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The main function of the stomach is to digest ingested food. Gastric antrum muscular contractions mix ingested food with digestive enzymes and stomach acid and propel the chyme through the pyloric sphincter at a rate in which the small intestine can process the chyme for optimal nutrient absorption. Mfge8 binding to α8β1 integrins helps regulate gastric emptying by reducing the force of antral smooth muscle contractions. The source of Mfge8 within gastric muscles is unclear. Since Mfge8 is a secreted protein, Mfge8 could be delivered via the circulation, or be locally secreted by cells within the muscle layers. In this study, we identify a source of Mfge8 within human gastric antrum muscles using spatial transcriptomic analysis. We show that Mfge8 is expressed in subpopulations of Mef2c+ perivascular cells within the submucosa layer of the gastric antrum. Mef2c is expressed in subpopulations of NG2+ and PDGFRB+ pericytes. Mfge8 is expressed in NG2+/Mef2c+ pericytes, but not in NG2+/Mef2c−, PDGFRB+/Mef2c−, or PDGFRB+/Mef2c+ pericytes. Mfge8 is absent from CD34+ endothelial cells but is expressed in a small population of perivascular ACTA2+ cells. We also show that α8 integrin is not expressed by interstitial cells of Cajal (ICC), supporting the findings that Mfge8 attenuates gastric antrum smooth muscle contractions by binding to α8β1 integrins on enteric smooth muscle cells. These findings suggest a novel, supplementary mechanism of regulation of gastric antrum motility by cellular regulators of capillary blood flow, in addition to the regulation of gastric antrum motility by the enteric nervous system and the SMC, ICC, and PDGFRα+ cell (SIP) syncytium.

L-type CaA multiscale approach including patch-clamp electrophysiology, super-resolution nanoscopy, proximity ligation assay, calcium imaging' pressure myography, and Laser Speckle imaging was implemented to examine CaCaThese results suggest that PKA-dependent S1928 phosphorylation promotes the spatial reorganization of vascular α1

The stomach acts as a buffer between the ingestion of food and its processing in the small intestine. It signals to the brain to modulate food intake and it in turn regulates the passage of a nutrient-rich fluid, containing partly digested food, into the duodenum. These processes need to be finely controlled, for example to restrict reflux into the esophagus and to transfer digesta to the duodenum at an appropriate rate. Thus, the efferent pathways that control gastric volume, gastric peristalsis and digestive juice production are critically important. We review these pathways with an emphasis on the identities of the final motor neurons and comparisons between species. The major types of motor neurons arising from gastric enteric ganglia are as follows: immunohistochemically distinguishable excitatory and inhibitory muscle motor neurons; four neuron types innervating mucosal effectors (parietal cells, chief cells, gastrin cells and somatostatin cells); and vasodilator neurons. Sympathetic efferent neurons innervate intramural arteries, myenteric ganglia and gastric muscle. Vagal efferent neurons with cell bodies in the brain stem do not directly innervate gastric effector tissues; they are pre-enteric neurons that innervate each type of gastric enteric motor neuron. The principal transmitters and co-transmitters of gastric motor neurons, as well as key immunohistochemical markers, are the same in rat, pig, human and other species.

The L-type Ca2+ channel CaV1.2 is essential for arterial myocyte excitability, gene expression and contraction. Elevations in extracellular glucose (hyperglycemia) potentiate vascular L-type Ca2+ channel via PKA, but the underlying mechanisms are unclear. Here, we find that cAMP synthesis in response to elevated glucose and the selective P2Y11 agonist NF546 is blocked by disruption of A-kinase anchoring protein 5 (AKAP5) function in arterial myocytes. Glucose and NF546-induced potentiation of L-type Ca2+ channels, vasoconstriction and decreased blood flow are prevented in AKAP5 null arterial myocytes/arteries. These responses are nucleated via the AKAP5-dependent clustering of P2Y11/ P2Y11-like receptors, AC5, PKA and CaV1.2 into nanocomplexes at the plasma membrane of human and mouse arterial myocytes. Hence, data reveal an AKAP5 signaling module that regulates L-type Ca2+ channel activity and vascular reactivity upon elevated glucose. This AKAP5-anchored nanocomplex may contribute to vascular complications during diabetic hyperglycemia., Molecular mechanisms by which glucose modulates L-type Ca2+ channel activity and vascular reactivity are unclear. Here the authors report a nanocomplex orchestrated by AKAP5 that facilitates local purinergic stimulation of L-type Ca2+ channels and vasoconstriction during diabetic hyperglycemia.

