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Previous studies suggested that the location of the primary tumor in non-small cell lung cancer (NSCLC) is associated with clinical features and prognosis, but results are conflicting. The purpose of this study was to explore tumor location as an independent risk factor of survival for patients with completely resected pathological stage I NSCLC. This was a multicenter retrospective study conducted in Taiwan. Included patients were diagnosed with stage I NSCLC and had undergone primary tumor resection. Variables including tumor location, pathological stage, histological differentiation, and International Association for the Study of Lung Cancer (IASLC) grade were evaluated for predictive ability for disease-free survival (DFS) and overall survival (OS). A total of 208 patients were included, with 123 (59.1%) patients having a primary tumor in the upper and middle lobes. The median duration of follow-up for survivors was 60.5 months. Compared to patients with IASLC Grade 3 disease, patients with Grade 1 disease had significantly longer DFS. Tumor location and IASLC grade were independent predictors for OS in multivariate analysis. Specifically, patients with NSCLC in the lower lobe and patients who are histologically classified as IASLC Grade 3 may have poorer prognosis and require greater attention to improve outcomes.

Objective: This study aims to assess the efficacy of diffusion-weighted (DW) and T1-weighted (T1W) magnetic resonance imaging (MRI) combined with high-resolution computed tomography (HRCT) (together as DW-T1W-CT) in the preoperative evaluation of the presence and extent of cholesteatoma, which helps determine whether a patient is suitable for transcanal endoscopic ear surgery (TEES)., Methods: This retrospective study included 35 patients (18 male and 17 female) aged from 2 to 81 years diagnosed with chronic otitis media with or without cholesteatoma, who had received surgical treatment and a preoperative MRI and HRCT during the period of December 2015 to December 2020 at Cathay General Hospital. We compared the preoperative DW-T1W-CT findings with the intraoperative findings and final pathologic diagnosis. The accurate predictive value was evaluated using the presence of cholesteatoma and its extent., Results: Regarding the efficacy of detecting cholesteatoma, we found a sensitivity of 92% (23/25 cases with cholesteatoma), a specificity of 90% (9/10 cases without cholesteatoma), and an overall accurate predictive value of 91.4% (32/35) by using combined DW-T1W-CT imaging. With regard to evaluating the extent of cholesteatoma, the combined DW-T1W-CT images obtained an accurate predictive value of 84% (21/25 cases of cholesteatoma)., Conclusion: Combined DW-T1W-CT has been proven to be a reliable tool in detecting the presence of cholesteatoma. It is also useful in preoperatively depicting the extent of cholesteatoma, which is crucial for determining whether a patient is suitable for TEES, aiding in surgical planning and patient consultation.

Background: Microglia activation induced by α-synuclein (α-syn) is one of the most important factors in Parkinson's disease (PD) pathogenesis. However, the molecular mechanisms by which α-syn exerts neuroinflammation and neurotoxicity remain largely elusive. Targeting metabotropic glutamate receptor 5 (mGluR5) has been an attractive strategy to mediate microglia activation for neuroprotection, which might be an essential regulator to modulate α-syn-induced neuroinflammation for the treatment of PD. Here, we showed that mGluR5 inhibited α-syn-induced microglia inflammation to protect from neurotoxicity in vitro and in vivo., Methods: Co-immunoprecipitation assays were utilized to detect the interaction between mGluR5 and α-syn in microglia. Griess, ELISA, real-time PCR, western blotting, and immunofluorescence assays were used to detect the regulation of α-syn-induced inflammatory signaling, cytokine secretion, and lysosome-dependent degradation., Results: α-syn selectively interacted with mGluR5 but not mGluR3, and α-syn N terminal deletion region was essential for binding to mGluR5 in co-transfected HEK293T cells. The interaction between these two proteins was further detected in BV2 microglia, which was inhibited by the mGluR5 specific agonist CHPG without effect by its selective antagonist MTEP. Moreover, in both BV2 cells and primary microglia, activation of mGluR5 by CHPG partially inhibited α-syn-induced inflammatory signaling and cytokine secretion and also inhibited the microglia activation to protect from neurotoxicity. We further found that α-syn overexpression decreased mGluR5 expression via a lysosomal pathway, as evidenced by the lysosomal inhibitor, NH 4 Cl, by blocking mGluR5 degradation, which was not evident with the proteasome inhibitor, MG132. Additionally, co-localization of mGluR5 with α-syn was detected in lysosomes as merging with its marker, LAMP-1. Consistently, in vivo experiments with LPS- or AAV-α-syn-induced rat PD model also confirmed that α-syn accelerated lysosome-dependent degradation of mGluR5 involving a complex, to regulate neuroinflammation. Importantly, the binding is strengthened with LPS or α-syn overexpression but alleviated by urate, a potential clinical biomarker for PD., Conclusions: These findings provided evidence for a novel mechanism by which the association of α-syn with mGluR5 was attributed to α-syn-induced microglia activation via modulation of mGluR5 degradation and its intracellular signaling. This may be a new molecular target for an effective therapeutic strategy for PD pathology.

