compounds as novel activators of the tumor suppressor protein p53.

A series of androstane derivatives 2-16 were synthesized from 3ß-hydroxyandrostan-17-one derivatives (1a-e). Compounds (1a,b) were treated with ethyl cyanoacetate, cyanoacetamide, or malononitrile and gave the corresponding derivatives 2-7, respectively. Additionally, compounds (1a-e) were condensed with cyanothioacetamide, urea, or guanidine hydrochloride afforded the corresponding derivatives 8-12, which then by Moffat oxidation gave the oxidized derivatives 9, 11 and 13, respectively. Finally, compound (1) condensed with acetyl acetone or ethyl acetoacetate gave cyclohexene derivatives (14a-c) and (15a,b), respectively. Compound 15 was oxidized with a Moffat oxidizing agent and afforded the corresponding oxidized compound 16. The newly synthesized compounds activated the tumor suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2.

Single-incision laparoscopic cholecystectomy for biliary dyskinesia in children: a simple, safe, and inexpensive technique.

PURPOSE: To evaluate a low-cost technique for single-incision laparoscopic cholecystectomy (SILC) in children with biliary dyskinesia. PATIENTS AND METHODS: Eighteen children with biliary dyskinesia underwent SILC between March and September 2010. Two 5-mm trocars and a directly introduced grasper were inserted through a 2-cm vertical transumbilical incision. Instrument collisions were minimized by using low-profile trocars and a bariatric laparoscope with a right-angle light adaptor. An internally anchored retracting device suspended the gallbladder, obviating the need for an additional trocar. No other special equipment was used. RESULTS: There were 15 girls and 3 boys with a mean age of 15.9 years (range, 9-18 years). Sixteen (88.9%) underwent true SILC. One patient was converted to a four-port laparoscopic procedure because of uncertainty of ductal anatomy. Another required a 5-mm subxiphoid port for liver retraction. Mean operative time was 82 minutes (range, 42-105 minutes): 94 minutes (range, 75-105 minutes) for the first 6 patients, 85 minutes (range, 60-102 minutes) for the second 6, and 68 minutes (range, 42-90 minutes) for the last 6. Operative times between the first and last groups were significantly different (P=.02). Sixteen patients were discharged home the following day and the remaining 2 on the second postoperative day. There were no complications. The hospital costs of the disposable equipment needed to perform SILC at our institution was $205.05 less than that needed for the four-port operation ($516.32 versus $721.37), a 28.4% savings. CONCLUSIONS: SILC is safe and feasible in children with biliary dyskinesia. The operative time decreased with experience. The disposable equipment needed was less expensive than that used for the standard laparoscopic technique.

Three trocar laparoscopic Roux-en-y gastric bypass: a novel technique en route to the single-incision laparoscopic approach.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass is the gold standard bariatric procedure. Typically, the procedure necessitates five to seven small skin incisions for trocar placement. The senior author (AA Saber) has developed a three-trocar approach for laparoscopic Roux-en-Y gastric bypass. METHODS: Sixteen patients underwent triple-incision laparoscopic Roux-en-Y gastric bypass between May 2009 and August 2009. The same surgeon performed all surgical interventions. The umbilicus was the main point of entry for all patients and the same operative technique and perioperative protocol were used in all patients. RESULTS: A total of sixteen triple-incision laparoscopic Roux-en-Y gastric bypasses were performed. The procedures were successfully performed in all patients. Mean operating time was 145.4 min. None of the patients required conversion to an open procedure. There were no mortalities or post-operative technical complications noted during the immediate post-operative period. CONCLUSION: Three trocar laparoscopic Roux-en-Y gastric bypass is safe, technically feasible and reproducible. This technique may be considered a "precursor" to single-incision laparoscopic Roux-en-Y gastric bypass.

Simple technique for single incision transumbilical laparoscopic appendectomy.

INTRODUCTION: Acute appendicitis is one of the most commonly encountered surgical problems in everyday practice. With the recent increase in popularity of single incision laparoscopic surgery (SILS), several techniques for SILS appendectomy have already been described. We herein describe our own simplified technique for single incision transumbilical laparoscopic appendectomy. MATERIALS AND METHODS: From December 2008 to August 2009, a total of 26 patients consented for single incision laparoscopic appendectomy for acute appendicitis. Preoperative, intraoperative and postoperative data were collected. RESULTS: Our technique was successful in 19 out of 26 (73.1%) patients, while seven patients required the placement of additional trocars. None of the patients needed conversion to an open approach. Mean OR time was 45.9 min. The mean length of stay was 1.1 day. Only one patient had developed postoperative umbilical wound infection. CONCLUSION: Our technique for single incision laparoscopic transumbilical appendectomy is safe feasible, and reproducible. Prospective randomized studies comparing the single incision laparoscopic approach with its conventional multiport counterpart are necessary to confirm the conclusions of our early experience.