Previous research demonstrates that exposure to adverse childhood experiences (ACEs) is associated with development of obesity. The same mechanisms mediating this relationship could theoretically affect attempts to lose weight in adulthood. However, it is unclear whether or not exposure to ACEs impacts the effectiveness of bariatric surgery. The present study aimed to examine the association of exposure to ACEs to postoperative weight loss outcomes. One hundred ninety-eight patients undergoing bariatric surgery were evaluated for their exposure to ACEs, determined by a presurgical questionnaire and recorded as an ACEs score. Percent total weight loss (%TWL) was calculated to evaluate postoperative weight loss at 1-, 3-, and 6-month intervals postoperatively. One hundred forty-two participants were available for follow-up at the 6-month postoperative interval. The sample consisted of 167 women and 31 men with a mean age of 47.7. Twenty-five percent of participants experienced high exposure to ACEs, defined as experiencing ≥ 4 ACEs. The average %TWL at 6 months was 16.52%. Multilevel modeling found no significant relationship between ACEs score and %TWL at any of the postoperative time intervals, both before and after adjusting for age, sex, and race. High exposure to ACEs was not associated with poorer weight loss outcomes, and participants with a large number of ACEs generally lost the anticipated amount of weight.

Metalloendopeptidase ADAM-Like Decysin 1 (ADAMDEC1) is an anti-inflammatory peptidase that is almost exclusively expressed in the gastrointestinal (GI) tract. We have recently found abundant and selective expression of Adamdec1 in colonic mucosal PDGFRα

Gastric endocrine cell hormones contribute to the control of the stomach and to signalling to the brain. In other gut regions, enteroendocrine cells (EECs) exhibit extensive patterns of colocalisation of hormones. In the current study, we characterise EECs in the human gastric fundus and corpus. We utilise immunohistochemistry to investigate EECs with antibodies to ghrelin, serotonin (5-HT), somatostatin, peptide YY (PYY), glucagon-like peptide 1, calbindin, gastrin and pancreastatin, the latter as a marker of enterochromaffin-like (ECL) cells. EECs were mainly located in regions of the gastric glands populated by parietal cells. Gastrin cells were absent and PYY cells were very rare. Except for about 25% of 5-HT cells being a subpopulation of ECL cells marked by pancreastatin, colocalisation of hormones in gastric EECs was infrequent. Ghrelin cells were distributed throughout the fundus and corpus; most were basally located in the glands, often very close to parietal cells and were closed cells i.e., not in contact with the lumen. A small proportion had long processes located close to the base of the mucosal epithelium. The 5-HT cells were of at least three types: small, round, closed cells; cells with multiple, often very long, processes; and a subgroup of ECL cells. Processes were in contact with their surrounding cells, including parietal cells. Mast cells had very weak or no 5-HT immunoreactivity. Somatostatin cells were a closed type with long processes. In conclusion, four major chemically defined EEC types occurred in the human oxyntic mucosa. Within each group were cells with distinct morphologies and relationships to other mucosal cells.

Background Complex ventral incisional hernia repair represents a challenging clinical condition in which biologically derived graft reinforcement is often utilized, but little long-term data inform that decision. Urinary bladder matrix (UBM) has shown effectiveness in diverse clinical settings as durable reinforcement graft material, but it has not been studied over a long term in ventral incisional hernia repair. This study evaluates the clinical, radiographic, and histological outcome of complex incisional hernia repair using UBM reinforcement with 12–70 months of follow-up. Methods A single-arm, retrospective observational study of all ventral incisional hernia repairs utilizing UBM reinforcement over a 6-year time frame by a single surgeon was performed. Patients were assessed in long-term follow-up clinically and with the Carolina Comfort Scale. A subset of patients was assessed with abdominal wall ultrasound or CT scan. Three patients had abdominal wall fascial biopsies years after the incisional hernia repair with UBM graft, and the histology is analyzed. Results 64 patients underwent repair of complex incisional hernias with UBM graft reinforcement by a single surgeon. 42 patients had concomitant procedures including large or small bowel resection, excision of infected mesh, evacuation of abscess or hematoma, cholecystectomy, or panniculectomy with abdominoplasty. 16 patients had ostomies at the time of repair. Median follow-up time is 36 months, with a range of 12–70 months. Nine patients (14%) have required surgical repair of a recurrent hernia, and a tenth patient has a recurrence that is managed non-surgically, for a total recurrence rate of 15.6% over the entire time frame. Median time to recurrence was 32 months, and a Kaplan–Meier freedom from recurrence curve is depicted. 28 patients have undergone ultrasound or CT assessments of the abdominal wall which demonstrate radiographic fascial integrity 12–70 months after repair. Three patients have been re-explored for unrelated reasons in the years following ventral incisional hernia repair with UBM, and full thickness fascial biopsies demonstrate a robust remodeling response histologically similar to native myofascial tissue. No patients have developed graft infection, fistulization to the graft, or required graft explantation. Carolina Comfort Scale assessment of 45 patients 3 years after the repair averaged 16 out of a possible 115. Conclusion In 64 patients undergoing complex ventral incisional hernia repair with UBM reinforcement, all have experienced successful resolution of complex clinical conditions and 15.6% of these repairs have recurred at a median follow-up of 3 years. Three full-thickness biopsies of the repaired fascia years later shed light on a promising remodeling response which may signal strength and durability comparable to native fascia.

