Positron emission tomography with f18-fluorodeoxyglucose in the staging and preoperative evaluation of malignant pleural mesothelioma

AbstractObjectives: The purpose of this study was to evaluate the utility of positron emission tomography with F18-fluorodeoxyglucose in the preoperative evaluation and staging of malignant mesothelioma in patients who were candidates for aggressive combined modality therapy. Methods: Eighteen consecutive patients with biopsy-proven malignant mesothelioma underwent positron emission tomographic scanning. The results of positron emission tomographic imaging were compared with results obtained by computed tomography, mediastinoscopy, thoracoscopy, and pathologic examination of surgical specimens. All patients fasted and received an average of 14.5 ± 2.7 mCi of F18-fluorodeoxyglucose for positron emission tomographic scanning. Attenuation-corrected whole-body and regional emission images of the chest and upper abdomen were acquired and formatted into transaxial, coronal, and sagittal images. Results: All primary malignant mesotheliomas accumulated F18-fluorodeoxyglucose, and the mean standardized uptake value was 7.6 (range, 3.33-14.85; n = 9). There were no false-negative results of positron emission tomography. Identification of occult extrathoracic metastases by positron emission tomography was the basis for excluding two patients from surgical therapy. There were two false-positive results of positron emission tomography: increased F18-fluorodeoxyglucose uptake in the contralateral chest that was negative by thoracoscopic biopsy (n = 1) and increased abdominal F18-fluorodeoxyglucose uptake after partial colectomy for diverticular disease (n = 1). Conclusions: Positron emission tomography can identify malignant pleural mesothelioma and appears to be a useful noninvasive staging modality for patients being considered for aggressive combined modality therapy. (J Thorac Cardiovasc Surg 2000;120:128-33

Technical Details of Laparoscopic Sleeve Gastrectomy Leading to Lowered Leak Rate: Discussion of 1070 Consecutive Cases

Laparoscopic sleeve gastrectomy is a widely utilized and effective surgical procedure for dramatic weight loss in obese patients. Leak at the sleeve staple line is the most serious complication of this procedure, occurring in 1-3% of cases. Techniques to minimize the risk of sleeve gastrectomy leaks have been published although no universally agreed upon set of techniques exists. This report describes a single-surgeon experience with an approach to sleeve leak prevention resulting in a progressive decrease in leak rate over 5 years. Methods. 1070 consecutive sleeve gastrectomy cases between 2012 and 2016 were reviewed retrospectively. Patient characteristics, sleeve leaks, and percent body weight loss at 6 months were reported for each year. Conceptual and technical changes aimed towards leak reduction are presented. Results. With the implementation of the described techniques of the sleeve gastrectomy, the rate of sleeve leaks fell from 4% in 2012 to 0% in 2015 and 2016 without a significant change in weight loss, as depicted by 6-month change in body weight and percent excess BMI lost. Conclusion. In this single-surgeon experience, sleeve gastrectomy leak rate has fallen to 0% since the implementation of specific technical modifications in the procedure

Hiatal Hernia Repair with Novel Biological Graft Reinforcement

Hiatal hernias are repaired laparoscopically with increasing use of reinforcement material. Both synthetic and biologically derived materials reduce the recurrence rate compared to primary crural repair. Synthetic mesh introduces complications, such as mesh erosion, fibrosis, and infection. Urinary bladder matrix (UBM) represents a biologically derived material for use in hiatal hernia repair reinforcement with the potential to improve durability of repair without incurring the risks of other reinforcement materials. Methods: The 15 cases presented involved hiatal hernia repair with primary crural repair with UBM reinforcement and fundoplication. Patients were followed for an average of 3 years, and were assessed with upper gastrointestinal (GI) series, endoscopy, and assessments of subjective symptoms of gastroesophageal reflux disease (GERD). Results: Hernia diameters averaged 6 cm. Each repair was successful and completed laparoscopically. UBM exhibited favorable handling characteristics when placed as a horseshoe-type graft sutured to the crura. One patient underwent endoscopic balloon dilatation of a mild postoperative stenosis that resolved. No other complications occurred. In more than 3 years of follow-up, there have been no recurrences or long-term complications. GERD-health-related quality of life (HRQL) scores averaged 6 (range, 0-12, of a possible 50), indicating little reflux symptomatology. Follow-up upper GI series were obtained in 9 cases and showed intact repairs. An upper endoscopy was performed in 8 patients and showed no recurrences. Conclusion: Surgeons may safely use laparoscopic fundoplication with UBM reinforcement for successful repair of hiatal hernias. In this series, repairs with UBM grafts have been durable at 3 years of follow-up and may serve as an alternative to synthetic mesh reinforcement of hiatal hernia repairs

Contractile Protein Expression and Phosphorylation and Contractility of Gastric Smooth Muscles from Obese Patients and Patients with Obesity and Diabetes

