Inguinal Hernia Formation Research Articles

Functional Investigation and Two-sample Mendelian Randomization Study of Inguinal Hernia Hub Genes Obtained by Bioinformatics Analysis.

Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. This study aims to identify potential gene markers for inguinal hernia and available drugs. Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.

The clinical implications of occult inguinal hernia identified during laparoscopic peritoneal dialysis catheter insertion.

Occult inguinal hernias predispose patients undergoing peritoneal dialysis (PD) to symptomatic inguinal hernia formation causing complications. We conducted a retrospective study to assess the usefulness of routine laparoscopic examination for occult inguinal hernia during PD catheter insertion and the risk profile of occult inguinal hernia according to hernia classification in patients with PD. This study included 79 patients who underwent initial laparoscopic PD catheter insertion between 2021 and 2022. An occult hernia was defined as an internal hernial sac of all sizes that was not detectable on physical examination. The European Hernia Society groin hernia classification was used to describe the hernia type. We investigated the association between event-free survival and occult inguinal hernias in patients undergoing PD. Occult inguinal hernias were diagnosed in 24 (32%) patients. Among these patients, 5 (21%) patients underwent metachronous repair. In patients with L2 occult hernias, the cumulative incidence rates of right and left symptomatic hernias within one year were 100% and 50%, respectively. Multivariate analysis revealed that L2 occult hernias were associated with metachronous hernia repair. The L2 occult inguinal hernia during PD was associated with metachronous repair, suggesting the importance of routine examination of inguinal hernias during laparoscopic PD catheter insertion.

Клініко–анатомічне обґрунтування доцільності одномоментної залобкової простатектомії та симультанної передочеревинної герніопластики у хворих на доброякісну гіперплазію простати та пахвинну грижу

Introduction. Among the complex and unresolved issues of urology and herniology, simultaneous operations for benign prostatic hyperplasia and inguinal hernia occupy a significant place. Inguinal hernias are often found in patients undergoing surgery for benign prostatic hyperplasia, inguinal hernias also often occur after prostatectomy. The presence of an inguinal hernia impairs the quality of life of patients suffering from benign prostatic hyperplasia and carries a potential threat of entrapment. Hernioplasty in a patient with benign prostatic hyperplasia can be complicated by urinary retention in the postoperative period. Therefore, the possibility of one-time simultaneous hernioplasty during prostatectomy for benign prostatic hyperplasia is an urgent issue in both urology and abdominal surgery. The aim of the work: To substantiate the feasibility of using one-moment retropubic prostatectomy and simultaneous pre-peritoneal inguinal hernioplasty from the standpoint of the clinical and anatomical structure of the retropubic space and the back wall of the inguinal canal, as well as to study the factors that affect the occurrence of inguinal hernias after prostatectomy. Research methodology and methods. To substantiate the expediency of retropubic prostatectomy and simultaneous pre-peritoneal hernioplasty, the distance from the middle of the cystic-prostatic junction to the middle of the opening of the direct and indirect inguinal hernias was determined during the operation after removal of the hernia sac from the right and left sides. All simultaneous retropubic prostatectomies and simultaneous hernioplasty were performed from a transverse suprapubic approach, its length varied from 15 to 20 cm depending on the patient's constitution. 36 simultaneous hernioplasty operations were performed on 32 patients (hernioplasty was performed on both sides in 4 cases): an inguinal hernia was detected on the right side in 20 cases, and on the left side in 16 cases. Research results and discussions. The average distance from the middle of the cystic-prostatic junction to the middle of the direct hernia opening was 7.7 ± 1.2 cm on the right side and 7.9 ± 1.1 cm on the left side; the average distance from the middle of the cystic-prostatic junction to the middle of the indirect hernia opening was 11.8 ± 1.4 cm on the right side and 11.6 ± 1.6 cm on the left side. It was established that the operative zones of retropubic prostatectomy and simultaneous pre-peritoneal inguinal hernioplasty are located next to each other, and the maximum distance between them does not exceed 12 cm. The analysis of the literature and our own clinical and anatomical studies made it possible to identify the following anatomical factors of the occurrence of inguinal hernia after prostatectomy: dissection and stretching of the transverse fascia with mirrors, trauma to the muscles of the anterior-lateral wall of the abdomen and a decrease in their tone and sphincter function around the inguinal canal, cicatricial changes in the cystic-prostatic segment with tension in the abdominal part of the vas deferens and expansion of the internal inguinal ring and vaginal process of the peritoneum, straining during urination with an increase intra-abdominal pressure and weakening of the transverse fascia and muscle-aponeurotic structures of the inguinal area, age-related hormonal deficiency. Conclusions. A significant percentage of the formation of inguinal hernias after prostatectomy is associated with anatomical changes that occur after prostatectomy in this area. The close location of the intraoperative zone of prostatectomy to the zone of hernioplasty requires simultaneous pre-peritoneal hernioplasty of not only obvious, but also hidden (occult) inguinal hernias, as well as inguinal hernias in the initial stages of their formation during prostatectomy in patients with benign prostatic hyperplasia and inguinal hernia.