Elevated glucose increases vascular reactivity by promoting L-type CaV1.2 channel (LTCC) activity by protein kinase A (PKA). Yet, how glucose activates PKA is unknown. We hypothesized that a Gs-coupled P2Y receptor is an upstream activator of PKA mediating LTCC potentiation during diabetic hyperglycemia. Experiments in apyrase-treated cells suggested involvement of a P2Y receptor underlying the glucose effects on LTTCs. Using human tissue, expression for P2Y11, the only Gs-coupled P2Y receptor, was detected in nanometer proximity to CaV1.2 and PKA. FRET-based experiments revealed that the selective P2Y11 agonist NF546 and elevated glucose stimulate cAMP production resulting in enhanced PKA-dependent LTCC activity. These changes were blocked by the selective P2Y11 inhibitor NF340. Comparable results were observed in mouse tissue, suggesting that a P2Y11-like receptor is mediating the glucose response in these cells. These findings established a key role for P2Y11 in regulating PKA-dependent LTCC function and vascular reactivity during diabetic hyperglycemia.

Background There is no current consensus on the management of large hiatal hernias concomitant with performance of a sleeve gastrectomy procedure. Proposed solutions have included performing a modified Nissen fundoplication, performing cruroplasty alone, utilizing the Linx device, performing cruroplasty with reinforcement material, and avoiding the sleeve procedure altogether in favor of a bypass procedure in order to minimize gastroesophageal reflux. 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 This study reports the results of a retrospective chart review of 32 cases of large hiatal hernia repair utilizing both primary crural repair and UBM reinforcement concomitant with laparoscopic sleeve gastrectomy by a single surgeon. Hernia diameter averaged 6 cm (range 4-9 cm). After an average of 1 year followup, 30 patients were assessed for subjective symptoms of gastroesophageal reflux (GERD) using the Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score. Twenty patients were evaluated with either upper gastrointestinal (GI) series, endoscopy, or both. Results Each repair was successful and completed laparoscopically concomitant with sleeve gastrectomy. Anterior and posterior cruroplasty was performed using interrupted 0-Ethibond suture using the Endostitch device. The UBM graft exhibited favorable handling characteristics placed as a keyhole geometry sutured to the crura with absorbable suture. A careful chart review was undertaken to assess for complications. There have been no reoperations. After a median of 12 months (range, 4-27 months) of followup, an assessment of recurrences or long-term complications was completed. Median GERD-HRQL score was 6, with a range of 0 to 64 (of possible 75), indicating very low-level reflux symptomatology. Follow-up upper GI radiographs or endoscopy were obtained in 20 cases and show intact repairs. Conclusion In this series of 32 cases, laparoscopic cruroplasty with UBM graft reinforcement has been effective and durable at 12 months of followup. This technique may offer one satisfactory solution for large hiatal hernia repair concomitant with laparoscopic sleeve gastrectomy that may achieve a durable repair with low GERD symptoms.

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 wild-type 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.

