Peritoneal Space Research Articles

ROBOTIC TRANS-ABDOMINAL PREPERITONEAL APPROACH (TAPP) APPROACH FOR LATERAL INCISIONAL HERNIAS.

ABSTRACT Background: Lateral incisional hernias arise between the linea alba and the posterior paraspinal muscles. Anatomical boundaries contain various topographic variations, such as multiple nearby bony structures and paucity of aponeurotic tissue that make it particularly challenging to repair. Aim: To describe a robotic assisted surgical technique for incisional lumbar hernia repair. Methods: Retrospective data was collected from four patients who underwent robotic-assisted repair of their lumbar hernias after open nephrectomies. Results:Age ranged from 41-53 y. Two patients had right sided flank hernias while the other two on the left. One patient had a recurrent hernia on the left side. The patients were placed in lateral decubitus position contralateral to the hernia defect side. A trans-abdominal preperitoneal approach was used in all cases. Each case was accomplished with two 8 mm robotic ports, a 12 mm periumbilical port, and a 5 mm assistance port that allowed docking on the ipsilateral hernia side. The hernias were identified, a preperitoneal plane was created, and the hernia sac completely dissected allowing for complete visualization of the defect. All defects were primarily closed. Polypropylene or ProGripTM mesh was applied with at least 5 cm overlap and secured using either #0 Vicryl® transfacial sutures, Evicel® or a combination of both. The peritoneal space was closed with running suture and the ports were removed and closed. The average surgical length was 4 hr. The post-operative length of stay ranged from 0-2 days. Conclusion: The robotics platform may provide unique advantages in the repair of lateral incisional hernias and represents a safe, feasible and effective minimally invasive approach for the correction of lateral incisional hernias.

Established fibrous peritoneal metastasis in an immunocompetent mouse model similar to clinical immune microenvironment of gastric cancer

BackgroundPeritoneal metastasis (PM) in gastric cancer (GC) is characterized by diffusely infiltrating and proliferating cancer cells accompanied by extensive stromal fibrosis in the peritoneal space. The prognosis of GC with PM is still poor regardless of the various current treatments. In order to elucidate the cause of difficulties in PM treatment, we compared the tumor immune microenvironment (TME) in primary and PM lesions in GC. In addition, a PM model with fibrous stroma was constructed using immunocompetent mice to determine whether its TME was similar to that in patients.MethodsImmuno-histochemical analyses of infiltrating immune cells were performed in paired primary and PM lesions from 28 patients with GC. A C57BL/6 J mouse model with PM was established using the mouse GC cell line YTN16 either with or without co-inoculation of mouse myofibroblast cell line LmcMF with α-SMA expression. The resected PM from each mouse model was analyzed the immunocompetent cells using immunohistochemistry.ResultsThe number of CD8+ cells was significantly lower in PM lesions than in primary lesions (P < 0.01). Conversely, the number of CD163+ cells (M2 macrophages) was significantly higher in PM lesions than in primary lesions (P = 0.016). Azan staining revealed that YTN16 and LmcMF co-inoculated tumors were more fibrous than tumor with YTN16 alone (P < 0.05). Co-inoculated fibrous tumor also showed an invasive growth pattern and higher progression than tumor with YTN16 alone (P = 0.045). Additionally, YTN16 and LmcMF co-inoculated tumors showed lower infiltration of CD8+ cells and higher infiltration of M2 macrophages than tumors with YTN16 alone (P < 0.05, P < 0.05). These results indicate that LmcMF plays as cancer-associated fibroblasts (CAFs) by crosstalk with YTN16 and CAFs contribute tumor progression, invasion, fibrosis, and immune suppression.ConclusionsThis model is the first immunocompetent mouse model similar to TME of human clinical PM with fibrosis. By using this model, new treatment strategies for PM, such as anti-CAFs therapies, may be developed.

Interventional Radiology Placement and Management of Tunneled Peritoneal Dialysis Catheters: A Pictorial Review.