RF03 | PMON300 Sex Hormones, Sex Hormone Binding Globulin, and Gonadotropins in Men with Inguinal Hernias

Abstract Background More than 1 in 4 men will undergo inguinal hernia repair during their lifetime. Age is a significant risk factor for inguinal hernias in men with increased incidence in older age. Sex steroid hormone changes are observed with a higher ratio of serum estradiol (E2) to testosterone (T) as men age. We previously demonstrated that a shift from androgen to estrogen action caused inguinal hernia formation in a transgenic male mouse model with increased estrogen action in lower abdominal muscle tissues. However, age-related changes in serum E2 levels in men are conflicting, as some studies have reported increases but others have noted unchanged or even decreased E2 levels with advancing age. Method: This study was performed on 212 men with inguinal hernias, aged 20 to 90 years, stratified at 10-year intervals of age (20-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90 years). We assessed total T (TT), total E2 (TE2), dehydroepiandrosterone (DHEA), sex hormone-binding globulin (SHBG), and gonadotropins (FSH and LH). Body mass index (BMI) was calculated using height and weight. Results The BMI distribution was balanced for men with inguinal hernias among all age groups. TE2 was low in 23.7%, normal in 65.8%, and high in 10.5% of men 50 years or younger. In contrast, the percentage of patients with high TE2 was increased 2.6-fold in men over the age of 50 (20.1% in low, 52.3% in normal, and 27.6% in high). TT was normal in all men 50 years and younger but was low in 3.5% and normal in 96.5% of men over the age of 50. We found that serum TE2 levels and the ratio of TE2/TT positively correlated with age (p=0.001). In addition, serum TE2 levels were significantly higher in the advanced age groups (71-80 and 81-90 years) than in the young age group (20-40 years). Serum TT levels decreased but did not reach significance in the advanced age groups compared to the young age group. Remarkably the ratio of E2/T was higher in the advanced age groups than in the young age group (20-30 years). Serum DHEA levels in men over the age of 50 were significantly higher than in men 50 years or younger. SHBG levels were higher in men over 70 years than men 50 years or younger (p< 0.01). Serum levels of FSH and LH in men over 60 years were 3-fold greater than in men 50 or younger (p<0.01). Conclusions Our findings suggest a correlation of increased estrogen action in the formation of inguinal hernias at an advanced age. This points to a potential utilization of inhibitors of estrogen synthetase or estrogen antagonists in a subset of elderly inguinal hernia patients with increased circulating estrogen as a non-surgical intervention. Presentation: Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Laparoscopic versus open groin hernia repair in older adults: a systematic review and meta-analysis.

