Antitumor activity of paclitaxel is significantly enhanced by a novel proapoptotic agent in non-small cell lung cancer.

BACKGROUND: Newer targeted agents are increasingly used in combination chemotherapy regimens with enhanced survival and improved toxicity profile. Taxols, such as paclitaxel, independently potentiate tumor destruction via apoptosis and are used as first line therapy in patients with advanced non-small cell lung cancer (NSCLC). Procaspase-3-activating compound-1 (PAC-1) is a novel proapoptotic agent that directly activates procaspase-3 (PC-3) to caspase-3, leading to apoptosis in human lung adenocarcinoma cells. Hence, we sought to evaluate the antitumor effects of paclitaxel in combination with PAC-1. METHODS: Human NSCLC cell lines (A-549 and H-322m) were incubated in the presence of PAC-1 and paclitaxel. Tumor cell viability was determined by a tetrazolium-based colorimetric assay (MTT assay). Western blot and flow cytometric analysis were performed to evaluate expression of PC-3 and the proportion of apoptotic cells, respectively. A xenograft murine model of NSCLC was used to study the in vivo antitumor effects of PAC-1. RESULTS: PAC-1 significantly reduced the inhibitory concentration 50% of paclitaxel from 35.3 to 0.33 nM in A-549 and 8.2 to 1.16 nM in H-322m cell lines. Similarly, the apoptotic activity significantly increased to 85.38% and 70.36% in A-549 and H322m, respectively. Significantly enhanced conversion of PC-3 to caspase-3 was observed with PAC-1 paclitaxel combination (P < 0.05). Mice treated with a drug combination demonstrated 60% reduced tumor growth rate compared with those of controls (P < 0.05). CONCLUSIONS: PAC-1 significantly enhances the antitumor activity of paclitaxel against NSCLC. The activation of PC-3 and thus the apoptotic pathway is a potential strategy in the treatment of human lung cancer.

The effect of metallic tracheal stents on radiation dose in the airway and surrounding tissues.

BACKGROUND: Metallic airway stents are often used in the management of central airway malignancies. The presence of a metallic foreign body may affect radiation dose in tissue. We studied the effect of a metallic airway stent on radiation dose delivery in a phantom and an in vivo porcine model. METHODS: A metallic tracheal stent was fitted onto a support in a water phantom. Point dosimeters were positioned in the phantom around the support and the stent. Irradiation was then performed on a linear accelerator with and without the stent. Metallic tracheal stents were deployed in the trachea of three pigs. Dosimeters were implanted in the tissues near (Group 1) and away (Group 2) from the stent. The pigs were then irradiated, and the dose perturbation factor was calculated by comparing the actual dose detected by the dosimeters versus the planned dose. RESULTS: The difference in the dose detected by the dosimeters and the planned dose ranged from 1.8% to 6.1% for the phantom with the stent and 0%-5.3% for the phantom without the stent. These values were largely within the manufacturer's specified error of 5%. No significant difference was observed in the dose perturbation factor for Group 1 and Group 2 dosimeters (0.836 ± 0.058 versus 0.877 ± 0.088, P = 0.220) in all the three pigs. CONCLUSIONS: Metallic airway stents do not significantly affect radiation dose in the airway and surrounding tissues in a phantom and porcine model. Radiation treatment planning systems can account for the presence of the stent. External beam radiation can be delivered without concern for significant dose perturbation.

The incidence of trocar-site hernia in minimally invasive bariatric surgery: a comparison of multi versus single-port laparoscopy.

INTRODUCTION: Single-port laparoscopy (SPL) employs a 1.5- to 2.5-cm incision at the umbilicus for the placement of a single working port. We hypothesized that the longer incision created by SPL compared with multiport laparoscopy may increase the incidence of trocar-site hernias. We examined our experience with SPL in bariatric operations. METHODS: There were 734 laparoscopic sleeve gastrectomy and laparoscopic adjustable gastric banding procedures performed at our institution between 2001 and 2011. Fifty-eight patients were lost to follow-up or had a short duration of follow-up (<1 month). Of the remaining 676 cases, 163 were performed via SPL. All laparoscopic wounds created by trocar size greater than 12 mm were closed with absorbable suture. RESULTS: Patient demographics of the SPL group and the multiport group were similar in terms of age, gender, and comorbidities. The average body mass index (BMI) of the SPL group was lower than the multiport group (43.5 ± 5.3 vs. 45.8 ± 7.7, p < 0.01). The mean follow-up for the SPL group was 11 months versus 24 months for the multiport group. There were three trocar-site hernias out of 513 cases in the multiport compared to one hernia out of 163 cases in the SPL group (0.6 vs. 0.6 %, p = 0.967). All trocar-site hernias occurred at the 15-mm port site. The median time to hernia occurrence for the multiport group was 13 months (range, 1-18). In the SPL group, the hernia occurred at 8 months. On multivariate analysis, age, BMI, SPL, procedure type, and the postoperative weight loss were not associated with the development of trocar-site hernias. CONCLUSIONS: SPL did not increase the rate of trocar-site hernia in this series. A low rate of trocar-site hernia can be achieved with the use of SPL in bariatric surgery.