Interventional radiology (IR) is an underutilized resource for the placement and management of tunneled peritoneal dialysis (PD) catheters, as only about 5% of PD catheters are placed by using IR. PD is a cost-effective and physiologically beneficial alternative to hemodialysis (HD) with an increased survival benefit and lower complication rate than HD. As a home dialysis therapy, patients who undergo PD experience many advantages over patients who undergo HD, including a greater sense of well-being and quality of life. The author explains the history, need, rationale, benefits, complications, patient selection, preprocedure patient evaluation and preparation, catheter selection, procedural directives, and management strategies of IR involvement in tunneled PD catheter placement. Surgical and non-image-guided placement techniques and pitfalls are also discussed, and their benefits and limitations are compared with the cost-effective percutaneous image-guided IR technique. Specific attention to image-documented placement of the PD catheter coil into the retrovesical or retrouterine space is emphasized for optimal PD catheter function, as the retrovesical or retrouterine space is the most dependent portion of the peritoneal space and is void of omentum and small bowel. These features increase the functional ability of the PD catheter to effectively exchange the dialysate fluid and avoid complications such as omental wrap. IR, as an image-based specialty, is well positioned to evaluate for other complications of tunneled PD catheters such as migration, catheter kink and obstruction, and catheter leak. The demand for PD is predicted to increase in the future, and IR is strategically situated to become a leader in tunneled PD catheter placement and management. Published under a CC BY 4.0 license.

HIPEC plus EPIC paclitaxel for maximal perioperative treatments of advanced epithelial ovarian cancer. Long-term results of a pilot study

BackgroundA unique time in which to effectively treat an intraabdominal malignancy is the time at which the surgeon attempts complete removal of the malignant process. Although surgery is effective for visible disease, micrometastases or multiple small cancer nodules are not amenable to resection. Alternative interventions to deal with residual disease disseminated on peritoneal surfaces are needed. Materials and methodsCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) can be combined with early postoperative intraperitoneal chemotherapy (EPIC) in order to maximally treat gross disease within the abdomen and pelvis and also the minimal residual disease that exists in many patients after resection. The third component of this treatment for ovarian malignancy was EPIC paclitaxel in this study. The clinical features, pharmacologic assessments, and survival were determined in ovarian cancer patients in whom EPIC was added to the perioperative treatment plan. ResultsPatients with high grade serous ovarian cancer underwent CRS, HIPEC with cisplatin/doxorubicin, and EPIC paclitaxel. These treatments combined as a single intervention were studied in 10 patients. The median number of peritonectomy procedures was 1, the median number of visceral resections was 5, and the median time required in the operating room was 8 h. Two patients had a class 3 adverse event. The median survival of patients was 50 months. Pharmacokinetic analysis of the intraperitoneal paclitaxel showed 252 ± 153 times exposure of peritoneal surfaces as compared to intravenous exposure when the drug was instilled into the peritoneal space. ConclusionsEPIC paclitaxel was successfully combined with CRS and HIPEC in 10 patients with ovarian cancer. The treatment was tolerated approximately the same as other major cytoreductive surgical procedures for ovarian cancer or other malignancies. Survival of these ovarian cancer patients seemed unusually prolonged as compared to other patients with stage 3b or recurrent disease. In this pilot study CRS, HIPEC and EPIC were safe and effective.

A non-opioid analgesic implant for sustained post-operative intraperitoneal delivery of lidocaine, characterized using an ovine model

Appropriate management of post-operative pain is an ongoing challenge in surgical practice. At present, systemic opioid administration is routinely used for analgesia in the post-operative setting. However, due to significant adverse effects and potential for misuse, there is a perceived need for the development of alternative, opioid-sparing treatment modalities. Continuous infusion of local anesthetic into the peritoneum after major abdominal surgery reduces pain and opioid consumption, and enhances recovery from surgery. Here we describe a non-opioid, poly(ethylene-co-vinyl-acetate) intraperitoneal implant for the sustained delivery of local anesthetic following major abdominal surgery. A radio-opaque core had the required mechanical strength to facilitate placement and removal procedures. This core was enclosed by an outer shell containing an evenly dispersed local anesthetic, lidocaine. Sustained release of lidocaine was observed in an ovine model over days and the movement modelled between peritoneal fluid and circulating plasma. While desirably high levels of lidocaine were achieved in the peritoneal space these were several orders of magnitude higher than blood levels, which remained well below toxic levels. A pharmacokinetic model is presented that incorporates in vitro release data to describe lidocaine concentrations in both peritoneal and plasma compartments, predicting similar release to that suggested by lidocaine concentrations remaining in the device after 3 and 7 days in situ. Histological analysis revealed similar inflammatory responses following implantation of the co-extruded implant and a commercially used silicone drain after three days. This non-opioid analgesic implant provides sustained release of lidocaine in an ovine model and is suitable for moving onto first in human trials.