Groin hernia repair is a common surgical procedure and includes both open and laparoscopic techniques. Studies comparing outcomes of laparoscopic versus open groin hernia repair specifically in the geriatric population are lacking. This study compares the outcomes of laparoscopic versus open groin hernia repair techniques in older adults. A literature search was conducted in each of the five selected databases up till June 2021: PubMed (MEDLINE), EMBASE, CINAHL, Cochrane and PsychInfo (OVID). Outcomes measured included but were not limited to total length of hospital stay, mean total operative time, intraoperative complications, post-operative complications such as wound infection, seroma formation, chronic pain, mesh infection and recurrence of inguinal hernia. A total of five articles were included in the final analysis. The length of postoperative hospitalization stay was shorter in patients who underwent laparoscopic hernia repair (95% CI: -1.50 to -0.72; P < 0.01, I2 = 79%). The laparoscopic repair group had a significantly smaller number of patients who sustained postoperative wound infections (95% CI: 0.02 to 0.47; P=0.003, I2 = 0%), and lower incidence of chronic pain (95% CI: 0.14 to 0.37, P < 0.01, I2 = 46%). Analysis of the remaining outcomes did not reveal any statistically significant differences between open and laparoscopic hernia repair. The results of this analysis showed a shorter length of stay, lower wound infection rates and lower chronic pain with laparoscopic groin hernia repair as compared to open repair in older adults. Future prospective studies examining the impact of age on the relationship between surgical approach (open versus laparoscopic) and surgical outcomes are needed.

An estrogen-sensitive fibroblast population drives abdominal muscle fibrosis in an inguinal hernia mouse model.

Greater than 25% of all men develop an inguinal hernia in their lifetime, and more than 20 million inguinal hernia repair surgeries are performed worldwide each year. The mechanisms causing abdominal muscle weakness, the formation of inguinal hernias, or their recurrence are largely unknown. We previously reported that excessively produced estrogen in the lower abdominal muscles (LAMs) triggers extensive LAM fibrosis, leading to hernia formation in a transgenic male mouse model expressing the human aromatase gene (Aromhum). To understand the cellular basis of estrogen-driven muscle fibrosis, we performed single-cell RNA sequencing on LAM tissue from Aromhum and wild-type littermates. We found a fibroblast-like cell group composed of 6 clusters, 2 of which were validated for their enrichment in Aromhum LAM tissue. One of the potentially novel hernia-associated fibroblast clusters in Aromhum was enriched for the estrogen receptor-α gene (Esr1hi). Esr1hi fibroblasts maximally expressed estrogen target genes and seemed to serve as the progenitors of another cluster expressing ECM-altering enzymes (Mmp3hi) and to upregulate expression of proinflammatory, profibrotic genes. The discovery of these 2 potentially novel and unique hernia-associated fibroblasts may lead to the development of novel treatments that can nonsurgically prevent or reverse inguinal hernias.

Impact of Pelvic Bone Anatomy on Inguinal Hernia and the Role of Radiological Pelvimetry.

IntroductionOne of the most prevalent disorders treated by general surgeons is inguinal hernias. Many of the etiological factors that lead to hernia development are unknown. This study looked at the role of pelvic bone anatomy in the development of inguinal hernia. The pubic tubercle's location (as measured by the Radoievitch angle) and its relationship to the formation of inguinal hernia, as well as its function in the pathophysiology of various forms of inguinal hernia, were investigated.Materials and methodsFrom October 2019 to June 2021, a prospective case-control study with 70 individuals over the age of 18 years in each arm was conducted in the Department of General Surgery at our tertiary care institution. Plain digital X-ray radiography of the pelvis, including bilateral hips, was taken in the anteroposterior (AP) view with the patient in the supine position, and the Radoievitch angle and Ami line were measured using suitable measuring instruments. The required information for patients in both groups was tallied and examined in a data sheet.ResultsBetween the case and control groups, there was a statistically significant difference in the mean Radoievitch angles and the mean length of the Ami line (42.46 +/-2.442 degrees vs 40.91 +/-2.547 degrees; p<0.05); (8.54+/-1.059 cm vs 7.27+/-1.034 cm; p<0.05). There was a statistically significant increase in the Radoievitch angle of patients with bilateral hernias compared to unilateral hernias (p-value <0.01), as well as indirect hernias compared to other forms of hernias (p-value <0.05).ConclusionThe probability of having an inguinal hernia was higher when the Fruchaud region was increased, as indicated by a larger Radoievitch angle or a longer Ami line. A low-lying pubic tubercle increased the likelihood of bilateral and indirect inguinal hernias. Pelvimetry is an easy test that should be considered on a routine basis and can be applied accurately in all patients. Surgeons can employ pelvimetry to identify patients who are more likely to benefit from non-mesh repairs.