Laparoscopic-facilitated endoscopic submucosal dissection, mucosal resection, and partial circumferential ("wedge") colon wall resection for benign colorectal neoplasms that come to surgery.

BACKGROUND: Large polyps that come to surgery are removed via colectomy (CR). Alternatives are MIS-facilitated endoscopic submucosal dissection/endoscopic mucosal resection (ESD/EMR) or wedge resection (WR). This study presents the results of 26 polyp patients who had minimally invasive surgery (MIS)-monitored ESD/EMR, WR, or if necessary, standard CR. METHODS: The authors used a retrospective review of 1 surgeon's experience. ESD/EMR was the first choice, WR was the second, and CR was the last resort. RESULTS: Polyp locations were as follows: right/transverse, 16 (62%); rectum, 7 (27%); and left/sigmoid, 3 (12%). ESD/EMR was successful in 13 patients and WR in 4; 9 patients required CR. Median flatus times were as follows: ESD/EMR, 1 day; WR, 2 days; and CR, 3 days (ESD/EMR vs CR, P = .01). Median length of stay was as follows: ESD/EMR, 3 days; WR, 5 days; and CR, 5 days (ESD/EMR vs CR, P = .0037). There were no leaks or abscesses. Carcinoma was found in 3 patients. Postoperatively, 2 ESD/EMR patients had residual polyp fully removed via a scope. CONCLUSIONS: ESD/EMR and WR appear to be safe but techniques are evolving. Larger studies are needed.

Wernicke Encephalopathy After Bariatric Surgery: a Literature Review.

Wernicke encephalopathy (WE) is an acute neurological disorder classically characterized by ataxia, ophthalmoplegia, and altered mental status. This is caused by thiamine deficiency and is usually seen in malnourished populations. However, with the advent and rise of bariatric surgery in the last 50 years, WE has become an increasingly recognized and potentially deadly complication. Here, we review the populations at risk, clinical presentation, and the incidence of WE in the bariatric surgery population from 1985 to 2023. While the predominant procedure shifts throughout the years, the overall incidence of WE per 100,000 cases for the following procedures are sleeve gastrectomy (1.06), gastric band (1.16), RYGB (4.29), and biliopancreatic diversion with duodenal switch (8.92). Thus, early intervention and post-operative supplementation is recommended to prevent WE.

Duodenal Adenocarcinoma in the Setting of Bariatric Surgery: A Perfect Storm for Wernicke's Encephalopathy.

Wernicke's encephalopathy (WE) is a condition resulting from thiamine deficiency that typically presents with acute neurologic symptoms including ataxia, eye movement disorders, and altered mental status. Though classically seen in patients with alcohol use disorder, it can also occur as a complication of bariatric surgery and gastrointestinal cancers. Here, we present a patient with a history of gastric band surgery and an intact alimentary tract. She presented with acute, intractable vomiting and epigastric abdominal pain, incompletely relieved by deflating her gastric band, and was found to have duodenal adenocarcinoma causing partial duodenal obstruction. She was then found to have binocular diplopia, horizontal nystagmus, dizziness, reduced proprioception, and pins-and-needles numbness in her bilateral lower extremities, and there was concern for gait instability; thus, WE was suspected. The patient was treated with high-dose thiamine repletion, and her symptoms resolved shortly thereafter. WE is rare in patients who have undergone gastric band surgery, and to our knowledge, this is the first case of WE in a patient with concurrent duodenal adenocarcinoma. This case illustrates that patients with a history of bariatric surgery may be more susceptible to developing WE in the face of a new gastrointestinal insult, such as duodenal cancer.

Effects of gastrogastric fistula repair on weight loss and gut hormone levels.

BACKGROUND: Weight regain after gastric bypass (GBP) can be associated with a gastrogastric fistula (GGF), in which a channel forms between the gastric pouch and gastric remnant, allowing nutrients to pass through the "old route" rather than bypassing the duodenum. To further understand the mechanisms by which GGF may lead to weight regain, we investigated gut hormone levels in GBP patients with a GGF, before and after repair. MATERIALS AND METHODS: Seven post-GBP subjects diagnosed with GGF were studied before and 4 months after GGF repair. Another cohort of 22 GBP control subjects without GGF complication were studied before and 1 year post-GBP. All subjects underwent a 50-g oral glucose tolerance test and blood was collected from 0-120 min for glucose, insulin, ghrelin, PYY3-36, GIP, and GLP-1 levels. RESULTS: Four months after GGF repair subjects lost 6.0 ± 3.9 kg and had significantly increased postprandial PYY3-36 levels. After GGF repair, fasting and postprandial ghrelin levels decreased and were strongly correlated with weight loss. The insulin response to glucose also tended to be increased after GGF repair, however no concomitant increase in GLP-1 was observed. Compared to the post-GBP group, GLP-1 and PYY3-36 levels were significantly lower before GGF repair; however, after GGF repair, PYY3-36 levels were no longer lower than the post-GBP group. CONCLUSIONS: These data utilize the GGF model to highlight the possible role of duodenal shunting as a mechanism of sustained weight loss after GBP, and lend support to the potential link between blunted satiety peptide release and weight regain.