Evaluation of small bowel motion and feasibility of using the peritoneal space to replace bowel loops for dose constraints during intensity-modulated radiotherapy for rectal cancer

BackgroundThe goal of this study was to assess small bowel motion and explore the feasibility of using peritoneal space (PS) to replace bowel loops (BL) via the dose constraint method to spare the small bowel during intensity-modulated radiotherapy (IMRT) for rectal cancer.MethodsA total of 24 patients with rectal cancer who underwent adjuvant or neoadjuvant radiotherapy were selected. Weekly repeat CT scans from pre-treatment to the fourth week of treatment were acquired and defined as Plan, 1 W, 2 W, 3 W, and 4 W. The 4 weekly CT scans were co-registered to the Plan CT, BL and PS contours were delineated in all of the scans, an IMRT plan was designed on Plan CT using PS constraint method, and then copied to the 4 weekly CT scans. The dose-volume, normal tissue complication probability (NTCP) of the small bowel and their variations during treatment were evaluated.ResultsOverall, 109 sets of CT scans from 24 patients were acquired, and 109 plans were designed and copied. The BL and PS volumes were 250.3 cc and 1339.3 cc. The V15 of BL and PS based plan of pre-treatment were 182.6 cc and 919.0 cc, the shift% of them were 28.9 and 11.3% during treatment (p = 0.000), which was less in the prone position than in the supine position (25.2% vs 32.1%, p = 0.000; 9.9% vs 14.9%, p = 0.000). The NTCPC and NTCPA based plan of pre-treatment were 2.0 and 59.2%, the shift% during treatment were 46.1 and 14.0% respectively. Majority of BL’s Dmax and V15 were meet the safety standard during treatment using PS dose limit method except 3 times (3/109) of V15 and 5 times of Dmax (5/109).ConclusionsThis study indicated that small bowel motion may lead to uncertainties in its dose volume and NTCP evaluation during IMRT for rectal cancer. The BL movements were significantly greater than PS, and the prone position was significantly less than the supine position. It is feasibility of using PS to replace BL to spare the small bowel, V15 < 830 cc is the dose constraint standard.

Preclinical evaluation of liposome-supported peritoneal dialysis for the treatment of hyperammonemic crises

Liposome-supported peritoneal dialysis (LSPD) with transmembrane pH-gradient liposomes was previously shown to enhance ammonia removal in cirrhotic rats and holds promise for the treatment of hyperammonemic crises-associated disorders. The main objective of this work was to conduct the preclinical evaluation of LSPD in terms of pharmacokinetics, ammonia uptake, and toxicology to seek regulatory approval for a first-in-human study. The formulation containing citric acid-loaded liposomes was administered intraperitoneally at two different doses once daily for ten days to healthy minipigs. It was also tested in a domestic pig model of hyperammonemia. The pharmacokinetics of citric acid and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine was linear following intraperitoneal administration of medium and high dose. There was no systemic accumulation following daily doses over ten days. The systemic exposure to phospholipids remained low. Furthermore, the liposome-containing peritoneal fluid contained significantly higher ammonia levels than the liposome-free control, demonstrating efficient ammonia sequestration in the peritoneal space. This was indeed confirmed by the ability of LSPD to decrease plasmatic ammonia levels in artificially induced hyperammonemic pigs. LSPD was well tolerated, and no complement activation-related pseudoallergy reactions were observed. The safety profile, the linear pharmacokinetics of citric acid following repeated administrations of LSPD as well as the linear dose-dependent ammonia sequestration in the peritoneal space provide a strong basis for the clinical investigation of LSPD.