Prevention of colorectal cancer (CRC) depends largely on the detection and removal of colorectal polyps. Despite the advances in endoscopic techniques, there are still a subgroup of polyps that cannot be treated purely by endoscopic approach, which comprise of about 10-15% of all the polyps. These so-called "difficult colorectal polyps" are polyps with large size, morphology, at difficult location, scarring or due to recurrence, which have historically been managed by surgical segmental resection. In treating benign difficult colorectal polyps, we have to balance the operative risks and morbidities associated with surgical segmental resection. Therefore, combined endoscopic and laparoscopic surgery (CELS) has been developed to remove this subgroup of difficult benign polyps. We review the currently use of CELS for difficult benign colorectal polyps which includes laparoscopy-assisted endoscopic polypectomy (LACP), full-thickness laparo-endoscopic excision (FLEX) and colonoscopy-assisted laparoscopic wedge resection (CAL-WR)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jgo.2019.12.11). The series “Current Strategies in Colon Cancer Management” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Journal of Gastrointestinal Oncology. All rights reserved.)

Objectives We examined associations between labor market and health (LM-H) trajectories in the United States between 1988 and 2011 and whether associations differed across macroeconomic expansion/recession periods. Methods Working-age cohorts, derived from the US Panel Study of Income Dynamics, were followed over time to characterize LM-H trajectories. Poisson regression provided relative risks (RR) with robust 95% confidence intervals (CI) for the association between trajectories, adjusting for demographic and socioeconomic variables. Results LM trajectories ending in unemployment (RR 1.7‒2.5 across periods) or inactivity (RR 2.3-3.2) had a greater risk of worsening health trajectories, compared to stable employment. In contrast, RR for individuals returning to work following an intermediary period of unemployment/inactivity were attenuated across most periods. Stable-employed individuals had the highest probability of remaining in good health, whereas trajectories ending in unemployment or inactivity had the lowest probability. These overall relationships were consistent across macroeconomic periods. Conclusions We found strong and consistent relationships between LM-H trajectories across macroeconomic periods. The attenuated (but not eliminated) risk among individuals returning to work following a period of unemployment/inactivity suggests that health outcomes are not only dependent on the LM end-state, but also on the distinct pattern over time.

Objectives: To examine changes in self-reported work conditions over a 10-year time period in Canada, as measured using two comparable cross-sectional surveys conducted in 2002 and 2012., Methods: Population-based data were obtained from the Canadian Community Health Survey. Work conditions (psychosocial work conditions, work hours, work demands, job satisfaction) were measured using the same modules across survey cycles. Regression models provided estimates for trends in work conditions, adjusting for differences in socio-demographic and survey administration characteristics over time., Results: We observed changes in self-reported work conditions across cycles, including higher levels of co-worker/supervisor support and job security; lower levels of psychological demands; and increases in shorter/regular work hours over time. These findings were consistent in both the base and adjusted models. Although skill discretion, decision authority, and job satisfaction improved over time in our base models, these findings were attenuated towards the null in adjusted models. Respondents in 2012 had a greater odds of reporting a physically demanding work environment compared to 2002. Differential time trends were observed by geographic region., Conclusions: Our study found improvements in some self-reported measures of the psychosocial work environment in Canada over time. These changes were not accounted for by socio-demographic or survey administration differences across survey cycles. Despite these overall trends, absolute levels of some work conditions have not changed. Given the relevance of work conditions as a determinant of health, a continued focus on improving all aspects of the work environment should remain a public health priority to improve the health of working-aged Canadians.

