Dibenzo-Fused Heterocycles: A Decade Update on the Syntheses of Carbazole, Dibenzofuran, and Dibenzothiophene.

Polycyclic heterocycles are the most common and critical structural motifs found in a variety of natural products, medicines, fertilizers, and advanced materials. Because of their widespread use in biologically active compounds and material chemistry, functionalised dibenzo heterocyclic compounds, especially dibenzofuran, dibenzothiophene, and carbazole derivatives, garnered much attention over time. Scientists are especially interested in elucidating more efficient techniques for developing these industrially essential compounds. Dibenzo-fused heterocycles can rapidly be synthesised using highly efficient transition metal-catalysed strategies as well as by economic metal-free reaction conditions. This review includes a detailed overview of the most recent significant synthetic techniques, both metal-catalysed and metal-free, to produce these industrially significant and medicinally important dibenzo-fused heterocycles.

Ultrasound-guided dry needling of masticatory muscles in trigeminal neuralgia - A case series of 35 patients.

Background: Trigeminal neuralgia (TGN) is considered a sensory neuropathy. However, reports of pain on chewing/speaking suggest a masticatory myofascial involvement. Objective: To examine the effect of ultrasound-guided dry needling (USGDN), which deactivates myofascial trigger points in masticatory, neck, and facial muscles on TGN symptoms. Methods: Charts of 35 patients treated for TGN were retrospectively reviewed. Treatment was USGDN alone or combined with trigeminal ganglion/mandibular nerve pulsed radiofrequency (PRF), followed by yoga mudras to stretch masticatory and facial muscles. Patients were followed for 1-8 years. Outcome parameters were reduction of medications with reduction in neuralgic attack frequency and Numeric Rating Scale (NRS) score. Results: 23 patients (65.7%) received USGDN alone, 12 patients (34.3%) received PRF treatment before USGDN. A significant reduction in the mean (SD) NRS (5.7 [1.2] vs 8.8 [1.6]; P < .001) and neuralgic attack frequency (47 [27] vs 118 [70] attacks/day; P < .001) was seen after PRF compared with baseline, respectively. Following USGDN, the mean (SD) NRS further decreased significantly to 1.0 (0.9) (P < .001). USGDN alone produced a similar improvement in the NRS (8.9 [1.5] at baseline reduced to 0.6 [0.7] post-USGDN; P < .001). Patients in both groups reported a cessation in neuralgic attacks after USGDN. Post-USGDN, 18/27 patients completely discontinued medication, with the mean (SD) carbamazepine dose significantly reducing from 716.7 (260.9) mg/day at baseline to 113.0 (250.2) mg/day post-USGDN (P < .001). Conclusion: Decisive relief of TGN by USGDN suggests neuromyalgia involving masticatory muscles. Prospective, controlled studies could confirm these findings.

High light intensity aggravates latent manganese deficiency in maize.

Manganese (Mn) plays an important role in the oxygen-evolving complex, where energy from light absorption is used for water splitting. Although changes in light intensity and Mn status can interfere with the functionality of the photosynthetic apparatus, the interaction between these two factors and the underlying mechanisms remain largely unknown. Here, maize seedlings were grown hydroponically and exposed to two different light intensities under Mn-sufficient or -deficient conditions. No visual Mn deficiency symptoms appeared even though the foliar Mn concentration in the Mn-deficient treatments was reduced to 2 µg g-1. However, the maximum quantum yield efficiency of PSII and the net photosynthetic rate declined significantly, indicating latent Mn deficiency. The reduction in photosynthetic performance by Mn depletion was further aggravated when plants were exposed to high light intensity. Integrated transcriptomic and proteomic analyses showed that a considerable number of genes encoding proteins in the photosynthetic apparatus were only suppressed by a combination of Mn deficiency and high light, thus indicating interactions between changes in Mn nutritional status and light intensity. We conclude that high light intensity aggravates latent Mn deficiency in maize by interfering with the abundance of PSII proteins.

The iron-regulated transporter 1 plays an essential role in uptake, translocation and grain-loading of manganese, but not iron, in barley.