Background: Staple line reinforcement material has been demonstrated to raise the burst pressure threshold after linear intestinal stapling. Numerous bioprosthetic materials have been utilized in surgical practice. Porcine urinary bladder matrix (ACell, Inc.) is an extracellular matrix material derived from porcine bladder used to reinforce surgically repaired soft tissue, and facilitate the body’s regenerative capacity. Objective: This study represents the first evaluation of urinary bladder matrix in gastrointestinal staple line reinforcement. Methods: Pathogen-free pigs underwent midline laparotomy under general anesthesia. Small intestinal division was performed with an endoscopic linear stapler. Nineteen intestinal divisions were performed with urinary bladder matrix staple line reinforcement, and twenty divisions were unreinforced. Staple lines were then subjected to burst pressure analysis by intraluminal infusion of dyed Krebs solution at an infusion rate of 20 ml·min-1 under manometric monitoring. Upon visible staple line extravasation, intraluminal pressure was recorded. Results: Intestinal staple lines reinforced with urinary bladder matrix exhibited significantly higher burst pressure threshold (p

Large-conductance Ca2+-activated potassium (BKCa) channels are key determinants of vascular smooth muscle excitability. Impaired BKCa channel function through remodeling of BKCa β1 expression and function contributes to vascular complications in animal models of diabetes. Yet, whether similar alterations occur in native vascular smooth muscle from humans with type 2 diabetes is unclear. In this study, we evaluated BKCa function in vascular smooth muscle from small resistance adipose arteries of non-diabetic and clinically diagnosed type 2 diabetic patients. We found that BKCa channel activity opposes pressure-induced constriction in human small resistance adipose arteries, and this is compromised in arteries from diabetic patients. Consistent with impairment of BKCa channel function, the amplitude and frequency of spontaneous BKCa currents, but not Ca2+ sparks were lower in cells from diabetic patients. BKCa channels in diabetic cells exhibited reduced Ca2+ sensitivity, single-channel open probability and tamoxifen sensitivity. These effects were associated with decreased functional coupling between BKCa α and β1 subunits, but no change in total protein abundance. Overall, results suggest impairment in BKCa channel function in vascular smooth muscle from diabetic patients through unique mechanisms, which may contribute to vascular complications in humans with type 2 diabetes.

Regulation of colonic motility depends on the integrity of enteric inhibitory neurotransmission mediated by nitric oxide (NO), purine neurotransmitters, and neuropeptides. Intramuscular interstitial cells of Cajal (ICC-IM) and platelet-derived growth factor receptor-α-positive (PDGFRα+) cells are involved in generating responses to NO and purine neurotransmitters, respectively. Previous studies have suggested a decreased nitrergic and increased purinergic neurotransmission in KitW/KitW-v ( W/Wv) mice that display lesions in ICC-IM along the gastrointestinal tract. However, contributions of NO to these phenotypes have not been evaluated. We used small-chamber superfusion assays and HPLC to measure the spontaneous and electrical field stimulation (EFS)-evoked release of nicotinamide adenine dinucleotide (NAD+)/ADP-ribose, uridine adenosine tetraphosphate (Up4A), adenosine 5′-triphosphate (ATP), and metabolites from the tunica muscularis of human, monkey, and murine colons and circular muscle of monkey colon, and we tested drugs that modulate NO levels or blocked NO receptors. NO inhibited EFS-evoked release of purines in the colon via presynaptic neuromodulation. Colons from W/Wv, Nos1−/−, and Prkg1−/− mice displayed augmented neural release of purines that was likely due to altered nitrergic neuromodulation. Colons from W/Wv mice demonstrated decreased nitrergic and increased purinergic relaxations in response to nerve stimulation. W/Wv mouse colons demonstrated reduced Nos1 expression and reduced NO release. Our results suggest that enhanced purinergic neurotransmission may compensate for the loss of nitrergic neurotransmission in muscles with partial loss of ICC. The interactions between nitrergic and purinergic neurotransmission in the colon provide novel insight into the role of neurotransmitters and effector cells in the neural regulation of gastrointestinal motility. NEW & NOTEWORTHY This is the first study investigating the role of nitric oxide (NO) and intramuscular interstitial cells of Cajal (ICC-IM) in modulating neural release of purines in colon. We found that NO inhibited release of purines in human, monkey, and murine colons and that colons from KitW/KitW-v ( W/Wv) mice, which present with partial loss of ICC-IM, demonstrated augmented neural release of purines. Interactions between nitrergic and purinergic neurotransmission may affect motility in disease conditions with ICC-IM deficiencies.