Until 1st July 1997, Hong Kong was under the governance of the British Government; therefore, the British system of education was followed. After internship, 7 years of general surgical training is required to obtain registration and fellowship qualifications of the College of Surgeon of Hong Kong and Edinburg. After having become a specialist in general surgery, the surgeon could choose to specialize in colorectal surgery with an additional 3 to 5 years of specialist training in an accredited centre and 6 months of overseas training with subsidies. On the contrary, China has more than 600 medical schools, and students can enroll in different programs to become a medical practitioner. Despite a great discrepancy exists in the quality of teaching and supervision but there are comprehensive regulations governing the accreditation of hospitals, credentialing of operations, medical records, etc. to ensure medical and patient safety. Vast amounts of resources are being invested to strengthen the quality and to advance the technology used in patient care, not only by supporting basic and clinical research but also by providing extra resources to "import" experts and help develop services with clinical excellence. To accomplish this, the aim of the "three fames project" with a 5-year funding of 3 million United States dollar is to invite overseas experts to help build medical teams in specific areas. Due to its huge population (more than 1.3 billion people), China is a country full of potential for development in clinical research, collaboration, knowledge exchange, and the provision of premier medical services.

Laparoscopic repair of ventral incisional hernia with intraperitoneal onlay mesh (IPOM) technique by anti-adhesion mesh has been widely adopted. Due to clinical heterogenicity in location, quantity and size of abdominal incisional hernia, strategy of such repair can be challenging. We hereby present the video of a patient with multiple swiss-cheese hernias in a single long midline incision repaired with double anti-adhesion mesh by IPOM technique. Patient demographics, technical details and clinical tips & tricks are discussed., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: One explanation for why older age is associated with greater duration of wage replacement following a work-related injury may be that older workers sustain more severe injuries and different types of injury compared with their younger counterparts., Aims: To examine the role of injury-related characteristics in explaining the impact of age on wage replacement duration, and whether the relationship between age and wage replacement duration is consistent across injury types and levels of severity., Methods: A secondary analysis of workers' compensation claims in the Australian state of Victoria. In Victoria, only injuries which have accumulated >10 days of wage replacement, or have health care expenditures above a financial threshold, are eligible for compensation. Nested regression models were used to examine the relative contribution of injury-related characteristics to age differences in wage replacement duration., Results: Older age was associated with greater days of wage replacement among men and women, even after adjusting for injury characteristics. Adjustment for differences in injury types and compensation reporting practices resulted in moderate attenuation of the age-duration relationship among men and small attenuation among women. The age-duration relationship was consistent across injury types/severity., Conclusions: The relationship between older age and greater duration of wage replacement is ubiquitous across injuries of different types and severity. Future research is required to understand better why older age is consistently associated with worse compensation outcomes following work-related injury., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: This study aimed to compare the overall and disease specific survivals of patients who underwent laparoscopic and open resection of colorectal cancer in a high volume tertiary center., Methods: Consecutive patients who underwent elective resection for colorectal cancer (open resection, n = 1,197; laparoscopic resection, n = 814) from January 2000 to December 2009 were included. The operative details, postoperative complications, postoperative outcomes, and survival data were collected prospectively. Comparison was made between patients who had laparoscopic and open surgery., Results: The age, gender, medical morbidity, and American Society of Anesthesiologists status were similar in the two groups. Laparoscopic resection was associated with significantly less blood loss and a shorter hospital stay. The operating mortality and morbidity were significantly lower in the laparoscopic group. The qualities of the specimens in terms of the distal resection margin and the number of lymph nodes examined were not inferior in the laparoscopic group. With the median follow-up of 40.3 months, the 5-year overall survival (74.1% vs. 65.5%, p < 0.001) and disease specific survival (81.9% vs. 75.2%, p = 0.002) were significantly better in patients with non-disseminated disease in the laparoscopic group. The operative approach was an independent prognostic factor in the overall (risk ratio 1.36, 95% CI 1.093-1.700, p = 0.006) and disease specific (risk ratio 1.32, 95% CI 1.005-1.738, p = 0.048) survivals in multivariate analysis., Conclusion: Laparoscopic resection for colorectal cancer is associated with more favorable overall and disease specific survivals when compared with open resection in a high volume tertiary center.