Transporters involved in manganese (Mn) uptake and intracellular Mn homeostasis in Arabidopsis and rice are well characterized, while much less is known for barley, which is particularly prone to Mn deficiency. In this study we have investigated the role of the iron-regulated transporter 1 (IRT1) for Mn uptake and translocation in barley plants. We employed an RNAi approach to reduce HvIRT1 expression to 5% of the wild-type level. This enabled characterization of the functional role of HvIRT1 by use of advanced imaging and phenotyping techniques applied to plants growing in hydroponics or soils with different Mn availability. Our results highlight the importance of HvIRT1 for the transport of Mn across the root endodermis into the stele. In the hvirt1-RNAi lines, a chlorotic phenotype with reduced shoot Mn concentration and impaired photosynthetic functionality was observed, especially under conditions with low Mn availability. We also document that HvIRT1 controlled the Mn distribution within the barley grain. Surprisingly, unlike other IRT1 orthologues, HvIRT1 played no significant role in iron uptake. We conclude that the barley IRT1 orthologue has a novel function with respect to ensuring sufficient shoot Mn concentrations. The preference of IRT1 for Mn instead of Fe is discussed in an evolutionary context.

Molecular speciation and tissue compartmentation of zinc in durum wheat grains with contrasting nutritional status.

Low concentration of zinc (Zn) in the endosperm of cereals is a major factor contributing to Zn deficiency in human populations. We have investigated how combined Zn and nitrogen (N) fertilization affects the speciation and localization of Zn in durum wheat (Triticum durum). Zn-binding proteins were analysed with liquid chromatography ICP-MS and Orbitrap MS(2) , respectively. Laser ablation ICP-MS with simultaneous Zn, sulphur (S) and phosphorus (P) detection was used for bioimaging of Zn and its potential ligands. Increasing the Zn and N supply had a major impact on the Zn concentration in the endosperm, reaching concentrations higher than current breeding targets. The S concentration also increased, but S was only partly co-localized with Zn. The mutual Zn and S enrichment was reflected in substantially more Zn bound to small cysteine-rich proteins (apparent size 10-30 kDa), whereas the response of larger proteins (apparent size > 50 kDa) was only modest. Most of the Zn-responsive proteins were associated with redox- and stress-related processes. This study offers a methodological platform to deepen the understanding of processes behind endosperm Zn enrichment. Novel information is provided on how the localization and speciation of Zn is modified during Zn biofortification of grains.

Mutations seen among patients with pheochromocytoma and paraganglioma at a referral center from India.

Determining the mutational status of susceptibility genes including RET, VHL, SDHx (SDHB, SDHC, SDHD) among patients with pheochromocytoma/paraganglioma (PCC/PGL) is gaining importance. These genes have not been systematically characterized among patients with PCC/PGL from India. The aim of the work was to screen the most frequently mutated genes among patients with PCC/PGL to determine the frequency and spectrum of mutations seen in this region. Fifty patients with PCC/PGL treated at our tertiary care hospital between January 2010 and June 2012 were screened for mutations in susceptibility genes using an algorithmic approach. Thirty-two percent (16/50) of patients were found to be positive for mutations including mutations among RET (n=4), VHL (n=6), SDHB (n=3), and SDHD (n=3) genes. None of these patients were positive for SDHC mutations. A significant association was found between young patients with bilateral tumors and VHL mutations (p=0.002). Two of the 3 patients with extra-adrenal SDHB associated tumors, had unique mutations, viz., c.436delT (exon 5) and c.788_857del (exon 8), one of which was malignant. High frequency of mutations seen among patients in this study emphasizes the need to consider mutational analysis among Indian patients with PCC/PGL.

Assessment of a novel, full-thickness incisional biopsy model to restage rectal tumours after neoadjuvant chemoradiotherapy: results of an ex vivo pilot study.