Enteric purinergic motor neurotransmission, acting through P2Y1 receptors (P2Y1R), mediates inhibitory neural control of the intestines. Recent studies have shown that NAD(+) and ADP ribose better meet criteria for enteric inhibitory neurotransmitters in colon than ATP or ADP. Here we report that human and murine colon muscles also release uridine adenosine tetraphosphate (Up4A) spontaneously and upon stimulation of enteric neurons. Release of Up4A was reduced by tetrodotoxin, suggesting that at least a portion of Up4A is of neural origin. Up4A caused relaxation (human and murine colons) and hyperpolarization (murine colon) that was blocked by the P2Y1R antagonist, MRS 2500, and by apamin, an inhibitor of Ca(2+)-activated small-conductance K(+) (SK) channels. Up4A responses were greatly reduced or absent in colons of P2ry1(-/-) mice. Up4A induced P2Y1R-SK-channel-mediated hyperpolarization in isolated PDGFRα(+) cells, which are postjunctional targets for purinergic neurotransmission. Up4A caused MRS 2500-sensitive Ca(2+) transients in human 1321N1 astrocytoma cells expressing human P2Y1R. Up4A was more potent than ATP, ADP, NAD(+), or ADP ribose in colonic muscles. In murine distal colon Up4A elicited transient P2Y1R-mediated relaxation followed by a suramin-sensitive contraction. HPLC analysis of Up4A degradation suggests that exogenous Up4A first forms UMP and ATP in the human colon and UDP and ADP in the murine colon. Adenosine then is generated by extracellular catabolism of ATP and ADP. However, the relaxation and hyperpolarization responses to Up4A are not mediated by its metabolites. This study shows that Up4A is a potent native agonist for P2Y1R and SK-channel activation in human and mouse colon.

Hypercontractility of arterial myocytes and enhanced vascular tone during diabetes are, in part, attributed to the effects of increased glucose (hyperglycemia) on L-type CaV1.2 channels. In murine arterial myocytes, kinase-dependent mechanisms mediate the increase in CaV1.2 activity in response to increased extracellular glucose. We identified a subpopulation of the CaV1.2 channel pore-forming subunit (α1C) within nanometer proximity of protein kinase A (PKA) at the sarcolemma of murine and human arterial myocytes. This arrangement depended upon scaffolding of PKA by an A-kinase anchoring protein 150 (AKAP150) in mice. Glucose-mediated increases in CaV1.2 channel activity were associated with PKA activity, leading to α1C phosphorylation at Ser1928. Compared to arteries from low-fat diet (LFD)–fed mice and nondiabetic patients, arteries from high-fat diet (HFD)–fed mice and from diabetic patients had increased Ser1928 phosphorylation and CaV1.2 activity. Arterial myocytes and arteries from mice lacking AKAP150 or expressing mutant AKAP150 unable to bind PKA did not exhibit increased Ser1928 phosphorylation and CaV1.2 current density in response to increased glucose or to HFD. Consistent with a functional role for Ser1928 phosphorylation, arterial myocytes and arteries from knockin mice expressing a CaV1.2 with Ser1928 mutated to alanine (S1928A) lacked glucose-mediated increases in CaV1.2 activity and vasoconstriction. Furthermore, the HFD-induced increases in CaV1.2 current density and myogenic tone were prevented in S1928A knockin mice. These findings reveal an essential role for α1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes.

Introduction. 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.

Platelet-derived growth factor receptor alpha (PDGFRα)+ cells are distributed into distinct morphological groups within the serosal, muscular, and submucosal layers as well as the myenteric and deep muscular plexi. PDGFRα+ cells directly interact with interstitial cells of Cajal (ICC) and smooth muscle cells (SMC) in gastrointestinal smooth muscle tissue. These three cell types, SMC, ICC, and PDGFRα+ cells (SIP cells), form an electrical syncytium, which dynamically regulates gastrointestinal motility. We have previously reported the transcriptomes of SMC and ICC. To complete the SIP cell transcriptome project, we obtained transcriptome data from jejunal and colonic PDGFRα+ cells. The PDGFRα+ cell transcriptome data were added to the Smooth Muscle Genome Browser that we previously built for the genome-scale gene expression data of ICC and SMC. This browser provides a comprehensive reference for all transcripts expressed in SIP cells. By analyzing the transcriptomes, we have identified a unique set of PDGFRα+ cell signature genes, growth factors, transcription factors, epigenetic enzymes/regulators, receptors, protein kinases/phosphatases, and ion channels/transporters. We demonstrated that the low voltage-dependent T-type Ca2+ channel Cacna1g gene was particularly expressed in PDGFRα+ cells in the intestinal serosal layer in mice. Expression of this gene was significantly induced in the hyperplasic PDGFRα+ cells of obstructed small intestine in mice. This gene was also over-expressed in colorectal cancer, Crohn's disease, and diverticulitis in human patients. Taken together, our data suggest that Cacna1g exclusively expressed in serosal PDGFRα+ cells is a new pathological marker for gastrointestinal diseases.