Laparoendoscopic single-site surgery for the placement of an adjustable gastric band: a large cohort comparison.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery has been shown to be a well-tolerated alternative for the placement of an adjustable gastric band. To date, only small series have suggested that this approach may provide potential clinical benefits over standard multiport laparoscopy. The objective of this study was to compare the outcomes of patients undergoing LESS adjustable gastric banding (LESS-AGB) and a cohort of patients undergoing standard multiport laparoscopic adjustable gastric banding (LAGB). METHODS: A total of 206 patients underwent placement of an adjustable gastric band. Of these, 106 patients underwent LESS-AGB and were compared with a demographically similar cohort of 100 patients who underwent standard LAGB. Data collected included operative time, parenteral and oral narcotic consumption, duration of patient controlled analgesia (PCA) device, subjective pain scores using the 0-10 numeric pain intensity scale, and length of stay. Unpaired t test was used for analysis. RESULTS: Compared with multiport LAGB patients, LESS-AGB patients reported significantly less pain at the first postoperative hour (P = .012), twelfth postoperative hour (P = .017), and twenty-fourth postoperative hour (P = .012), and consumed fewer oral analgesic tablets (P = .012). Operative times were significantly longer in the LESS-AGB group (P = .029). No significant differences were seen in duration of PCA, parenteral narcotic consumption, or length of stay. One LESS-AGB case required conversion to multiport laparoscopy. Complication rates were similar between the 2 groups. CONCLUSION: LESS-AGB is associated with less pain and less oral analgesic consumption than multiport LAGB. Given these clinical advantages and superior cosmetic results, laparoendoscopic single-site surgery may be an attractive alternative approach for patients considering LAGB.

Single port sleeve gastrectomy: strategic use of technology to re-establish fundamental tenets of multiport laparoscopy.

BACKGROUND: Laparoscopic sleeve gastrectomy is commonly performed using multiple ports. The quest to minimize surgical trauma has led to the development of single port laparoscopy, which has been shown to be a safe, less-invasive method of performing a variety of abdominal surgeries. We describe the feasibility and safety of single port sleeve gastrectomy (SPSG) for morbid obesity at an academic affiliate of a university hospital. METHODS: A total of 25 patients undergoing elective SPSG were compared with a demographically similar contemporaneous cohort of 9 patients who underwent standard multiple port laparoscopic sleeve gastrectomy. The data collected included the operative time, narcotic consumption, duration of patient controlled analgesia use, subjective pain scores, and length of stay. RESULTS: The patients undergoing SPSG experienced significantly less pain at 1 hour postoperatively (P = .039). No statistically significant difference was found in pain between the 2 groups at 12 and 24 hours (P = .519 and P = .403, respectively). The quantity of narcotic use (P = .538), duration of patient controlled analgesia use (P = .820), and length of stay (P = .571) were not significantly different between the 2 groups. The operative time for SPSG was 118 minutes versus 101 minutes for multiple port surgery (P = .160). CONCLUSIONS: SPSG is safe and feasible for selected patients. The patients undergoing SPSG reported significantly less pain at the first postoperative hour. No significant differences between the 2 groups were seen in any of the other postoperative parameters.

Outcomes of laparoscopic Roux-en-Y gastric bypass versus laparoscopic adjustable gastric banding in adolescents.

BACKGROUND: The goal of this study is to compare the outcomes of laparoscopic adjustable gastric banding (LAGB) and laparoscopic Roux-en-Y gastric bypass (LRYGB) in obese adolescents. METHODS: We performed a retrospective review of all adolescents between the ages of 15 and 19 who underwent LAGB or LRYGB at our university affiliated Bariatric Center of Excellence from 2002 to 2011. Postsurgical weight loss at 1, 3, 6, 12, 18, and 24 months was noted and expressed as percentage of excess weight loss (% EWL). RESULTS: Thirty-two patients underwent LRYGB and 23 underwent LAGB. The LAGB group was younger (18.6 ± 0.6 versus 17.2 ± 1.5) than the LRYGB group. Other preoperative demographic factors including body mass index, gender, ethnicity, and comorbidities were similar between the two groups. The average % EWL was superior in the LRYGB group compared to the LAGB group at all time points studied (p < 0.05), although at 2-year follow-up, only 16% (5/32) LRYGB and 30% (7/23) LAGB patients were available for follow-up. Three patients with type II diabetes mellitus underwent LRYGB and all experienced remission of their diabetes. The number of complications requiring interventions was similar between the two groups. CONCLUSIONS: In our study, adolescents undergoing LRYGB achieved superior weight loss compared to LAGB in the short-term follow-up. The complication rate for LAGB was similar compared to LRYGB. More studies are needed to monitor the long-term effects of these operations on adolescents before definitive recommendations can be made.