BACKGROUND: There is currently no reliable means to restage rectal cancers after neoadjuvant chemoradiation. Recent histological evidence shows that the epicentre for residual cancer cells is focussed directly underneath any residual mucosal abnormality (RMA). This proof-of-concept study aimed to determine the utility of a novel, minimally invasive method of incisional biopsy as a restaging tool. A secondary aim was to compare its performance to clinical response assessment. METHODS: After surgical resection, 0.5 × 0.5 cm, full-thickness incisional biopsy was performed in 15 rectal cancers. Of these, 13 had RMA and 2 had mucosal cCR but a palpable intramural abnormality. In all patients, a full-thickness incisional biopsy was taken through the centre of these areas. The ypT stage of the incisional biopsy and the final total specimen were compared. Complete mucosal clinical response was deemed to have occurred when either no residual tumour or only a flat mucosal scar remained. RESULTS: Incisional biopsy correctly identified all patients that had been downstaged to ypT0; however, it also falsely identified 5 of 10 patients (50%) with yp residual disease as ypT0. Overall performance of incisional biopsy to detect residual cancer was 50% sensitivity, 100 % specificity, 100% PPV, and 50% NPV with an accuracy of 66%. A complete mucosal clinical response occurred in only one of five patients downstaged to ypT0 (20% sensitive). It also occurred in one patient, which was ultimately staged as ypT3. CONCLUSION: This prospective data demonstrates that incisional biopsy is not suitable as a stand-alone method to restage rectal cancer after CRT. Alternate or complementary means of restaging are needed.

Depth and lateral spread of microscopic residual rectal cancer after neoadjuvant chemoradiation: implications for treatment decisions.

AIM: The aim of this study was to determine the distribution of residual tumour within the bowel wall in relation to residual mucosal abnormalities (RMAs) and surrounding normal mucosa in patients with rectal cancer who underwent neoadjuvant chemoradiation followed by curative surgery. METHOD: Archived pathological slides from a cohort of 60 patients with residual tumour were retrieved. The incidence, distance and depth of tumour spread (ypT) under RMAs and adjacent normal mucosa were reviewed and recorded. RESULTS: Histological sections containing both RMA and adjacent normal mucosa were available for 45 of 60 patients with ypT1 (n = 6), ypT2 (n = 18) and ypT3 (n = 21) disease. The maximal depth of invasion, as measured by ypT stage, was found underneath the RMA in 44 of 45 (98%) patients. Microscopic tumour spread lateral to the RMA and under adjacent normal mucosa was found in 32 of 45 (71%) patients. The median and maximum distances of lateral spread for ypT1 tumours were 0 and 4 mm; for ypT2 were 2.5 and 9 mm; and for ypT3 were 4 and 9 mm respectively. CONCLUSION: Lateral tumour spread under normal mucosa adjacent to RMAs is a common finding and extended up to 9 mm in this study. The epicentre for maximum depth of invasion was directly underneath the RMAs in nearly all cases. These data have clinical and technical implications if local excision is to be considered.

Correlation of Clinico-pathological Classification of Hansen's Disease in a South Indian City.

Hansen's Disease (HD) presents itself in different forms depending on the individual's immune status, and based on this Ridley-Jopling classified the disease into five sub-groups. The aim of this study was to evaluate the role of histopathology and bacteriological index (BI) in accurate staging of HD with clinical correlation. Fifty HD patients with clinical diagnosis confirmed by histopathology were included. Patients in reaction and on treatment were excluded. Case records and histopathological slides were viewed and BI was recorded. In 10/50 cases, a diagnosis of HD was made or suspected, but were not clinically classified. In these, histopathology proved useful in diagnosis and classification. Indeterminate HD was the most common histopathological diagnosis (6 cases). The remaining 40 patients, were clinically classified using the Ridley-Jopling classification, as Indeterminate Leprosy (IL) in 10/40 (25%), Tuberculoid Leprosy (TT) 5/40 (12.5%), Borderline Tuberculoid (BT) 16/40 (40%), Borderline Lepromatous (BL) 4/40 (10%) and Lepromatous Leprosy (LL) 5 (12.5%). HD was common in males with male to female ratio of 1.66:1 and affected the younger individuals (maximum in 21 to 30 years). On histopathology BT was the most common type (40%) followed by IL (27.5%), BL (12.5%), TT (10%) and LL (10%). No case of Mid-Borderline (BB) type was diagnosed clinically or histopathologically. Overall concordance between clinical and histopathological diagnosis was 65% (26/40 cases) and for each type was IL = 80%, TT = 20%, BT = 75%, BL = 50% and LL = 60%. Where classification seemed difficult as in cases of BT and BL, II played an important role. The overall concordance between clinical classification and histopathological diagnosis of DO is 65% in this study. Th *discordance that is observed is between BT and TT, the paucibacillary type and BL andILL the multibacillary type and hence the treatment is not affected. Overall, IL was a common diagnosis on histopathology in this study'(11/40 cases and 6/10 cases). If clinically warranted, a repeat deeper punch of skin biopsyrmay be required for a proper categorization of the cases.