Background and objectives 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.

Laparoscopic ventral hernia repair with carboxymethylcellulose-sodium hyaluronate coating appears to be safe, effective, and durable., Background: Repair of ventral hernias, including primary ventral hernias and incisional ventral hernias, is performed in the United States 90,000 times per year. Open or traditional ventral hernia repairs involve the significant morbidity and expense of a laparotomy and a significant risk of recurrent herniation. Laparoscopic ventral hernia repair (LVHR) may offer a less-invasive alternative with shorter length of hospital stay, fewer cardiopulmonary complications, and low recurrence rates. Methods: 225 patients underwent laparoscopic ventral hernia repairs in which carboxymethylcellulose-sodium hyaluronate coating (Sepramesh, Davol, Providence, RI) was used primarily. All cases were included prospectively from the study period of 2002 through 2009. Patient characteristics were recorded, and follow-up analysis was performed over a period of 42 mo following surgery. Recurrence, reoperations, and all complications were recorded. Mesh awareness and mesh-related pain were assessed using the hernia-specific Carolinas Comfort Scale (CCS) instrument, completed by 72 patients. Results: Over 42 mo of follow-up, 2 ventral hernias have recurred, and no long-term bowel erosion or fistulization has occurred. Little or no mesh-related symptoms were reported, and mean scores for mesh awareness and mesh pain were 3.6 and 3.2, respectively, on a scale from 0–40 (lower scores signify less pain or awareness). Two serious early complications occurred related to intestinal ileus and metal tacks producing intestinal perforation, and this led to a change in the tacking devices used. Conclusions: LVHR with carboxymethylcellulose-sodium hyaluronate coating (Sepramesh) is safe and effective. Complications are rare, the repair is durable, and long-term results are good with rare recurrences, low awareness of mesh, and little pain. Technical lessons include use of at least one transfascial suture and the avoidance of metal tacks for fixation.

Introduction: Microperforation of the stomach following bariatric surgical procedures is often treated with endoluminal stent placement. Endoluminal stents migrate out of the desired position in a high frequency of cases. case series: this paper reports a series of five cases in which endoluminal stents migrated antegrade into unfavorable positions. One of the cases resulted in the stent migrating into the jejunum where it resulted in a jejunal perforation requiring surgery and bowel resection. After endoscopic repositioning of the stents, endoluminal suture fixation resulted in stabilization of the stents, prevented further migration, and facilitated clinical resolution of gastric fistula. No complications of the endoluminal suture fixation to the esophageal wall occurred, and all patients recovered fully. conclusion: this paper presents five cases of migrated gastroesophageal stents that were successfully secured with endoluminal sutures without complications. Endoluminal suturing may be a technically straightforward and useful solution to the migration of gastroesophageal stents.

Introduction: Parastomal hernias are a common complication of ileostomy and colostomy creation. Most are managed non-operatively, but some require surgery because of progressive symptoms and obstruction. Porcine urinary bladder matrix (UBM), utilized in many hernia applications, serves as an effective biologically-derived extracellular matrix scaffold and facilitates a favorable remodeling response with restoration of site-appropriate tissue. Case Series: Herein, eight cases are presented which describe four different techniques of parastomal hernia repair utilizing porcine UBM. In four cases, repair was performed through open laparotomy; the remaining four were performed laparoscopically. All repairs were reinforced with porcine UBM. Median duration of follow-up is 23 months. Conclusion: Surgeons may safely employ open and laparoscopic techniques for successful repair of parastomal hernias. In this series of eight cases, repairs with porcine UBM devices have proven durable at two years of follow-up and may serve as an alternative to synthetic mesh. (This page in not part of the published article.) International Journal of Case Reports and Images, Vol. 7 No. 2, February 2016. ISSN – [0976-3198] Int J Case Rep Images 2016;7(2):85–91. www.ijcasereportsandimages.com Sasse et al. 85 CASE REPORT OPEN ACCESS Parastomal hernia repair with urinary bladder matrix grafts: A case series Kent C. Sasse, David L. Warner, Ellen Ackerman, Jared Brandt