Abstract B68: Characterization of microtentacle phenotype and function in ovarian carcinomas

Abstract Ovarian carcinomas are categorized into five major histotypes, each characterized by distinct differences in grade at diagnosis, presentation with metastatic disease, and clinical responses to treatments. Microtentacles (McTNs), microtubule-based extensions of the plasma membrane, were initially described on cells of nongynecologic primaries with high metastatic potential but have not been extensively explored in ovarian carcinomas. In this study, we investigated whether ovarian cancer cells exhibit McTNs as well as the effect of microtubule-targeted drugs on ovarian cancer McTNs. We analyzed 3 immortalized ovarian surface epithelium cell lines (IOSE), 8 clear-cell (OCCC), 3 low-grade serous (LGS), and 6 high-grade serous (HGS) ovarian cancer cells for McTN phenotype, length, and number, using a novel tethering platform in which cells are suspended but stationary, allowing for analysis via confocal microscopy. Additionally, selected cell lines were also treated with microtubule-targeting agents, including paclitaxel, ixabepilone, vinblastine, and colchicine and the effects on McTN dynamics and functions were analyzed. Tubulin subtype expression and post-translational modifications (PTM) were characterized by Western blot. Unpaired t-tests were used to describe differences between McTN length and number. We observed 4 patterns of McTN expression: absent (A), symmetric-short (SS), symmetric-long (SL), and tufted (T). In some cases, multiple morphologies were observed within the same cell line. LGS and OCCC expressed fewer McTNs per cell than HSC. McTNs were shorter among OCCC compared to HGS; whereas LGS expressed a range of McTN lengths similar to those observed in HGS. We also observed differences in the expression of the PTM between the different ovarian cancer subtypes, including alterations in alpha tubulin-stabilizing modifications such as glu-tubulin and acetylated tubulin, as well as proteins involved in actin cortex stability. Increased acetylated tubulin was associated with increased McTN number and length in HGS cells. Microtubule-destabilizing drugs such as colchicine and vinblastine led to a decrease in McTN formation. Ovarian cancer metastasis typically occurs through shedding of the main tumor into the peritoneal space, and the spread of disease is the leading cause of mortality. Studying McTN function and response to chemotherapeutics allows us to improve our understanding of ovarian cancer metastasis and the effect of microtubule-targeting compounds on the spread of ovarian cancer. Citation Format: Cong (Ava) Fan, Sulan Wu, Jocelyn Reader, Eleanor Claire-Higgins Ory, Cornell Lee, McMillan Ching, Trevor Mathias, Julia Ju, Rachel Lee, Michele Vitolo, Stuart Martin, Christopher Jewell, Amy Fulton, Gautam Rao, Mark Carey, Dana M. Roque. Characterization of microtentacle phenotype and function in ovarian carcinomas [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr B68.

Giant splenic artery aneurysm presenting with massive upper gastrointestinal bleeding: A case report and review of literature

BACKGROUNDSplenic artery aneurysm (SAA) and pseudoaneurysm are rare vessel’s lesions. Pseudoaneurysm is often symptomatic and secondary to pancreatitis or trauma. True SAA is the most common aneurysm of visceral vessels. In contrast to pseudoaneurysm, SAA is usually asymptomatic until the rupture, with high mortality rate. The clinical onset of SSA’s rupture is a massive life-threatening bleeding with hemodynamic instability, usually into the free peritoneal space and more rarely into the gastrointestinal tract.CASE SUMMARYWe describe the case of a 35-year-old male patient, with negative past medical history, who presented to the emergency department for massive upper gastrointestinal bleeding, severe anemia and hypotension. An esophagogastroduodenoscopy performed in emergency showed a gastric bulging in the greater curvature/posterior wall with a small erosion on its surface, with a visible vessel, but no active bleeding. Endoscopic injection therapy with cyanoacrylate glue was performed. Urgent contrast-enhanced computed tomography was carried out due to the clinical scenario and the unclear endoscopic aspect: The radiological examination showed a giant SAA which was adherent to posterior stomach wall, and some smaller aneurysms of the left gastric and ileocolic artery. Because of the high risk of a two-stage rupture of the giant SAA with dramatic outcome, the patient underwent immediate open surgery with aneurysmectomy, splenectomy and distal pancreatectomy with a good postoperative outcome.CONCLUSIONThe management of a ruptured giant SAA into the stomach can be successful with surgical approach.