Analysis of the effect of baseline detection and early clearance of ct-DNA, on survival outcomes among patients with advanced EGFR-mutant non-small cell lung cancer.

BACKGROUND: To determine if circulating tumor DNA (ct-DNA) dynamics of epidermal growth factor receptor (EGFR) mutation in plasma can identify a subset of patients with EGFR-mutant (EGFR- m) non-small cell lung cancer (NSCLC) with inferior survival outcomes, we analyzed and compared survival outcomes among patients with and without baseline presence and early clearance of EGFR ct-DNA in plasma. MATERIAL AND METHODS: For 66 patients newly dia-gnosed with EGFR- m NSCLC, plasma samples were collected at baseline and 1st response assessment at 12-24 weeks for extraction of ct-DNA. Estimation of ct-DNA (EGFR exons 18, 19, 20 and 21) was done using droplet digital polymerase chain reaction (dd-PCR) on the QX200 ddPCR system (BioRad, USA). Patients with detectable EGFR ct-DNA at baseline (sample 1), with either undetectable or persistent detectable ct-DNA in sample 2 were classified as clearers and non-clearers, respectively. RESULTS: Fifty-three patients received 1st/ 2nd generation EGFR tyrosine kinase inhibitors (TKIs) and 13 received either 3rd generation TKI (osimertinib) or chemotherapy plus gefitinib. The baseline ct-DNA-positive group had more patients with extra thoracic disease (60.4 vs. 48.5%). For the entire cohort, there was no difference in median progression-free survival (PFS) among baseline ct-DNA-negative (13.57 months) vs. ct-DNA-positive patients (12.32 months) (HR 0.74). There was a significant improvement of PFS among early ct-DNA clearers vs. non-clearers (12.32 vs. 9.92 months; HR 0.57). For those treated with 1st/ 2nd generation EGFR TKIs, this improvement in median PFS among early ct-DNA clearers vs. non-clearers was more apparent (11.76 vs. 6.8 months; HR 0.34). CONCLUSIONS: Baseline detection of the presence of ct-DNA of EGFR mutation in plasma was not predictive of first-line PFS, but is associated with extra thoracic disease. Patients with EGFR mutation and persistence of ct-DNA at first follow-up have worse PFS and overall survival (OS) in comparison to those clearing the same in plasma, especially among those treated with 1st/ 2nd generation EGFR TKIs.

Comparison of tube-taping versus a tube-holding device for securing endotracheal tubes in adults undergoing surgery in prone position.

BACKGROUND: Endotracheal tube displacement is one of the leading causes for airway related complications. Endotracheal tube displacement is much more common in the prone position than in the supine position. METHOD: The study population consisted of 120 patients aged between 18-60 years, ASA class 1 and 2, undergoing surgery in the prone position who were randomly allocated into two groups of sixty patients each. The endotracheal tube was secured either with adhesive tape (Group A) or a Thomas tube holder (Group B). The ease of application and removal, effect on caliber of endotracheal tube, amount of displacement of endotracheal tube and also any injuries with either fixation method were studied. RESULT: Both groups were comparable with respect to mean time taken for the application of the fixation device, peak airway pressure change after the application of the fixation device in the supine position and after positioning the patient in the prone position and the time taken for removal of the fixation device. Displacement was significantly larger in group A than in group B. CONCLUSION: Both methods of fixation of the endotracheal tube are clinically useful in the prone position but the Thomas tube holder is more effective than adhesive tape in preventing displacement of endotracheal tube.

Pseudomembranous colitis in a pregnant woman.

Pseudomembranous colitis in association with pregnancy has not been well described in English literature. Recent studies show a drastic increase in the incidence and severity of Pseudomembranous colitis in pregnant women, who were once thought to be at low risk. We report here a case of Pseudomembranous colitis in a young healthy immunocompetent pregnant lady. An early suspicion of this entity with the characteristic appearance of pseudomembranes on colonoscopy and histology confirmed the diagnosis enabling prompt treatment and complete recovery without any serious consequences.