Ingested food is received, mixed, and ground into chyme by distinct gastric motility patterns. Diabetes impairs gastric muscle function, but the mechanisms underlying diabetes-induced gastric muscle dysfunction are unknown. Here, we compared the expression and phosphorylation of Ca2+ sensitization and contractile proteins in human gastric muscles from obese nondiabetic and diabetic patients. We also compared the spontaneous phasic contractions and the contractile responses evoked by electrical field stimulation of cholinergic motor neurons. Fundus and antrum muscles were obtained from sleeve gastrectomies and were used in in vitro myobath contractile studies and for capillary electrophoresis and immunodetection of γ-actin, CPI-17, pT38-CPI-17, MYPT1, pT853-MYPT1, pT696-MYPT1, myosin light chain (MYL9), pS19-MYL9, myosin light chain kinase (MYLK), protein phosphatase-1δ (PP1δ), and Rho-associated kinase (ROCK2). In diabetic fundus muscles, MYLK, ROCK2, and PP1δ expression was unchanged; MYPT1 and CPI-17 expression was decreased; and the pT853/MYPT1 and pT38/CPI-17 ratios, but not the pT696/MYPT1 ratio, were increased. Although MYL9 expression was increased, the pS19/MYL9 ratio was unchanged in diabetic fundus muscles. In diabetic antrum muscles, MYLK and MYL9 expression was unchanged, but ROCK2, CPI-17, and PP1δ expression was decreased. The pT38/CPI-17 ratio was unchanged, while the pS19/MYL9, pT853/MYPT1, and pT696/MYPT1 ratios were decreased, consistent with the reduced ROCK2 expression. The frequencies of spontaneous phasic contractions from nondiabetic and diabetic gastric fundus and antrum muscles did not significantly differ from each other, regardless of age, sex, or diabetic status. The fold increases in the contractions of diabetic fundus and antrum muscles in response to increased frequencies of electrical field stimulation were significantly lower compared to nondiabetic fundus and antrum muscles. The altered contractile responses and the protein expression and phosphorylation in gastric muscles of obese patients with diabetes illustrate the importance of understanding how smooth muscle Ca2+ sensitization mechanisms contribute to gastric motility

Contractile Protein Expression and Phosphorylation and Contractility of Gastric Smooth Muscles from Obese Patients an Patients with Obesity and Diabetes

Ingested food is received, mixed, and ground into chyme by distinct gastric motility patterns. Diabetes impairs gastric muscle function, but the mechanisms underlying diabetes-induced gastric muscle dysfunction are unknown. Here, we compared the expression and phosphorylation of Ca2+ sensitization and contractile proteins in human gastric muscles from obese nondiabetic and diabetic patients. We also compared the spontaneous phasic contractions and the contractile responses evoked by electrical field stimulation of cholinergic motor neurons. Fundus and antrum muscles were obtained from sleeve gastrectomies and were used in in vitro myobath contractile studies and for capillary electrophoresis and immunodetection of gamma-actin, CPI-17, pT38-CPI-17, MYPT1, pT853-MYPT1, pT696-MYPT1, myosin light chain (MYL9), pS19-MYL9, myosin light chain kinase (MYLK), protein phosphatase-1 delta (PP1 delta), and Rho-associated kinase (ROCK2). In diabetic fundus muscles, MYLK, ROCK2, and PP1 delta expression was unchangedMYPT1 and CPI-17 expression was decreasedand the pT853/MYPT1 and pT38/CPI-17 ratios, but not the pT696/MYPT1 ratio, were increased. Although MYL9 expression was increased, the pS19/MYL9 ratio was unchanged in diabetic fundus muscles. In diabetic antrum muscles, MYLK and MYL9 expression was unchanged, but ROCK2, CPI-17, and PP1 delta expression was decreased. The pT38/CPI-17 ratio was unchanged, while the pS19/MYL9, pT853/MYPT1, and pT696/MYPT1 ratios were decreased, consistent with the reduced ROCK2 expression. The frequencies of spontaneous phasic contractions from nondiabetic and diabetic gastric fundus and antrum muscles did not significantly differ from each other, regardless of age, sex, or diabetic status. The fold increases in the contractions of diabetic fundus and antrum muscles in response to increased frequencies of electrical field stimulation were significantly lower compared to nondiabetic fundus and antrum muscles. The altered contractile responses and the protein expression and phosphorylation in gastric muscles of obese patients with diabetes illustrate the importance of understanding how smooth muscle Ca2+ sensitization mechanisms contribute to gastric motility

DNA methylation, through DNMT1, has an essential role in the development of gastrointestinal smooth muscle cells and disease

DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMCs) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMCs are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency. Dnmt1-KO pups are born smaller than their wildtype littermates, have shortened GI tracts, and lose peristaltic movement due to loss of the tunica muscularis in their intestine, causing massive intestinal dilation, and death around postnatal day 21. Within smooth muscle tissue, significant CpG hypomethylation occurs across the genome at promoters, introns, and exons. Additionally, there is a marked loss of differentiated SMC markers (Srf, Myh11, miR-133, miR-143/145), an increase in pro-apoptotic markers (Nr4a1, Gadd45g), loss of cellular connectivity, and an accumulation of coated vesicles within SMC. Interestingly, we observed consistent abnormal expression patterns of enzymes involved in DNA methylation between both Dnmt1-KO mice and diseased human GI tissue. These data demonstrate that DNA hypomethylation in embryonic SMC, via congenital Dnmt1 deficiency, contributes to massive dysregulation of gene expression and is lethal to GI-SMC. These results suggest that Dnmt1 has a necessary role in the embryonic, primary development process of SMC with consistent patterns being found in human GI diseased tissue