Tuning the Physicochemical Characteristics of Particle-Based Carriers for Intraperitoneal Local Chemotherapy.

Over the last few decades, intraperitoneal (IP) local drug delivery, providing high drug concentrations with prolonged retention in the peritoneal cavity, has opened a new horizon for the management of life-threatening peritoneal disorders, such as peritoneal carcinomatosis (PC). However, clinical translation of this strategy is hampered by several hurdles, namely premature clearance of small-sized molecules from the peritoneum, limited distribution within the peritoneal space and inadequate penetration into the target tissues. To address these challenges, incorporation of therapeutic agents into the particulate-based drug delivery systems has brought new hope in this direction. Nonetheless, as yet, there has been no formulation specifically approved for IP delivery. To gain this goal, it is crucial to have a detailed understanding of the correlation between the physicochemical characteristics of particle-based carriers and their biological fate and anticancer efficacy after IP administration. The main focus of this review, therefore, concerns the significance of these characteristics, namely composition, particle size, charge, coating and presence of targeting moieties in the design of carriers for successful IP delivery. Graphical Abstract Physicochemical characteristics of particle-based carriers influence their peritoneal residence time, biological fate and anticancer efficacy after intraperitoneal administration.

Active Delivery of VLPs Promotes Anti-Tumor Activity in a Mouse Ovarian Tumor Model.

Virus-like nanoparticles (VLPs) have been used as an attractive means in cancer immunotherapy because of their unique intrinsic immunostimulatory properties. However, for treating metastatic tumors in the peritoneal cavity, such as ovarian cancer, multiple injections of therapy are needed due to the large peritoneal space and fast excretion of therapy. Here, it is reported on the development of active VLP delivery vehicles for the treatment of peritoneal ovarian tumors using biocompatible Qβ VLPs-loaded Mg-based micromotors. The autonomous propulsion of such Qβ VLPs-loaded Mg-micromotors in the peritoneal fluid enables active delivery of intact immunostimulatory Qβ VLPs to the peritoneal space of ovarian tumor bearing mice, greatly enhancing the local distribution and retention of Qβ VLPs. Such improved distribution and longer retention time of Qβ in the peritoneal cavity leads to enhanced immunostimulation and therefore increased survival rate of tumor-bearing mice compared to a passive Qβ treatment. For clinical translation, the active delivery of VLPs holds great promise for tumor immunotherapy toward the treatment of different types of primary and metastatic tumors in the peritoneal cavity.

Compartmental fat distribution in the abdomen of dogs relative to overall body fat composition

BackgroundAdipose tissue may have different metabolic and endocrine functions depending on the region of the body in which it is located. While visceral or intra-abdominal fat has been found to contribute to leptin concentrations, insulin resistance and obesity-related diseases, there are only a few imaging studies documenting the preferential distribution of body fat to either the intra-abdominal or subcutaneous compartments in dogs. This study aimed to determine if CT-measured abdominal fat distributed preferentially to the visceral space (V) relative to the subcutaneous space (SQ), with increasing DXA-determined total body fat percentage; and if ultrasound measurements of the ventral midline subcutaneous (SAT) and visceral adipose thickness (VAT) can be used to estimate the distribution of fat to the subcutaneous and visceral abdominal spaces, in a sample of 22 dogs with variable body condition.ResultsMultivariate analysis showed no statistically significant correlation between visceral to subcutaneous fat ratio (V/SQ) and increasing total body fat percentage (β = − 0.07, p = 0.733), but strong correlation with age (β = 0.71 p = 0.002). A substantial amount of variation for the ultrasound visceral adipose thickness to subcutaneous fat thickness (VAT/SAT) could be explained by both CT V/SQ and sex (R2Adjusted = 0.477, p = 0.001), with female dogs having significant lower VAT/SAT ratios compared to the male dogs (p = 0.047). The ultrasound fat measurements appeared moderately reliable, but a larger sample number is required to confirm this.ConclusionsThe findings suggest that dogs with a relatively healthy to slightly overweight body condition score, distribute fat relatively similarly between their peritoneal (visceral) and subcutaneous abdominal compartments with increasing total body fat percentage. However, there was increased fat distribution to the peritoneal space relative to the subcutaneous space with increasing age. Further, abdominal ultrasound may be useful in estimating the ratio of fat distribution to both the abdominal visceral and subcutaneous spaces.