Nonclassical focal nodular hyperplasia of the liver in a chronic alcoholic: a diagnostic dilemma on FNAC.

In a 49 year old male, a chronic alcoholic with hepatomegaly, a subcapsular nodular lesion was detected in the right lobe of the liver. On fine needle aspiration cytology, hepatocellular carcinoma was considered. Excision of the lesion showed features of nonclassical focal nodular hyperplasia with large cell dysplasia that caused the diagnostic dilemma on cytology.

Transluminal closure for NOTES: an ex vivo study comparing leak pressures of various gastrotomy and colotomy closure modalities.

BACKGROUND AND STUDY AIMS: Transluminal closure is fundamental to the safe introduction of natural orifice transluminal endoscopic surgery (NOTES) into humans. Suture, staples, and clips have been used. We aimed to evaluate the acute strength of various gastrotomy and colotomy closure techniques in an ex vivo porcine model by assessing air leak pressures. PATIENTS AND METHODS: The following closure modalities were assessed with at least five samples per arm: conventional open/laparoscopic suturing techniques including full-thickness interrupted sutures, double-layer sutures, and purse-string sutures, as well as endoscopic clips and endoscopic staples. Historical values for transgastric closures with hand-sewn interrupted sutures, endoscopic clips, and a prototype endoscopic suture device were used from our laboratory's prior study. RESULTS: Using Kruskal-Wallis analysis, the overall comparisons were significant ( P = 0.0038 for gastrotomy closure; P = 0.0018 for colotomy closure). Post hoc paired comparisons revealed that the difference between all closure arms versus negative control were significant. Significance could not be established among the various closure arms. However, trends suggested hand-sewn double-layer sutures, endoscopic staples, and both hand-sewn and endoscopically-placed purse-string sutures produced the strongest closures. Furthermore, endoscopic clips appeared sufficient for colotomy closure when ideally placed. CONCLUSIONS: Suture (both hand-sewn and endoscopically deployed) appears to produce the strongest closures in both stomach and colon, with the important caveats that (1) a continuous through-thickness suture track be avoided, such as in the full-thickness closure, or (2) suture holes be buried, such as in the purse-string configuration. When suture tracks are full-thickness, they can serve as leak sites. Staples and clips can produce comparable closures, but only under ideal conditions.

Primary Synovial Sarcoma arising from gingivo-buccal sulcus harbouring SS18-SSX2 positive fusion transcript: The 1st reported case in English literature.

Synovial sarcoma (SS) is a mesenchymal tumour of uncertain histiogenesis that can show dual epithelial and mesenchymal differentiation. Thought to arise predominantly in deep soft tissue of extremities, these sarcomas have shown that they can affect a wide variety of organs and sites, however intraoral mucosal SS is rarely encountered and herein the authors present possibly the second reported case of a young lady presenting with a slow growing tumour arising in the gingivo-buccal sulcus that was reported as Synovial sarcoma on biopsy and subsequently confirmed using molecular studies, tumour demonstrating SS18-SSX2 fusion transcript. Review of the published literature revealed no documented case with molecular fusion transcript making this case the first reported case. This case also highlights the imperative role of immunohistochemistry in tandem with molecular studies to confirm the diagnosis of spindle cell tumours of oral cavity, since squamous cell carcinoma, by far remains the commonest malignancy arising in mucosa lined oral cavity.

Systematic review with meta-analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis.