Risk of Inguinal Hernia Formation after Radical Prostatectomy: A Consequence or Coincidence?

The Post-operation complication is one of the causes of inguinal hernias, but the primary aetiology is still unknown. One of the hypotheses for inguinal hernias is after radical prostatectomy. Inguinal hernia is one of the most common causes of surgery. There are several techniques to repair this problem. However, nowadays there are a variety of articles to explain laparoscopic repair. This disease could be divided into direct and indirect. Indirect hernias usually have a congenital aetiology by open process vaginalis. However, direct hernias are from the inguinal canal’s floor.

Matrix Metalloproteinases (MMP-2) and Tissue Inhibitors of Metalloproteinases (TIMP-2) in Male Inguinal Hernia Patients at Different Ages.

Collagen metabolism, controlled by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), might be related to inguinal hernia formation. It was reported that the incidence of inguinal hernia and the recurrence rate after inguinal hernia repair were higher in the elderly. The objective of the research was to assess the amounts of MMP-2 and TIMP-2 in patients at different ages in order to examine the relationship between age and inguinal hernia occurrence. The research included 40 primary inguinal hernia male patients, and four groups were created: 50-59years old (A group); 60-69years old (B group); 70-79years old (C group); 80-89years old (D group). We got the samples from anterior rectus sheath fascia. Real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry were applied to estimate the levels of MMP-2 and TIMP-2. The MMP-2 amounts in C and D group were statistically higher than control group (P < 0.05), and the TIMP-2 levels in C and D group were statistically lower than control group (P < 0.05). We found a positive correlation between age and expression levels of MMP-2 (r = 0.537, P < 0.001; r = 0.569, P < 0.001) and a negative correlation between age and TIMP-2 in inguinal hernia patients (r = - 0.759, P < 0.001; r = - 0.759, P < 0.001). Increased MMP-2 and reduced TIMP-2 may have some relationships with higher inguinal hernia incidence of the elderly.

Inhibition of Estrogen Signaling Reverses Established Inguinal Hernias

Background: An inguinal hernia occurs when an intestinal loop or fat pushes through a weak spot in the lower abdominal muscle (LAM), causing a painful bulge that has the potential to cause bowel obstruction. Despite a high prevalence in men (~25%), non-surgical approaches are not available to treat this disease. We recently found a critical role of estrogen and estrogen receptor alpha (ERα) in inguinal hernia formation. To examine this further, we use a humanized aromatase mouse model (Aromhum) where all of the male mice develop scrotal hernias as a pre-clinical model to test the first pharmacological intervention for inguinal hernias. These mice are utilized because their skeletal muscle tissue contains aromatase and produces estradiol (E2), which acts via ERα in the LAM stromal fibroblasts and leads to fibrosis and muscle atrophy. Hypothesis: E2-ERα modulation can inhibit and reverse the formation of inguinal hernias in Aromhum mice by reducing LAM fibrosis and atrophy. Results: We tested three types of treatments to inhibit E2-ERα signaling: letrozole, fulvestrant, and raloxifene. Letrozole, an aromatase inhibitor, was shown to inhibit hernia formation and reversed small (150-175 mm2) scrotal hernias (n = 10-15/group, p<0.0001). The LAM tissues also showed a reduction in fibrosis (n = 5-8/group, p = 0.0004) and a concurrent increase in myofiber cross-sectional area (n = 5-8, p=0.0356) compared to placebo-treated mice. Similarly, fulvestrant and raloxifene, E2-ERα antagonists, also inhibited hernia formation (n = 10-15/group). Most interestingly, both drugs reversed large and severe hernias (>200 mm2, n = 10-15/group), accompanied by a decrease in muscle fibrosis and increase in myofiber cross-sectional area (ongoing study, n = 10-11, p<0.0001) compared to placebo mice. The drug-treated mice had lower expression of pro-fibrotic genes such as Mmp3, Emb, Spon2, Timp1, and Tgfb1 in the LAM tissues compared to placebo-treated LAM. Furthermore, we analyzed the differences in extracellular matrix producing genes and muscle regeneration markers between the placebo and drug-treated muscle tissues. Conclusion: We find that inhibition of the E2-ERα signaling pathway can reverse mild or severe inguinal hernias. Successful treatment is accompanied by decreased skeletal muscle fibrosis and reversal of myocyte atrophy. These interventions are promising non-surgical treatment options for patients suffering from severe and recurrent inguinal hernias.