THE CASE TREATMENT OF CYSTADENOMA OF THE PANCREAS

Summary. Introduction. Cystadenoma of the pancreas is a benign tumor in the form of a cyst of epithelial origin, which in the absence of adequate treatment disrupts the function of the pancreas, due to compression on nearby tissues, and in 3 % of cases regenerates into cystadenocarcinoma.&#x0D; Aim. Present a clinical case of surgical treatment of cystadenoma of the body of the pancreas, while preserving the caudal part of the latter to prevent the possible development of diabetes.&#x0D; Material and methods. Patient M., 72 years old, who was hospitalized in the infectious department of the central district hospital, during ultrasound of the abdominal cavity and peritoneal space revealed a neoplasm of the retroperitoneal space in the body and tail of the pancreas, in connection with which she was transferred to the surgery department. After the appropriate examination, the patient underwent surgery — laparotomy. Removal of a neoplasm of the body of the pancreas. Distal pancreatojejunoanastomosis, entero-enteroanastomosis. Abdominal drainage.&#x0D; Results. The postoperative period was without complications, drainage was removed, sutures were removed for 9-10 days, the wound healed with primary tension.&#x0D; In the section of the drug, there is a capsule with a wall thickness of up to 2.0 mm, which contains mucopurulent masses in the form of flakes. The outer wall of the capsule is covered with joints and vessels, and the inner has a shiny matte surface. The histopathological examination indicates cystadenoma of the pancreas.&#x0D; The choice to form a distal pancreatojejunostomy in contrast to the distal resection of the pancreas was due to the patient’s age and high probability of developing diabetes because it is in the caudal part of the pancreas is the lion’s number of islets of Langerhans.&#x0D; Conclusion. When performing radical surgical interventions on the pancreas in elderly and senile patients, it is necessary to preserve the tissues of the latter, especially the tail, to prevent the development of diabetes.

Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates.

We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes. Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 MRI was used to determine the locations of capsules within the peritoneal space on days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem. At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 ± 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 ± 7.5 mm Hg (day 0) and 89 ± 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether capsules retrieved on day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20 B cells, CD4 and CD8 T cells, and CD14 macrophages increased consistent with a mild foreign body reaction. The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.

Effects of dexamethasone, cyclosporine and betamethasone on inflammatory cell recruitment in mice infected with Strongyloides venezuelensis

The objective of this study was verified effect of immunosuppressant activities of Dexametasone (Dexa), Cyclosporine (CsA) and Betamethasone (Beta) in the synhteses of inflammatory cell and dissemination of Strongyloides venezuelensis. S. venezuelensis- infected mice increased total leucocytes (TL), eosinophil (EO), mononuclear cells (MC), and neutrophil (NE) numbers in the blood. The infection induced recruitment of TL, EO and MC to peritoneal cavity (PCF) and space bronchoalveolar (BALF), exception for NE. Dexa, CsA and Beta treatments inhibited TL, EO and MC production. However, Dexa treatment was associated with NE accumulation in the blood. Dexa and Beta tratments reductions migration of inflammatory cells from the blood to PCF and BALF. Infected mice and treated with Dexa and Beta worm parasites, eggs/g/feces and larvae recovered were higher than CsA. The results showed that glucocorticoid treatment may induce strongyloidiasis dissemination while CsA induced mice protection against S. venezuelensis infection.

Tissue-type plasminogen activator selectively inhibits multiple toll-like receptors in CSF-1-differentiated macrophages.