BACKGROUND: Regulatory requirements for claims of mucosal healing in ulcerative colitis (UC) will require demonstration of both endoscopic and histologic healing. Quantifying these rates is essential for future drug development. AIMS: To meta-analyse endoscopic and histologic placebo response and remission rates in UC randomised controlled trials (RCTs) and identify factors influencing these rates. METHODS: MEDLINE, EMBASE and the Cochrane Library were searched from inception to March 2017 for placebo-controlled trials of pharmacological interventions for UC. Endoscopic and histologic placebo rates were pooled by random effects. Mixed effects univariable and multivariable meta-regression was used to evaluate the influence of patient, intervention and trial-related study-level covariates on these rates. RESULTS: Fifty-six induction (placebo n = 4171) and 8 maintenance trials (placebo n = 1011) were included. Pooled placebo endoscopic remission and response rates for induction trials were 23% [95 confidence interval (CI) 19-28%] and 35% [95% CI 27-42%] respectively, and 20% [95% CI 16-24%] for maintenance of remission. The pooled histologic placebo remission rate was 14% [95% CI 8-22%] for induction trials. High heterogeneity was observed for all outcomes (I2 56.2%-88.3%). On multivariable meta-regression, central endoscopy reading was associated with significantly lower endoscopic placebo remission rates (16% vs 25%; OR = 0.52, [95% CI 0.29-0.92], P = 0.03). On univariable meta-regression, higher histologic placebo remission was associated with concomitant corticosteroids (OR = 1.17 [95% CI 1.08-1.26], P < 0.0001, per 10% increase in corticosteroid use). CONCLUSIONS: Placebo endoscopic and histologic rates range from 14% to 35% in UC RCTs but are highly heterogeneous. Outcome standardisation may reduce heterogeneity and is needed in this field.

Reliability of histologic assessment in patients with eosinophilic oesophagitis.

BACKGROUND: The validity of the eosinophilic oesophagitis (EoE) histologic scoring system (EoEHSS) has been demonstrated, but only preliminary reliability data exist. AIM: Formally assess the reliability of the EoEHSS and additional histologic features. METHODS: Four expert gastrointestinal pathologists independently reviewed slides from adult patients with EoE (N = 45) twice, in random order, using standardised training materials and scoring conventions for the EoEHSS and additional histologic features agreed upon during a modified Delphi process. Intra- and inter-rater reliability for scoring the EoEHSS, a visual analogue scale (VAS) of overall histopathologic disease severity, and additional histologic features were assessed using intra-class correlation coefficients (ICCs). RESULTS: Almost perfect intra-rater reliability was observed for the composite EoEHSS scores and the VAS. Inter-rater reliability was also almost perfect for the composite EoEHSS scores and substantial for the VAS. Of the EoEHSS items, eosinophilic inflammation was associated with the highest ICC estimates and consistent with almost perfect intra- and inter-rater reliability. With the exception of dyskeratotic epithelial cells and surface epithelial alteration, ICC estimates for the remaining EoEHSS items were above the benchmarks for substantial intra-rater, and moderate inter-rater reliability. Estimation of peak eosinophil count and number of lamina propria eosinophils were associated with the highest ICC estimates among the exploratory items. CONCLUSION: The composite EoEHSS and most component items are associated with substantial reliability when assessed by central pathologists. Future studies should assess responsiveness of the score to change after a therapeutic intervention to facilitate its use in clinical trials.

Safety and antitumor activity of recombinant soluble Apo2 ligand.

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.

Transcolonic ventral wall hernia mesh fixation in a porcine model.

BACKGROUND AND STUDY AIMS: A natural orifice transluminal endoscopic surgery (NOTES) approach to ventral wall hernia repair may represent a potentially less invasive alternative to current transabdominal surgical techniques. We aimed to investigate the feasibility of using transcolonic NOTES to deliver hernia repair mesh into the peritoneal cavity, as well as the ability to manipulate composite mesh and secure it to the abdominal wall. METHODS: Five pigs weighing 20 to 25 kg were used in this feasibility study involving two acute and three survival experiments. A prototype mesh delivery system was used to transfer 1.5 - 2-cm x 2.5 - 3-cm pieces of composite hernia mesh into the peritoneal cavity. Neodymium magnets on a prototype control arm were used to help position the mesh by magnetically engaging previously placed endoscopic clips. Transfascial fixation of the mesh with 3-0 monofilament sutures was achieved using a 19-gauge hollow needle, pusher wire, and a suture tag system. RESULTS: Composite hernia mesh was successfully transferred and secured in 5/5 attempts. All three survival animals thrived for 14 days prior to elective sacrifice. At necropsy, the mesh sites were found to be well peritonealized without adhesions. Suture placement through the posterior fascia was confirmed in 10/12 sutures. Of these, four sutures were within the abdominal musculature, and two sutures were through the anterior fascia (transfascial). CONCLUSIONS: Transcolonic delivery, transcutaneous magnetic manipulation, and fixation of composite hernia mesh are technically feasible in a porcine model with animal survival. An effective suturing method that allows consistent anchoring through the anterior fascia would be preferred and may require the development of novel devices.