Extraperitoneal versus transperitoneal approach for robot-assisted radical prostatectomy: a contemporary systematic review and meta-analysis.

We aim to evaluate the differences in peri-operative characteristics, surgical complications, and oncological and functional control between the extraperitoneal RARP (EP-RARP) and transperitoneal RARP (TP-RARP). A comprehensive database search was performed up to March 2021 for eligible studies comparing outcomes between EP-RARP versus TP-RARP. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with PROSPERO. A leave-one-out sensitivity analysis was performed to control for heterogeneity and risk of bias. A total of 16 studies were included with 3897 patients, including 2201 (56.5%) EP-RARPs and 1696 (43.5%) TP-RARPs. When compared to TP-RARP, EP-RARP offers faster operative time (MD -14.4min; 95% CI -26.3, -2.3), decreased length of post-operative stay (MD -0.9days, 95% CI -1.3, -0.4), and decreased rates of post-operative ileus (RR 0.2, 95% CI 0.1, 0.7) and inguinal hernia formation (RR 0.2, 95% CI 0.1, 0.5). There were no significant differences in total complications, estimated blood loss, positive surgical margins, or continence at 6months. In this review, EP-RARP delivered similar oncological and functional outcomes, while also offering faster operative time, decreased length of post-operative stay, and decreased rates of post-operative ileus and inguinal hernia formation when compared to TP-RARP. These findings provide evidence-based data for surgical approach optimization and prompts future research to examine whether these findings hold true with recent advances in single-port RARP and outpatient RARP.

Extraperitoneal versus transperitoneal approach for robot-assisted radical prostatectomy: An updated systematic review and meta-analysis.

261 Background: Extraperitoneal RARP (EP-RARP) has recently become a popular surgical approach and is often compared to the transperitoneal RARP (TP-RARP). We conducted a systematic review and meta-analysis of the available literature to evaluate the differences in peri-operative characteristics, oncological and functional control, and surgical complications between EP-RARP and TP-RARP. Methods: A comprehensive search of PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, Google Scholar, and select conference abstract publications was performed for eligible studies comparing outcomes between EP-RARP versus TP-RARP. This was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered with PROSPERO. A leave-one-out sensitivity analyses was performed to control for heterogeneity and risk of bias. Results: A total of 16 studies (three randomized controlled trials, five prospective, and eight retrospective studies) were included with a total pooled population of 3897 patients including 2201 (56.5%) EP-RARPs and 1696 (43.5%) TP-RARPs. When compared to TP-RARP, EP-RARP offers faster operative time (MD: -14.4 minutes; 95% CI: -26.3, -2.3; p = 0.02), decreased length of post-operative stay (MD: -0.9 days, 95% CI: -1.3, -0.4, p &lt; 0.0001), decreased rates of post-operative ileus (RR: 0.2, 95% CI: 0.1, 0.7, p = 0.009) and inguinal hernia formation (RR: 0.2, 95% CI: 0.1, 0.5, p = 0.001). There were no significant differences in total complications, estimated blood loss, positive surgical margins, or urinary continence at 6 months post-RARP. Conclusions: Based on the available evidence, EP-RARP delivered similar oncological and functional outcomes, while also offering faster operative time, decreased length of post-operative stay, and decreased rates of post-operative ileus and inguinal hernia formation when compared to the TP-RARP. These findings provide evidence-based data for surgical approach optimization and prompts future research to examine whether these findings hold true with recent advances in single-port RARP and outpatient RARP.