Early experience with lidocaine patch for postoperative pain control after laparoscopic ventral hernia repair.

INTRODUCTION: Reduced postoperative pain is one of the many factors that have driven the growing emphasis on the role of laparoscopic surgery for surgical management. Several studies have documented the advantages of the laparoscopic repair of ventral hernias compared to the open ventral herniorraphy. However, the laparoscopic approach may be associated with more postoperative pain initially. In this preliminary study, we present data from our early experience with the use of a lidocaine patch for pain control in the immediate postoperative period following laparoscopic ventral hernia repair (LVH). METHODS: Thirty consecutive patients underwent laparoscopic ventral herniorraphy (LVH) and were selected randomly and placed into one of two groups. In one group, we placed a lidocaine patch (LP) (Lidoderm, Endo Pharmaceuticals, Inc., Chadds Ford, PA) on the anterior abdominal wall corresponding to the placement site of the underlying mesh in fifteen patients (Group A). In the second group, we did not place a LP on the abdominal wall of fifteen consecutive patients (Group B). We assessed all patients according to their demographic data, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) score, the size of the abdominal wall defect (AWD), area of mesh (size) used, operative time, length of hospital stay (LOA), morbidity, and the individual patient's pain score at discharge, two weeks and two months postoperatively. RESULTS: The two groups were similar with respect to demographics, BMI, ASA, AWD, size of mesh, LOS and morbidity. Group A had a statistically significant reduction in their postoperative pain score at discharge when compared to Group B (3.13+/-1.68 and 4.8+/-1.42, respectively, p value=0.0067). CONCLUSION: In this preliminary study, the use of a lidocaine patch in the management of postoperative pain following laparoscopic ventral herniorraphy is a safe and promising modality to consider in the management of postoperative pain control.

Single incision laparoscopic sleeve gastrectomy (SILS): a novel technique.

BACKGROUND: Laparoscopic sleeve gastrectomy is an emerging bariatric procedure that typically necessitates five to seven small skin incisions to place five to seven trocars. The senior author (Saber) has developed a single umbilical incision approach to laparoscopic sleeve gastrectomy. METHODS: Seven patients underwent single access transumbilical laparoscopic sleeve gastrectomy between March 2008 and July 2008. The same surgeon performed all surgical interventions. The umbilicus was the sole point of entry for all patients, and the same operative technique and perioperative protocol were used in all patients. RESULTS: A total of seven single-incision laparoscopic sleeve gastrectomies were performed. The procedure was successfully performed in all patients. Mean operating time was 125 min. None of the patients required conversion to an open procedure. There were no mortalities or postoperative complications noted during the mean follow-up period of 3.4 months. CONCLUSION: Single-incision transumbilical laparoscopic sleeve gastrectomy is safe, technically feasible, and reproducible.

Simplified laparoscopic parastomal hernia repair: the scroll technique.

BACKGROUND: Laparoscopic parastomal hernia repair can be technically challenging. We herein present a simplified technique of laparoscopic parastomal hernia repair. METHODS: This technique entails fixation of the rolled mesh to the anterior abdominal wall before unfolding it, each side of the mesh is unfolded and fixed individually using transfascial sutures and tacks. RESULTS: This technique was used in 3 patients; The average time for mesh placement was about 30 minutes. The mean length of stay was 2 days. Apart from 1 patient who developed a transient postoperative seroma, there were no intraoperative or postoperative complications. CONCLUSIONS: This technique of mesh placement minimizes intracorporeal mesh manipulation, facilitates fixation of the mesh to the anterior abdominal wall, and provides adequate coverage to the hernia defect while hosting the colostomy without restriction.

The effect of laparoscopic Roux-en-Y gastric bypass on fibromyalgia.

BACKGROUND: Fibromyalgia is a chronic debilitating disorder affecting 3-5% of the US population. Treatment of this disorder is a challenge. The incidental finding of improvement of fibromyalgia following laparoscopic Roux-en-Y gastric bypass stimulated us to study this phenomenon. METHODS: A retrospective chart review of patients with fibromyalgia who underwent laparoscopic Roux-en-Y gastric bypass. RESULTS: Postoperative decrease in median of BMI from 49.4 to 29.7 was significant (p value = 0.0010). This was associated with statistically significant improvement in median of pain score (p value = 0.0010) and median points of tenderness (p value = 0.0010). CONCLUSION: Significant weight loss following laparoscopic Roux-en-Y gastric bypass is associated with resolution or improvement of fibromyalgia. Consequently, the bariatric surgeon should be a member of the multidisciplinary team approach for treating fibromyalgia.

Advanced age: is it an indication or contraindication for laparoscopic ventral hernia repair?