Prostate cancer is a major health problem for men in Western societies. Here we report a Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa), in which PTEN was inserted into a DD3-controlled oncolytic viral vector (OV) to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) or, briefly, Ad.DD3.D55-PTEN. The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence, resulting in much higher expression of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN has prostate cancer specific and potent antitumor effect. The tumor growth rate was almost completely inhibited with the final tumor volume after Ad.DD3.D55-PTEN treatment less than the initial volume at the beginning of Ad.DD3.D55-PTEN treatment, which shows the powerful antitumor effect of Ad.DD3.D55-PTEN on prostate cancer tumor growth. The CTGVT-PCa construct reported here killed all of the prostate cancer cell lines tested, such as DU145, 22RV1 and CL1, but had a reduced or no killing effect on all the non-prostate cancer cell lines tested. The mechanism of action of Ad.DD3.D55-PTEN was due to the induction of apoptosis, as detected by TUNEL assays and flow cytometry. The apoptosis was mediated by mitochondria-dependent and -independent pathways, as determined by caspase assays and mitochondrial membrane potential.

Introduction: Both laparoscopic colectomy and application of enhanced recovery program (ERP) in open colectomy have been demonstrated to enable early recovery and to shorten hospital stay. This study evaluated the impact of ERP on results of laparoscopic colectomy and comparison was made with the outcomes of patients prior to the application of ERP., Methods: An ERP was implemented in the authors' center in December 2006. Short-term outcomes of consecutive 84 patients who underwent laparoscopic colonic cancer resection 23 months before (control group) and 96 patients who were operated within 13 months; after application of ERP (ERP group) were compared., Results: Between the ERP and control groups, there was no statistical difference in patient characteristics, pathology, operating time, blood loss, conversion rate or complications. Compared to the control group, patients in the ERP group had earlier passage of flatus [2 (range: 1-5) versus 2 (range: 1-4) days after operation respectively; p = 0.03)] and a lower incidence of prolonged post-operative ileus (6% versus 0 respectively; p = 0.02). There was no difference in the hospital stay between the two groups [4 (range: 2-34) days in control group and 4 (range: 2-23) days in ERP group; p = 0.4)]. The re-admission rate was also similar (7% in control group and 5% in ERP group; p = 0.59)., Conclusions: In laparoscopic colectomy for cancer, application of ERP was associated with no increase in complication rate but significant improvement of gastrointestinal function. ERP further hastened patient recovery but resulted in no difference in hospital stay.

Objective: Totally extraperitoneal (TEP) inguinal hernioplasty for inguinal hernia is associated with less postoperative pain, shorter hospital stays, less chronic pain, and increased patient satisfaction when compared with the open Lichtenstein approach‥ However, only few studies to date have compared conventional with needlescopic TEP hernioplasty for treating unilateral inguinal hernias in adult patients. We report our prospective study that compared the postoperative outcomes of these two approaches over a 2-year period., Methods: From July 2007 to June 2009, a total of 32 patients underwent attempted unilateral needlescopic TEP hernioplasty. All data were prospectively collected and analysed, including demographic features, types of hernia, and postoperative outcome. The results were compared with those of an agematched cohort of 32 patients who underwent conventional TEP hernioplasty in the same period., Results: Needlescopic TEP hernioplasty was successfully performed in 24 patients. The other eight procedures were completed with conventional TEP approaches after changing one or two 5-mm ports. The most common hernia type was Nyhus type III (38/64, 59.3%). There was no significant difference in the mean operative time, hospital stay, and postoperative pain scores between the needlescopic and conventional approaches. There was no major complication detected on the first visit, except seroma formation (9 patients in the needlescopic group and 11 in the conventional group), all of which was resolved with conservative management. No recurrence of hernia was noted in either group during the mean follow-up period of 88.0 weeks., Conclusion: Needlescopic TEP hernioplasty was a feasible technique in selected patients for inguinal hernia repair. Postoperative recovery following both approaches was similar. However, because this was a small cohort study, larger prospective, randomized controlled trials are required to establish the longterm benefit, safety and complications of needlescopic surgery., (Copyright © 2011 Asian Surgical Association. Published by Elsevier B.V. All rights reserved.)