Mesenteric abscess presents as left iliac fossa mass in postoperative case of inguinal hernia surgery with undescended testis

An abscess is a collection of pus (dead and dying neutrophils plus proteinaceous exudate) that has built up within the tissue of the body. Mesenteric abscess is a rare, usually accounts for small percentage of intra-abdominal abscess after inguinal hernia surgery which is presented as left iliac fossa mass in postoperative period of open inguinal hernia surgery of left side and also presented with undescended testis of left side which is actual cause of formation of inguinal hernia of same side. Late onset mesh infection and post-operative peritonitis are very common in case of open hernia surgery. Intra-abdominal abscess cause significant morbidity and mortality. Surgery disturb the equilibrium between coagulation and fibrinolysis in the abdominal cavity in favour of coagulation system. Diminished fibrin degradation is a common pathway for the formation of abscess. We present a case of 40 years of male came with pain in left iliac fossa and lower abdomen for last 2 months with a swelling at LIF and hypogastric region for last 3 months with a previous history of hernia surgery of left side 2 month back which was diagnosed as mesenteric abscess and treated with exploratory laparotomy under general anaesthesia and abscess was drained.

Incarcerated Amyand hernia: a rare entity

Right sided inguinal hernia containing vermiform appendix in its sac is called as amyand’s hernia. It accounts for ∼1% of all inguinal hernias. It is an intra operative finding during an inguinal hernia repair. A 64 years old male patient came with complains of swelling in the right inguinal region, associated with pain and vomiting. On examination of the right inguinal region there was a tender irreducible swelling palpable. Based on the characteristic finding it was diagnosed clinically as right sided irreducible obstructed inguinal hernia. Ultrasound abdomen was done which was suggestive of right inguinal hernia with herniation of bowel and omentum with features of strangulated/ obstructed hernia. Patient was taken up for right inguinal hernia repair and appendix was noted in the hernial sac intra-operatively. Although occurrence of amyand’s hernia is rare. The attendant surgeon should be vigilant about the presence of it. Preoperative diagnosis of amyand’s hernia is not common because in majority of cases objective of imaging is to exclude conditions that predispose to inguinal hernia formation. The Losanoff and Basson’s criterion is used as a guide for deciding whether to perform appendectomy and type of repair, depend on the clinical scenario.

Matrix Metalloproteinases (MMP-2) and Tissue Inhibitors of Metalloproteinases (TIMP-2) in Patients with Inguinal Hernias.

The development of inguinal hernia might be related with collagen metabolism, which was regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to evaluate the mRNA and protein expression levels of MMP-2 and TIMP-2 in anterior rectus sheath fascia to investigate the function of them in inguinal hernia formation. The study enrolled 48 primary inguinal hernia patients: 32 participants had indirect inguinal hernia and 16 patients suffered direct inguinal hernia. Specimens were taken from the anterior rectus sheath fascia. The amounts of MMP-2 mRNA and TIMP-2 mRNA were evaluated by real-time fluorescence quantitative polymerase chain reaction (RT-PCR), and immunohistochemistry was performed to assess the protein expression of them. The mRNA and protein expression levels of MMP-2 in direct group were significantly higher than those of control group (P < 0.05) and indirect group (P < 0.05), while the expression levels of TIMP-2 in direct group were significantly lower than those of control group (P < 0.05) and indirect group (P < 0.05). The ratio of MMP-2 mRNA/TIMP-2 mRNA in direct group was significantly higher than that of control group (P < 0.05) and indirect group (P < 0.05), and the ratio of indirect group was significantly higher than that of control group (P < 0.05). According to receiver operating characteristic (ROC) curve, MMP-2/TIMP-2 can diagnose direct hernia from controls with area under the curve (AUC) of 0.950 and indirect hernia with AUC of 0.730 effectively. Elevated level of MMP-2 and decreased level of TIMP-2 may play a role in direct inguinal hernia development. The ratio of MMP-2/TIMP-2 may be useful in identification of direct hernia.