INTRODUCTION: Ventral hernias are common surgical problems in the geriatric population. Although ventral hernias are electively repaired in younger patients, the safety and efficacy of elective laparoscopic hernia repair in the geriatric age group is not well documented in the literature. METHODS: A review of 155 patients undergoing laparoscopic ventral hernia repair was undertaken. The patients were classified according to their age into 2 groups, Group A (n=126) for those who are 65 years old. The patient demographics, comorbidities, hernia characteristics, and operative and postoperative data were compared. RESULTS: Younger patients were found to have a significantly increased BMI, while the older group had an increased number of comorbidities. No difference was found in the complication or recurrence rates between the 2 groups. CONCLUSION: Elective laparoscopic ventral hernia repair in senior citizens is safe and feasible in our experience. We believe that the decision to perform an elective hernia repair in this patient population should be based on the general condition of the patient rather than the patient's chronological age.

Early experience with intraluminal reinforcement of stapled gastrojejunostomy during laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: The use of extraluminal staple-line buttressing material during laparoscopic Roux-en-y gastric bypass has shown the potential to reduce staple-line leak and bleeding. We herein present our early experience with intraluminal reinforcement of linear-cutting stapled gastrojejunal anastomosis with the use of bioabsorbable glycolide copolymer staple-line reinforcement. METHODS: Laparoscopic Roux-en-Y gastric bypass was performed in 80 consecutive non-randomized morbidly obese patients. Gastrojejunal anastomosis was performed using a linear-cutting stapler without staple-line reinforcement in 40 patients (group A), while in the other 40 patients (group B), gastrojejunostomy was performed using a linear cutting stapler with intraluminal reinforcement material (bioabsorbable glycolide copolymer). Demographic data were collected. The rate of gastrojejunal anastomotic leak, bleeding, and stricture was determined. RESULTS: There was a statistically significant reduction in bleeding complications between the two groups (15% bleeding in group A vs. no bleeding in group B, P value=0.0255). Stricture rate was higher in-group A (10% group A vs. 2.5% in group B); however, the difference was not statistically significant (P value=0.2007). None of our patients developed a gastrojejunal leak. CONCLUSION: Intraluminal reinforcement of gastrojejunal anastomosis during laparoscopic gastric bypass is safe and feasible. The use of intraluminal bioabsorbable glycolide copolymer staple-line reinforcement significantly reduces the incidence of gastrojejunal bleeding.

Laparoscopic spigelian hernia repair: the scroll technique.

Spigelian hernia is a rare clinical entity. It has a subtle clinical presentation with vague abdominal pain that may warrant laparoscopy. Even though laparoscopic ventral hernia repair is increasingly popular, laparoscopic repair of spigelian hernia has not been adequately studied. Eight patients who underwent laparoscopic spigelian hernia repair are presented herein, along with a description of our simple technique for mesh placement. In addition, literature review of laparoscopic repair of spigelian hernia is also presented. Our case series included six females and two males; two patients presented acutely whereas the others presented with chronic pain. Laparoscopic repair was successfully performed in all of our patients with a mean operative time of 92.5 minutes. There were no postoperative complications or recurrence with a mean follow up of 36 months. Our scroll technique for laparoscopic repair is simple and feasible. It minimizes intracorporeal mesh manipulation, facilitates mesh fixation to the anterior abdominal wall, and maintains a precise orientation of the mesh in relation to the defect.

Occult ventral hernia defects: a common finding during laparoscopic ventral hernia repair.

BACKGROUND: In many incidences, laparoscopic exploration reveals occult ventral hernia defects that were not detected on physical examination. The objective of this study was to describe the frequency of occult ventral hernia defects detected during laparoscopy. METHODS: Prospectively collected data on 146 consecutive patients who underwent laparoscopic ventral hernia repair were reviewed. The numbers of ventral defects found on preoperative physical examination were compared with those found during the laparoscopic procedure. RESULTS: Out of 146 laparoscopic ventral hernia repair patients, 70 patients (48%) were found to have occult defects that were not detected on preoperative abdominal examination. Among all the possible variables, only the type of hernia was found to have a significant difference. CONCLUSION: Almost half of the patients with a ventral hernia have clinically occult hernia defects that can be recognized laparoscopically. This indicates the importance of careful inspection of the anterior abdominal wall during the surgical procedure.

Bariatric surgery: the past, present, and future.

BACKGROUND: Our objective is to review the history and development of different procedures of bariatric surgery, along with a summary of the most commonly performed bariatric procedures today and a look on the future trends in the field of bariatric surgery. METHODS: Review of the available English language literature concerning bariatric surgery. RESULTS: The literature review included articles that have information about the history of bariatric surgery, different techniques used for each procedure, and the outcome of each procedure. CONCLUSIONS: Bariatric surgery is a dynamic field. Experts are continuously searching for an ideal, minimally invasive procedure that is both safe and effective.