Comparison of mesh repair and suture repair for the treatment of incarcerated femoral hernia: a retrospective, single-center study.

BACKGROUND: Femoral hernias often present with incarceration or strangulation that requires emergency surgery. However, recommendations vary regarding optimal approaches for incarcerated femoral hernia. The aim of this study is to compare clinical efficacy between mesh repair and suture repair for the treatment of incarcerated femoral hernia. METHODS: Retrospective, single-center analysis of the clinical data from 48 patients with incarcerated femoral hernia, including 16 patients who underwent mesh repair (mesh repair group) and 32 patients who underwent traditional suture repair (suture repair group). RESULTS: The mean age, body mass index, incarceration duration, hernia sac size, operation duration, and the rates of postoperative incision infection, recurrence, chronic pain, and mortality were not significantly different between the suture repair and mesh repair groups (P > 0.05 for all). In contrast, the female/male ratio; the rates of bowel obstruction, coexisting diseases, and nighttime operation; and the American Society of Anesthesiologists grade were higher and the rate of prophylactic antibiotic use and the mean cost of hospitalization were lower in the suture repair group than in the mesh repair group (P < 0.05 for all). CONCLUSION: The surgical approach should be chosen based on the patient's condition. Mesh repair for the emergency treatment of incarcerated femoral hernia is safe and effective, whereas suture repair is suitable for elderly patients, those with more coexisting diseases, and those with limited life expectancy.

Supramolecular Chemotherapy: Host-Guest Complexes of Heptaplatin-Cucurbit[7]uril toward Colorectal Normal and Tumor Cells.

Supramolecular chemotherapy is a strategy that is currently used to improve the therapeutic efficacy of traditional chemotherapy while mitigating side effects. Heptaplatin, a platinum chemotherapeutic antitumor drug in colorectal tumors, is traditionally used in the clinic. However, its side effects and low efficiency in killing tumors remain unresolved. Herein, a facile supramolecular chemotherapy platform on account of the host-guest chemistry between cucurbit[7]uril and the commercially available heptaplatin was studied. At pH 7.4, heptaplatin showed a strong binding to the cucurbit[7]uril nanocarrier by 1H NMR, whose Ka was (1.38 ± 0.06) × 106 M-1 by isothermal titration calorimetry (ITC). At pH 6.0 in a tumor microenvironment, overexpressed spermine can exchange competitively heptaplatin from heptaplatin-CB[7]. This supramolecular complex achieved higher antitumor activity on colorectal tumor cells and lower cytotoxicity than the drug alone on colorectal normal cells. Furthermore, the antitumor mechanisms of supramolecular complex were investigated by apoptosis, cell cycle, and spermine synthase. It was found that heptaplatin-CB[7] consumed more colorectal tumorous intracellular spermine by the spermine synthase assay (413.85 ± 0.004 pg/mL); hepataplatin-CB[7] caused early apoptosis (87.73%) of colorectal tumor cells; heptaplatin-CB[7] induced an inhibitory response in the G1 phase of the tumor cell cycle. These findings demonstrated that heptaplatin-CB[7] had higher antitumor activity toward human colorectal tumor cells but lower cytotoxicity toward human colorectal normal cells. It is expected to promote the supramolecular chemotherapy and translational development of the nanocomplex into the clinical field.

Subxiphoid top-down endoscopic totally preperitoneal approach (eTPA) for midline ventral hernia repair.