SAT-736 Dissecting the Relative Role of Estrogen and Androgen in Fibrosis, Skeletal Muscle Atrophy, and Inguinal Hernia Formation

Introduction: More than one in four men develop symptomatic inguinal hernia, and hernia repair is the most commonly performed general surgical procedure in the US. Despite its prevalence, the molecular mechanisms causing inguinal hernia remain unclear. Aromatase, the key enzyme for the conversion of testosterone (T) to estradiol (E2), is present in human but not mouse skeletal muscle tissue. We recently demonstrated that robustly increased local E2 levels in lower abdominal muscle (LAM) tissue and decreased circulating T levels were associated with fibrosis and myocyte atrophy in LAM tissue, leading to severe scrotal (inguinal) hernia formation in a humanized aromatase transgenic mouse model (Aromhum) with a high LAM human aromatase expression. To further determine the relative role of estrogen and androgen in the development of inguinal hernia, we generated a novel mild Aromhum mouse model with lower LAM aromatase expression compared with the severe model. Methods: Mild Aromhum mice were followed for 6 months to determine hernia incidence and measure hernia size (n=30). We treated mild Aromhum mice with the aromatase inhibitor, letrozole (n=12) for 12 weeks. Circulating and LAM E2 levels in mice were measured using mass spectrometry. LAM tissue fibrosis and myocyte size were determined by Masson’s trichrome staining and H&E staining, respectively. Results: The mild Aromhum mice contain a single copy of the human aromatase genomic fragment with a truncated regulatory region, giving rise to significant but mildly elevated LAM E2 levels (2.5-fold) at 15 weeks of age. Interestingly, these mice maintain normal circulating T levels. Furthermore, we show that mildly increased LAM E2 without decreased circulating T levels cause hernia formation in about 88% of mild Aromhum mice in contrast to 100% hernia formation in mice containing the full-length human aromatase regulatory region (severe Aromhum model), suggesting that higher LAM estrogen and low serum T levels contribute to this severe phenotype. Treatment with an aromatase inhibitor restores LAM E2 levels to normal levels and completely prevents inguinal hernia formation in the mild Aromhum mice. In LAM fibroblasts of mild Aromhum mice, we find very high levels of estrogen receptor-α expression, which possibly mediates estrogen-induced hernia formation. Conclusion: Taken together, our findings from the mild Aromhum mouse model suggest that lower levels of estrogen excess in LAM are the primary driver of muscle atrophy and hernia formation because this mouse model do not exhibit circulating T deficiency. Our findings will constitute a starting point for dissecting the relative roles of estrogen and androgen action in inguinal hernia development. This has the potential to facilitate drug development to prevent and treat hernias, especially recurrent hernias after primary hernia repairs in vulnerable populations such as elderly men.

SAT-747 A Prospective Non-surgical Treatment for Inguinal Hernias

BACKGROUND: Inguinal hernias are a widespread public health issue and typically diagnosed in one-fourth of all men. Despite hernia repair being the most commonly performed surgery in the US, the mechanisms causing this disease are currently unknown. We previously developed a mouse model that expresses the human aromatase gene (Aromhum) wherein all male mice develop inguinal hernias. We further showed that high production of estradiol by aromatase in the lower abdominal muscle (LAM) via binding to estrogen receptor caused increased fibroblast proliferation and muscle atrophy which leads to inguinal hernia formation (1). Hypothesis: Disruption of estrogen signaling via ablation of estrogen production using an aromatase inhibitor or inhibition of estrogen receptor by an estradiol antagonist can prevent or reverse the formation of inguinal hernias. Results: We previously demonstrated that aromatase inhibitor, letrozole, completely prevented the formation of inguinal hernias in Aromhum mice (1). Here we show that ER-dependent estradiol antagonist fulvestrant can also prevent LAM tissue fibrosis, muscle atrophy and hernia formation in Aromhum mice (n=4, p=0.0007). WT littermates did not show hernia formation with or without fulvestrant treatment (n=4). Furthermore, we demonstrate that aromatase inhibitor letrozole can reverse mild to moderate size of hernia (150-160 mm2), while placebo-treated mice had progressively enlarged hernias (n=7, p=0.04). We subsequently show a reduction in muscle fibrosis and a restoration of myocyte size in Aromhum mice with letrozole treatment. Conclusion: Estrogen produced as a result of aromatase expression in estrogen-sensitive LAM tissue stimulates the proliferation of estrogen receptor-expressing fibroblasts, fibrosis, muscle atrophy, and hernia formation. Ablation of estrogen production or its signaling not only completely prevents this phenotype but also reverses mild to moderate-sized hernias. Our findings pave the pathway for developing the first potential preventive and therapeutic pharmacological approach for combating recurrent inguinal hernias in elderly men through modulation of estrogen signaling in abdominal muscle tissue. Reference: (1) Zhao H, et al.,PNAS. 2018 Oct 30;115(44):E10427-36.