Tissue-type plasminogen activator (tPA) is a major activator of fibrinolysis, which also attenuates the pro-inflammatory activity of lipopolysaccharide (LPS) in bone marrow-derived macrophages (BMDMs) and in vivo in mice. The activity of tPA as an LPS response modifier is independent of its proteinase activity and instead, dependent on the N-methyl-D-aspartate Receptor (NMDA-R), which is expressed by BMDMs. The major Toll-like receptor (TLR) for LPS is TLR4. Herein, we show that enzymatically-inactive (EI) tPA blocks the response of mouse BMDMs to selective TLR2 and TLR9 agonists, rapidly reversing IκBα phosphorylation and inhibiting expression of TNFα, CCL2, interleukin-1β, and interleukin-6. The activity of EI-tPA was replicated by activated α2-macroglobulin, which like EI-tPA, signals through an NMDA-R-dependent pathway. EI-tPA failed to inhibit cytokine expression by BMDMs in response to agonists that target the Pattern Recognition Receptors (PRRs), NOD1 and NOD2, providing evidence for specificity in the function of EI-tPA. Macrophages isolated from the peritoneal space (PMs), without adding eliciting agents, expressed decreased levels of cell-surface NMDA-R compared with BMDMs. These cells were unresponsive to EI-tPA in the presence of LPS. However, when PMs were treated with CSF-1, the abundance of cell-surface NMDA-R increased and the ability of EI-tPA to neutralize the response to LPS was established. We conclude that the anti-inflammatory activity of EI-tPA is selective for TLRs but not all PRRs. The ability of macrophages to respond to EI-tPA depends on the availability of cell surface NMDA-R, which may be macrophage differentiation-state dependent.

Antimicrobial susceptibilities of the ertapenem-non-susceptible non-carbapenemase-producing Enterobacterales isolates causing intra-abdominal infections in the Asia-Pacific region during 2008–2014: Results from the Study for Monitoring the Antimicrobial Resistance Trends (SMART)

ObjectivesTo investigate the susceptibility profiles amongst ertapenem-non-susceptible non-carbapenemase-producing Enterobacterales (ETP-NS-non-CPE) isolates. MethodsMinimum inhibitory concentrations (MICs) of 404 ETP-NS-non-CPE isolates collected from different intra-abdominal infection (IAI) sites amongst patients in the Asia-Pacific region during 2008–2014 were determined using the broth microdilution method. The susceptibility results were interpreted according to the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute (CLSI) in 2018. The MICs data of several agents were evaluated based on their published pharmacokinetic/pharmacodynamic (PK/PD) profiles. ResultsThe majority (>84%) of IAI-ETP-NS-non-CPE isolates – including Escherichia coli (n=83), Klebsiella pneumoniae (n=91) and Enterobacter species (n=210) – were susceptible to imipenem and amikacin. The 193 hepatobiliary ETP-NS-non-CPE isolates exhibited a trend of lower cefepime MIC (≤4mg/L) distribution than those (n=145) cultured from the peritoneal space (P=0.058). Amongst the ETP-NS-non-CP Enterobacter isolates, 65.7% displayed a cefepime MIC≤4mg/L. In addition, compared with Escherichia coli and Klebsiella pneumoniae isolates, 82.9% and 72.9% of the ETP-NS-non-CP Enterobacter isolates were susceptible to levofloxacin and ciprofloxacin, respectively. Of note, 74.5% and 70.3% of the ETP-NS-non-CP Enterobacter isolates cultured from the hepatobiliary tract and peritoneal space exhibited a ciprofloxacin MIC≤2mg/L and ≤0.25mg/L, respectively. Imipenem and amikacin showed good in vitro susceptibility rates against the IAI-ETP-NS-non-CPE isolates. The hepatobiliary ETP-NS-non-CPE displayed lower cefepime MICs than those cultured from the peritoneal space. Additionally, a significant fraction of IAI-ETP-NS-non-CP Enterobacter isolates exhibited ciprofloxacin MIC ≤ 2mg/L. ConclusionBased upon the PK/PD analyses, ciprofloxacin, imipenem and cefepime are probably effective against IAI-ETP-NS-non-CPE isolates.