Patients undergoing Roux-en-Y gastric bypass for the resolution of morbid obesity have significant medical sequelae related to their weight. One of the most common comorbid conditions is joint pain requiring the use of non-steroidal anti-inflammatory medications (NSAIDs). In addition to NSAIDs, patients may engage in behaviors such as smoking and alcohol misuse that increase the risk of long-term postoperative complications to include gastric perforation. Data on 1,690 patients undergoing gastric bypass surgery were collected prospectively and reviewed retrospectively. We identified seven patients who presented to an emergency room and subsequently required emergent surgical intervention for repair of gastric perforation. Six of the seven cases involved use or abuse of NSAIDs. Important characteristics were identified including the use of NSAIDs, alcohol use, and non-compliance with routine long-term postoperative follow-up. Identifying those patients at high risk may decrease the incidence of this potentially life-threatening complication.

Introduction: Enterocutaneous fistula (EcF) represents a challenging clinical condition in surgery. two cases of EcF are presented that were successfully treated with Matristem, a porcine urinary bladder matrix xenograft application. case series: the cases were treated with a procedure involving curettage of the tract, followed by injection of a Matristem slurry, and insertion of a rolled Matristem graft. In both cases, the EcF ceased to drain bilious fluid. After a week, both patients began a liquid diet, and no recurrent fistula occurred after six months of follow-up. conclusion: In this study, treatment of EcF using Matristem resulted in successful clinical healing of the EcF. the use of biologically derived materials for EcF is a relatively new concept. there is precedent for using biological plugs with some reported examples of success, but use of porcine urinary bladder matrix is novel for this purpose.

Complex open pilonidal wounds represent a challenging wound healing problem. Nine cases of complex open pilonidal wounds are described. Each of them was treated at the time of primary wide excision with placement of xenograft extracellular matrix material derived from urinary bladder (MatriStem, ACell Corporation). The patients left the xenograft material and dressings intact and returned to our clinic at weekly intervals for inspection of the wounds. All of the cases of complex open pilonidal wounds healed without infection and without requiring re-operation. The average time to healing in this series was 7 weeks. Treatment of complex open pilonidal wounds with MatriStem extracellular matrix derived from urinary bladder in this fashion results in favorable wound healing of complex open pilonidal wounds.

To evaluate the long-term survival of critically ill patients with sepsis and to assess the factors predictive of long-term survival (1 month after admission date).Prospective, cohort study.Medical/surgical intensive care unit (ICU) in a multidisciplinary community hospital.All patients admitted to the ICU from January 1, 1987 to March 31, 1991 who both demonstrated clinical evidence of the systemic inflammatory response syndrome and yielded blood cultures positive for a bacterium or fungus (n = 153).Random set of procedures normally performed in an ICU setting.Patient characteristics, including age, blood culture results, comorbid conditions, and severity of illness as estimated by the Acute Physiology Score of the Acute Physiology and Chronic Health Evaluation II prognostic system were recorded. Follow-up evaluation utilizing the National Death Index provided survival outcome for all patients 1 yr after hospital discharge. The mortality rate at hospital discharge was 51.0%, and mortality rates at 1 month, 6 months, and 1 yr after admission date were 40.5%, 64.7%, and 71.9%, respectively. A total of 33 patients survived beyond the period of observation. The analyses demonstrated the following findings: a) the survival rate was negatively correlated with the Acute Physiology Score up to 1 month after hospital admission date, but uncorrelated thereafter; b) fungal infections, such as Candida, had the shortest survival prospects of any blood-borne infection; and c) both malignancy and human immunodeficiency virus infection contributed to poorer outcomes, but differed in their patterns of long-term survival.The most critical period for surveillance of bacteremic patients was in months 2 through 6 after discharge, during which time, the percentage of patients surviving decreased dramatically. The degree of physiologic derangement, as measured by the Acute Physiology Score, was a useful measure of prognosis within the first month after the score was assessed at ICU admission. However, beyond this period, prognostic utility decreased significantly. Healthcare providers should use caution concerning the expected survival of hospitalized patients with human immunodeficiency virus, based on experience with distinct conditions, such as malignancies.

Objectives: 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)