A network analysis revealed the essential and common downstream proteins related to inguinal hernia.

Although more than 1 in 4 men develop symptomatic inguinal hernia during their lifetime, the molecular mechanism behind inguinal hernia remains unknown. Here, we explored the protein-protein interaction network built on known inguinal hernia-causative genes to identify essential and common downstream proteins for inguinal hernia formation. We discovered that PIK3R1, PTPN11, TGFBR1, CDC42, SOS1, and KRAS were the most essential inguinal hernia-causative proteins and UBC, GRB2, CTNNB1, HSP90AA1, CBL, PLCG1, and CRK were listed as the most commonly-involved downstream proteins. In addition, the transmembrane receptor protein tyrosine kinase signaling pathway was the most frequently found inguinal hernia-related pathway. Our in silico approach was able to uncover a novel molecular mechanism underlying inguinal hernia formation by identifying inguinal hernia-related essential proteins and potential common downstream proteins of inguinal hernia-causative proteins.

The Role of System connective tissue dysplasia in the Formation of hernia Inguinal Area

Relevance. Despite advances in the treatment of inguinal hernias are still being discussed, the issues of post-operative wound complications and disease recurrence. The inclusion in the list of risk factors for complicated postoperative course of systemic connective tissue dysplasia will allow a new look at the mechanisms of herniation in the groin area and develop morphologically adapted methods of surgical treatment.&#x0D; Objective. Study the characteristics of connective tissue dysmorphogenesis at hernia protrusions in the inguinal region. &#x0D; Results. In the main group absolutely reliable connection with all possible variants of hernia disease in the inguinal region possessed 6 (12 %) the morphological predictors, namely: dystonia dysfunction, curvature of the spine, hallus valgus, hypermobility joints, varicose disease of the lower limb and hemorrhoids. The curvature of a backbone and hyper mobility of joints occurred among manifestations of a dismorfizm at patients of control group.&#x0D; The area of electromyograms at reduction of muscles forming the torn down hernia the inguinal interval, on 20 % inferior area electromyograms reduction of similar muscles on contralateral from inguinal hernia to the side and on 61,4 % of area electromyograms contraction of the groin muscles of the control group patients. In a smaller proportion, but with similar characteristics reduced groups of lateral muscles, which is considered by us as local functional predictors of the implementation of systemic connective dysplasia in the hernia disease of the inguinal region.&#x0D; The density of the collagen fibers in the dermis of patients with inguinal hernias was 75.6 + 1.9%, which is 12,3 % lower than the result of such collagen metrics index of patients of the control group. Intensity of coloring of micropreparations of dermis of patients of control group was at the level of 36,33 + 2,1, that on 1,8 times less than this index in patients of the basic group. &#x0D; Conclusions. Thus, results of histology confirm reliability of the revealed morphological and local functional prerequisites of formation of inguinal hernias at connective dysplasia.

The Clinical Study: Impact of Benign Prostate Hyperplasia on the Inguinal Hernia Formation

The aim of this study was to explore impact of Benign Prostate Hyperplasia on inguinal hernia formation in elder men through a clinical trial among Benign Prostate Hyperplasia of the elderly patients who undergo inguinal hernia surgery. Three routine preoperative examinations to determine the extent of prostate hyperplasia were conducted on 368 elderly patients who were admitted for inguinal hernia surgery (Experimental group) and on 203 other elderly patients who underwent other nonemergency surgeries (Control group) from January of 2010 to December of 2013. The results of IPSS score, the prostate size, and the urine residual volume obtained from the patients of the Experimental group indicated statistically significant differences from those of the Control group. It was concluded that voiding difficulty caused by Benign Prostate Hyperplasia is a significant reason for elderly male patients to develop into inguinal hernia. It is important to have routine prostate examinations required for elderly male patients with the diagnosis of inguinal hernia.