PURPOSE: Midline abdominal wall hernia repair is among the most common surgical interventions performed worldwide. However, the optimal surgical technique remains controversial. To overcome the disadvantages of both open and transabdominal procedures, we developed a totally endoscopic preperitoneal approach (eTPA) with placement of a large mesh. METHODS: From December 2019 to October 2020, 20 consecutive patients with small to medium-sized midline ventral hernias underwent repair using a completely preperitoneal subxiphoid top-down approach. The preperitoneal space was entered directly below the xiphoid, and careful endoscopic development of the plane between the peritoneum and posterior sheath of the rectus fascia was then performed behind the linea alba. The hernia sac and its contents were identified and reduced. The hernia defect was closed with sutures, and a mesh with an adequate high defect: mesh ratio was placed in the newly created preperitoneal space. RESULTS: Twenty patients were enrolled in this study, including 14 with primary umbilical hernias, 4 with primary epigastric hernias, and 2 with recurrent umbilical hernias. 15 patients suffered from a mild concomitant diastasis recti. All operations were successfully completed without conversion to open repair. The mean operative time was 105.3 min (range, 60-220 min). Postoperative pain was mild, and the mean visual analog scale score for pain was 1.8 on the first postoperative day. The average postoperative hospital stay was 1.8 days (range, 1-4 days). One patient developed a minor postoperative seroma, but it had no adverse impact on the final outcome. No patients developed recurrence during the 3- to 10-month follow-up period. CONCLUSIONS: The subxiphoid top-down totally endoscopic preperitoneal approach (eTPA) technique is feasible and effective. It may become a valuable alternative for the treatment of primary small- (defect size < 2 cm) and medium-sized (2-4 cm) midline ventral hernias, particularly in presence of a concomitant diastasis recti.

Urogenital fascia anatomy study in the inguinal region of 10 formalin-fixed cadavers: new understanding for laparoscopic inguinal hernia repair.

PURPOSE: To investigate the urogenital fascia (UGF) anatomy in the inguinal region, to provide anatomical guidance for laparoscopic inguinal hernia repair (LIHR). METHODS: The anatomy was performed on 10 formalin-fixed cadavers. The peritoneum and its deeper fascial tissues were carefully dissected. RESULTS: The UGF's bilateral superficial layer extended and ended in front of the abdominal aorta. At the posterior axillary line, the superficial layer medially reversed, with extension represented the UGF's deep layer. The UGF's bilateral deep layer medially extended beside the vertebral body and then continued with the transversalis fascia. The ureters, genital vessels, and superior hypogastric plexus moved between both layers. The vas deferens and spermatic vessels, ensheathed by both layers, moved through the deep inguinal ring. From the deep inguinal ring to the midline, the superficial layer extended to the urinary bladder's posterior wall, whereas the deep layer extended to its anterior wall. Both layers ensheathed the urinary bladder and extended along the medial umbilical ligament to the umbilicus and in the sacral promontory, extended along the sacrum, forming the presacral fascia. The superficial layer formed the rectosacral fascia at S4 sacral vertebra, and the deep layer extended to the pelvic diaphragm, terminating at the levator ani muscle. CONCLUSION: The UGF ensheaths the kidneys, ureters, vas deferens, genital vessels, superior hypogastric plexus, seminal vesicles, prostate, and urinary bladder. This knowledge of the UGF's anatomy in the inguinal region will help find correct LIHR targets and reduce bleeding and other complications.

Endoscopic totally extraperitoneal approach (TEA) technique for primary ventral hernia repair.

BACKGROUND: Up to now the totally extraperitoneal (TEP) technique is limited to the treatment of inguinal hernias. Applying this anatomical repair concept to the treatment of other abdominal wall hernias, we developed an endoscopic totally extraperitoneal approach (TEA) to treat primary midline ventral hernias, including umbilical and epigastric hernias, in which for mesh placement, an anatomical space is developed between the peritoneum and the posterior rectus sheath in the ventral part of the abdominal wall (preperitoneal space). METHODS: Between September 2017 and December 2019 according to the selection criterions, 28 consecutive primary midline ventral hernias were repaired using TEA. After extensive endoscopic development of the midline extraperitoneal plane, which was started in the suprasymphysic area, and reduction of the hernia sac, the hernia defect was closed and a large mesh was placed in the preperitoneal position to enforce the anterior abdominal wall. RESULTS: All operations were successfully performed without conversion to open surgery. The mean operation time was 103.3 min (range 85-145 min). Patient-reported postoperative pain was qualitatively mild with a mean pain visual analogue scale score of 1.9 on postoperative day 1. The average hospital stay was 1.9 days (range 1-3 days). Three patients developed minor complications and were treated with no long-term adverse effects. Readmissions within 30 days or hernia recurrences were not observed with a mean follow-up period of 18 months (range 10-27 months). CONCLUSION: In selected cases, TEA is a safe and feasible minimally invasive alternative in treating primary ventral hernias. This technique preserves the anatomical and physiological structure of the abdominal wall and may significantly reduce trauma and postoperative complications. Additionally, anti-adhesion-coated meshes and fixation tackers are not required, thus being cost-effective. Further studies are necessary to proof the true clinical efficacy in comparison to well-known alternative techniques.

