Devi Mukkai Krishnamurty

Long-term randomized controlled trial of a novel nanopowder hemostatic agent (TC-325) for control of severe arterial upper gastrointestinal bleeding in a porcine model

BACKGROUND AND STUDY AIM Endoscopic therapy of brisk upper gastrointestinal bleeding remains challenging. A proprietary nanopowder (TC-325) has been proven to be effective in high pressure bleeding from external wounds. The efficacy and safety of TC-325 were assessed in a survival gastrointestinal bleeding animal model. METHOD 10 animals were randomized to treatment or sham. All animals received intravenous antibiotics, H2-blockers and heparin (activated clotting time 2 × normal). In a sterile laparotomy the gastroepiploic vessels were dissected, inserted through a 1-cm gastrotomy, and freely exposed in the gastric lumen, and the exposed vessel lacerated by needle knife. The treatment group received TC-325 by a modified delivery catheter while the sham group received no endoscopic treatment. Time to hemostasis, and mortality at 60 minutes, 24 hours, 48 hours, and 7 days were noted. Necropsy was performed in all animals. RESULTS Spurting arterial bleeding was achieved in all animals. No control animal showed hemostasis within the first hour compared with 100 % (5 / 5) in the treatment arm (mean 13.8 minutes, P < 0.0079). Durable hemostasis was achieved with no evidence of rebleeding after 1 and 24 hours in 80 % (4 / 5) of the treated animals compared with none in the control group ( P < 0.0098). None of the control animals survived more than 6 hours. Necropsy at 1 week in treated animals revealed healed gastrotomy without foreign body granuloma or embolization to the lung or brain. CONCLUSION TC-325 is safe and highly effective in achieving hemostasis in an anticoagulated severe arterial gastrointestinal bleeding animal model.

Gastric wall healing after NOTES procedures: closure with endoscopic clips provides superior histological outcome compared with threaded tags closure

BACKGROUND Closure of the transgastric access to the peritoneal cavity is a critical step in natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE To perform a direct comparison of the histological healing post clips and threaded tags (T-tags) closure after transgastric NOTES procedures. SETTING DESIGN AND INTERVENTION Twelve survival porcine experiments. After standardized endoscopic gastric wall puncture, balloon-dilation, and transgastric peritoneoscopy, closure of the gastric wall was performed with either clips or T-tags. Necropsy at 14 days was performed for histological evaluation of 2-mm interval transversal cross sections of the gastrotomy site. MAIN OUTCOME MEASUREMENTS Histological healing of the gastric wall opening. RESULTS Endoscopic closure of the gastrotomy was successfully achieved in all 12 animals, followed by an uneventful 2-week clinical follow-up. Transmural healing was seen in 3 (75%) animals after clip closure compared with only 1 (12.5%) in the group with T-tag closure (P = .06). Gastric wall muscular bridging was observed in 4 (100%) animals with clip closure compared with only 1 (12.5%) in the group with T-tag closure (P = .01). LIMITATIONS Animal model with short-term follow-up. CONCLUSIONS Endoscopic clip closure results in a layer-to-layer transmural healing of the gastric wall. In contrast, T-tag gastric wall plication impairs gastric layer bridging. These findings might guide the future design of new endoscopic devices and techniques for gastrotomy closure after NOTES procedures.

Adhesion formation after peritoneoscopy with liver biopsy in a survival porcine model: comparison of laparotomy, laparoscopy, and transgastric natural orifice transluminal endoscopic surgery (NOTES)

BACKGROUND AND STUDY AIMS Minimizing the invasiveness of operations by using natural orifice transluminal endoscopic surgery (NOTES) may reduce adhesion formation. The aim of the study was to compare rates of adhesion formation after peritoneoscopy with liver biopsy by laparotomy, laparoscopy, and transgastric NOTES. MATERIALS AND METHODS Experimental comparative survival study, at a university hospital. using 18 female pigs weighing 35 - 40 kg. Peritoneoscopy with liver biopsy was randomized to one of three groups: laparotomy, laparoscopy, and transgastric NOTES. Preoperative, operative, and postoperative care was standardized. Main outcome measures were: (i) survival and complication rates; (ii) assessment of adhesion formation using the Hopkins Adhesion Formation Score at necropsy (day 14). RESULTS 100 % of pigs with laparotomy and 33.3 % with laparoscopy had adhesions compared with 16.7 % who underwent transgastric NOTES. Documented adhesion bands totals for each group were: transgastric NOTES 1; laparoscopy 4; laparotomy 17. Median adhesion formation scores were: laparotomy 2.5 (range 2 - 4), compared with laparoscopy 0.0 (0 - 2), and transgastric NOTES 0.0 (0 - 1) ( P < 0.001). Spearman coefficient analysis revealed that correlation between adhesion scores assigned by two investigators was excellent (r = 0.99, P < 0.001, 95 % confidence interval [CI] 0.9978 - 0.9996). CONCLUSIONS Although this was a short-term study, with a low number of animals, it showed that transgastric NOTES and laparoscopy are associated with statistically significantly lower rates of adhesion formation than open surgery when peritoneoscopy with liver biopsy is performed. Incidence and severity of adhesions were lowest with transgastric NOTES.