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24), identified by subtraction hybridization in the mid-1990s, is a potent gene therapeutic for cancer. Using a replication-deficient adenovirus as vector, it provokes apoptosis in diverse cancer cells without harming normal cells or tissues. To exploit the anticancer capability of IL-24 to the best, in this study, we generated a novel gene-virotherapy agent MUD55-IL-24, utilizing a replication-competent oncolytic adenovirus MUD55 as the gene delivery vector. It was documented that MUD55-IL-24 exhibited much stronger antitumor activity on gastric carcinoma both in vitro and in vivo, and its safety was comparable to the replication-deficient adenovirus Ad-IL-24. The unique properties of IL-24, including apoptosis induction, antiangiogenesis, and antimigration, were all significantly enhanced in MUD55-IL-24. After looking into the underlying mechanism, we found that intracellular ROS (Reactive Oxygen Species) generation may have caused the induction of apoptosis, mitochondrial dysfunction, and the activation of caspases in MUD55-IL-24-infected SG-7901 cells. Taken together, these results suggest that MUD55-IL-24 may be able to provide a potential strategy for future treatment of human gastric carcinoma.

Objective: This study examined the association between return-to-work (RTW) outcomes and sociodemographic, clinical, and work characteristics among a cohort of injured workers who underwent knee surgery between 2001-2005 in British Columbia, Canada., Methods: Workers' compensation databases were used to identify the retrospective cohort and abstract the study variables. Multinomial logistic regression provided odds ratios (OR) and 95% confidence intervals (95% CI) for the association between RTW (unspecified, partial, full, or non-RTW) and the independent variables., Results: Data was abstracted for 1394 injured workers. Compared to men, women were more likely to have partial RTW (OR 2.55, 95% CI 1.53-4.23) and non-RTW (OR 2.61, 95% CI 1.35-5.03) than full RTW; low income earners were more likely than high income earners to have partial RTW (OR 3.05, 95% CI 1.86-4.99) and non-RTW (OR 4.07, 95% CI 2.19-7.57). Moreover, workers in trade, primary resource, and processing/manufacturing occupations were more likely than those in management occupations to have non-RTW than full RTW by the end of follow-up (OR 2.97, 95% CI 1.32-6.68; OR 9.31, 95% CI 3.41-25.41, and OR 2.71, 95% CI 1.07-6.5, respectively). Surgical and clinical factors were not associated with RTW outcomes., Conclusions: Using population-based data, our study found a link between sociodemographic and work characteristics and the type of RTW outcome following knee surgery for a work-related injury. Women and lower income earners tended not to have full RTW, after controlling for covariates. Workers in physically demanding occupations also tended not to have full RTW, suggesting that factors beyond clinical and surgical characteristics influence disability outcomes. RTW programs need to take into consideration these broader determinants of worker health.

Vascular endothelial cell growth inhibitor (VEGI) is a member of the tumor necrosis factor superfamily and plays an important role in vascular homeostasis. In this study, to investigate the anticancer therapeutic potential of this gene, a secreted isoform of VEGI (VEGI-251) was inserted into a selectively replicating adenovirus with E1B 55 kDa gene deletion (ZD55) to construct ZD55-VEGI-251. We report here that secreted VEGI-251 produced from ZD55-VEGI-251-infected cancer cells potently inhibits endothelial cell proliferation, tube formation in vitro and angiogenesis of chick chorioallantoic membrane in vivo. Additionally, ZD55-VEGI-251 infection leads to a much more severe cytopathic effect than control viruses on several human cancer cell lines, including cervical cancer cell line HeLa, hepatoma cell line SMMC-7721 and colorectal cancer cell line SW620. Further study reveals that the increased cytotoxicity is a result of VEGI-251 autocrine-dependent, mitochondria-mediated apoptosis accompanied by caspase-9 activation, enhanced caspase-3 activation and PARP cleavage. Moreover, ZD55-VEGI-251-treatment of athymic nude mice bearing human cervical and colorectal tumor xenografts markedly suppressed tumor growth. Our findings indicate that the combined effect of antiangiogenesis and apoptosis-induction activity makes the VEGI-251-armed oncolytic adenovirus a promising therapeutic agent for cancer.