A novel laparoscopic approach: (e-TEP) technique in ventral abdominal hernia-our experience

Background: Enhanced view totally extra peritoneal (eTEP) repair is the novel method for inguinal hernia management. Igor Belyansky extended the principle of eTEP to ventral and incisional hernia. The eTEP technique is based on the principle that the extra peritoneal space can be created from almost anywhere in the anterior abdominal wall. The classical Totally Extra peritoneal (TEP) technique is considered closest to an ideal hernia repair, but this technique has several drawbacks such as restricted port placement, limited space for dissection and mesh placement, a low tolerance of accidental pneumoperitoneum, and difficulty in teaching and learning the technique. We present our experience with eTEP technique, which overcomes several of these drawbacks.Methods: We conducted a short term 6 months retrospective analysis of 24 patients in our hospital who underwent eTEP procedure for umbilical hernia and inguinal hernia, with a minimum of 3 months follow-up. Their data were analyzed for operative details, intra‑operative and post‑operative complications.Results: Judging from our short term results, for 24 patients we have not come across any post-operative complications like seroma, SSI, recurrence, with a minimum of 3 months follow-up.Conclusion: Our evaluation of eTEP technique in umbilical and inguinal hernias has found the approach not only novel one but also very feasible and highly effective. This technique provides flexible port set-up optimal for laparoscopic closure of defects, along with placement of wide mesh in the retro-muscular space with no transfascial fixation while restoring abdominal wall dynamics. We suggest that the eTEP technique is the most ideal option for ventral abdominal hernia repair and can be adapted in hospitals with advanced laparoscopic setup.

Zwitterionic amino acid-based Poly(ester urea)s suppress adhesion formation in a rat intra-abdominal cecal abrasion model

Hernia repair outcomes have improved with more robust material options for surgeons and optimized surgical techniques. However, ventral hernia repairs remain challenging with an inherent risk of post-surgical adhesions in the peritoneal space which can occur regardless of interventional material or its surgical placement. Herein, amino acid-based poly(ester urea)s (PEUs) with varied amount of an allyl ether side chains were modified post polymerization modification with the zwitterionic sulfnate group (3-((3-((3-mercaptopropanoyl)oxy)propyl) dimethylammonio)propane-1-sulfonate) to promote anti-adhesive properties. These alloc-PEUs were processed using roll-to-roll fabrication methods to afford films that were amenable to surface functionalization via a zwitterion-thiol. Functional group availability on the surface was confirmed via fluorescence microscopy, x-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance (QCM) measurements. Zwitterionic treated PEUs exhibited reduced fibrinogen adsorption in vitro when compared to unfunctionalized control polymer. A rat intrabdominal cecal abrasion adhesion model was used to assess the extent and tenacity of adhesion formation in the presence of the PEUs. The 10% alloc-PEU zwitterion functionalized material was found to reduce the extent and tenacity of adhesions when compared to adhesion controls and the unfunctionalized PEU controls.

Assessment of the aerosol distribution pattern of a single-port device for intraperitoneal administration of therapeutic substances.

In the last 20years, intraperitoneal chemotherapy (IPC) has been explored as a modality for the management of peritoneal metastases of gynecologic, gastrointestinal, and primary peritoneal tumors. Direct delivery of chemotherapeutic agents to the peritoneal cavity space has proved superior to systemic chemotherapy when evaluating characteristics such as drug concentration reached in the peritoneal space, penetration into peritoneal metastases, and chemotherapy-related toxicity. Traditionally, IPC is delivered by peritoneal lavage with a liquid solution. This form of delivery has limitations, including inhomogeneous intraperitoneal distribution and limited ability to penetrate tissues and metastatic nodules. An alternative mode of delivery is so-called pressurized intraperitoneal aerosol chemotherapy (PIPAC). Within this context, the present study sought to identify the pattern of spatial distribution of therapeutic solutions aerosolized into the peritoneal space using a single-port PIPAC device and ascertain whether the aerosolized method is superior to the traditional (liquid) mode of IPC delivery. Analysis of the rate of intra-abdominal staining with aerosolized 2% silver nitrate in five porcine models. Assessment of differences in stain impregnation between the upper, middle, and lower abdomen did not reveal significant differences (p = 0.42). The median sum scores were 1 for the upper abdomen and 3 for the middle and lower abdomen. Aerosolization does not reach all regions of the abdomen homogeneously. However, adequate exposure of the upper abdomen, mid-abdomen, and lower abdomen to chemotherapeutic agents can be achieved with PIPAC.