Salivary duct carcinoma responding to trastuzumab-based therapy: case report and review of the literature.

Salivary duct carcinoma (SDC) is a rare malignancy with a poor prognosis. Human epidermal growth factor receptor‐2 (Her‐2/neu) is overexpressed in SDC and, hence, HER‐2/neu targeted therapy could be an option.

Hydrogen leak test is minimally invasive and highly specific for assessment of the integrity of the luminal closure after natural orifice transluminal endoscopic surgery procedures (with video).

BACKGROUND Leak-resistant closure of transluminal access is a major challenge facing natural orifice transluminal endoscopic surgery (NOTES). OBJECTIVE To evaluate a hydrogen (H(2))-based leak test for assessment of transluminal-access closure integrity after NOTES procedures. SETTING Nine acute porcine experiments. DESIGN AND INTERVENTION After gastric-wall puncture and balloon dilation, peritoneoscopy was performed, followed by transmural closure of the gastric opening. The animals were randomly assigned to complete or incomplete closure groups. The H(2) leak test was performed by using 1000 mL of 4% H(2) gas mixture and the Hydrogen Leak Detector H2000+. The animals were then euthanized for a methylene blue (MB) test of gastric closure integrity. MAIN OUTCOME MEASUREMENT Intraperitoneal H(2) concentration after gastric insufflation with H(2). RESULTS The H(2) leak test was quick and easy. Intraperitoneal H(2) concentrations in parts per million in both groups were similar at baseline (mean +/- SD, 0.18 +/- 0.29 parts per million [ppm] vs 0.22 +/- 0.35 ppm, P = .97) and after balloon dilation (414.8 +/- 198.5 ppm vs 601.3 +/- 116.1 ppm, P > .99). Postclosure intraperitoneal H(2) concentrations dropped to 0.01 +/- 0.77 ppm in the complete-closure group, similar (P = .81) to matched-pairs preopening levels and significantly lower than in the incomplete-closure group (162.0 +/- 83.0 ppm, P < .02). On necropsy, the MB test was negative in all 5 animals of the complete-closure group and positive in all 4 animals of the incomplete-closure group. A cutoff of 25 ppm in intraperitoneal H(2) concentration after closure gave 100% sensitivity, specificity, and positive and negative predictive values for MB leakage. LIMITATIONS Nonsurvival animal experiments. CONCLUSIONS The H(2) leak test is highly accurate for detection of leakage after NOTES procedures and could become a substitute for currently used MB leak tests.

Importance of surgical margins in rectal cancer

Distal resection margin (DRM) and circumferential resection margin (CRM) are two important considerations in rectal cancer management. Although guidelines recommend a 2 cm DRM, studies have shown that a shorter DRM is adequate, especially in patients receiving neoadjuvant chemoradiation. Standardization of total mesorectal excision has greatly improved quality of CRM. Although more patients are undergoing sphincter‐saving procedures, abdominoperineal resection is indicated for very distal tumors, and pelvic exenteration is often necessary for tumors involving pelvic organs. J. Surg. Oncol. 2016;113:323–332.

Autoimmune pancreatitis: current diagnostic criteria are suboptimal.

Background and Aims:  The preoperative diagnosis of autoimmune pancreatitis (AIP) is difficult, given its similar clinical presentation to pancreatic cancer. The aims of the study are to describe our centers experience with AIP and apply the Japanese AIP diagnostic criteria to a cohort of patients with histologically‐proven AIP in order to assess their performance characteristics.

Epidemiology and Discrimination in Obesity

Obesity is a growing epidemic, with 33 % of the world’s population being overweight or obese. The epidemic is posing great economic and social challenges to many countries and is already a major political factor. Through a comprehensive review of the literature and global statistics, we describe the obesity epidemic, the dynamics responsible, and the associated disparities and discrimination. Only through a better understanding of the scope and forces behind this global health burden can we better guide the necessary prevention and treatment.

S2014 Age and Multifocality of Cystic Lesions Are Associated with Increased Risk of Carcinoma in Situ or Invasive Pancreatic Adenocarcinoma in Patients with High Risk Family History

min) groups and tumor volumes were measured in every 4 days. Metformin (given intraperitoneally, once/day, 250 mg/kg, for 25-41 days), significantly decreased (p<0.005) the growth of MiaPaca-2 and Panc-1 xenografts. At the end of the experiments the MiaPaCa-2 xenograft tumor volumes were 1075 ± 207mm3 (control) and 414 ± 116mm3 (metformin), and in the Panc-1 xenografts 1198 ± 134 mm3(control) and 412 ±122 mm3 (metformin). Conclusion: Metformin significantly inhibits the growth of pancreatic cancer cells In Vitro and in subcutaneous xenografts in mice. Thus, metformin could be a potential candidate in novel strategies for treatment of human pancreatic cancer.