Background: Autopsy examination has been the bedrock of western medicine. With the decline in the autopsy rate secondary to the negative psychological impact to the deceased's relatives, the benefits of autopsy have been undermined. Minimally invasive autopsy has been introduced but has not been widely adopted as an alternative to the 'traditional' open approach. This technique not only provides information on the cause of death abut also minimizes the disfigurement induced to the deceased. Our study aims to explore the feasibility and evaluate the accuracy of this technique., Methods: A series of coroner cases ordered for autopsy were examined by a group including an experienced forensic pathologist and two experienced laparoscopic surgeons using thoracoscopic, laparoscopic, endoluminal or endovascular approaches. The procedure was video-recorded and the provisional diagnoses and causes of death were made based on the findings. These findings were subsequently correlated with the full autopsy examination. A few limited clinical post-mortem examinations were also performed with consent from relatives., Results: A total of 22 cases of minimally invasive autopsies were performed from November 2007 to March 2008. The median duration of the procedures was 78.3+/-20.7 min. Thoracoscopies and laparoscopies were performed in 18 patients while additional arterioscopic examination with endoscope was performed in two patients with suspected aortic diseases. Four consented limited clinical autopsies were also performed: two of them involved thoracoscopic biopsies of lung tissues, one was a para-mortem upper endoscopy for the investigation of pathology of the stomach and the other one was laparoscopy for a patient, who died of unexplained acidosis. Comparison with full autopsies showed that the accuracy of the diagnosis was 94.4%, the sensitivity was 90%, the specificity was 100%, the positive predictive value was 100% and the negative predictive value was 88.9%., Conclusion: Minimally invasive autopsy is a feasible approach, yielding accurate findings when compared with conventional autopsies. The former can be a valuable tool for obtaining more valuable information in situations when the next-of-kin of the deceased does not consent to a conventional autopsy., (2009 Elsevier Ireland Ltd. All rights reserved.)

Surgical smoke is the gaseous by-product formed during surgical procedures. Most surgeons, operating theatre staff and administrators are unaware of its potential health risks. Surgical smoke is produced by various surgical instruments including those used in electrocautery, lasers, ultrasonic scalpels, high speed drills, burrs and saws. The potential risks include carbon monoxide toxicity to the patient undergoing a laparoscopic operation, pulmonary fibrosis induced by non-viable particles, and transmission of infectious diseases like human papilloma virus. Cytotoxicity and mutagenicity are other concerns. Minimisation of the production of surgical smoke and modification of any evacuation systems are possible solutions. In general, a surgical mask can provide more than 90% protection to exposure to surgical smoke; however, in most circumstances it cannot provide air-tight protection to the user. An at least N95 grade or equivalent respirator offers the best protection against surgical smoke, but whether such protection is necessary is currently unknown.

Objective: We analyzed circulating TNF-alpha and IL-6 to determine systemic inflammatory responses associated with transvaginal cholecystectomy in a porcine model., Methods: Six female pigs were used for a survival study after transvaginal cholecystectomy (NOTES group) using endoscopic submucosal dissection (ESD) instruments and a single-channel endoscope. Blood was drawn preoperatively and 24 hours and 48 hours postoperatively. Four pigs were used as controls. In addition, laparoscopic cholecystectomy was performed in 2 pigs for laparoscopic control., Results: In all 6 pigs in the NOTES group, no major intraoperative complications occurred. No significant differences were found between control, laparoscopic, and NOTES groups in terms of preoperative IL-6 level (P=0.897) and at 24 hours (P=0.790), and 48 hours postoperatively (P=0.945). Similarly, there was no significant difference in mean preoperative (P=0.349) and mean day 2 postoperative TNF-alpha levels (P=0.11). But a significant increase in day 1 postoperative TNF-alpha levels in the laparoscopic group compared with that in the control and NOTES groups was observed (P=0.049). One limitation of our study is that the sample size was relatively small., Conclusion: NOTES is safe in animal models in terms of anatomical and cellular level changes with minimal systemic inflammatory host responses elicited. Further study needs to be carried out in humans before NOTES can be recommended for routine use.