Totally endoscopic sublay (TES) repair for midline ventral hernia: surgical technique and preliminary results.

BACKGROUND: The Rives-Stoppa procedure is used for ventral hernia repair but requires a large midline incision. This report describes a new, totally endoscopic approach to the retromuscular plane, corresponding to a reversed totally extraperitoneal procedure, to perform sublay repair of primary and secondary ventral hernias. This totally endoscopic sublay (TES) repair is described in detail, and its safety and efficacy were evaluated. METHODS: In this prospective study, we assessed 26 consecutive primary and secondary epigastric midline ventral hernias that were repaired between July 2017 and July 2018 using the TES procedure. A large mesh was placed in the retrorectus position using this minimally invasive approach. Indications for this procedure include umbilical, epigastric, incisional hernias, and rectus diastasis. RESULTS: All TES procedures were successfully performed without conversion to an open operation. The mean operative time was 106.6 ± 29.1 min (range 75-205), with average mesh area of 318.8 cm2 for an average defect area of 26.5 cm2. Postoperative pain was mild, and the mean visual analog scale (VAS) under physical stress (e.g., climbing stairs) was 2.4 at the third postoperative day. The average postoperative hospital stay was 2.8 ± 0.8 days (range 2-5). Two patients developed postoperative seroma, with no final adverse effect. No recurrence nor readmissions within 30 days was observed during a mean follow-up of 9.2 ± 4.4 months. CONCLUSIONS: Initial experiences with this technique show that the TES procedure is safe and reliable, requires no specific instruments, and is highly reproducible. There is no need for an expensive anti-adhesion mesh or fixation device, making it cost-effective.

Single-incision laparoscopic transabdominal preperitoneal repair in the treatment of adult female patients with inguinal hernia.

BACKGROUND: Women have a 3% lifetime chance of developing an inguinal hernia, which is not as common in men. Due to its cosmetic benefits, single-incision laparoscopic transabdominal preperitoneal (SIL-TAPP) inguinal hernia repair is becoming increasingly popular in the management of inguinal hernia in women. However, there are no studies comparing the safety and applicability of SIL-TAPP repair with conventional laparoscopic transabdominal preperitoneal (CL-TAPP) inguinal hernia repair for the treatment of inguinal hernia in women. AIM: To compare the outcomes of SIL-TAPP and CL-TAPP repair in adult female patients with inguinal hernia and to estimate the safety and applicability of SIL-TAPP repair in adult female inguinal hernia patients. METHODS: We retrospectively compared the clinical information and follow-up data of female inguinal hernia patients who underwent SIL-TAPP inguinal hernia repair and those who underwent CL-TAPP inguinal hernia repair at the Affiliated Hospital of Nantong University from February 2018 to December 2020 and assessed the long-term and short-term outcomes of both cohorts. RESULTS: This study included 123 patients, with 71 undergoing SIL-TAPP repair and 52 undergoing CL-TAPP repair. The two cohorts of patients and inguinal hernia characteristics were similar, with no statistically meaningful difference. The rate of intraoperative inferior epigastric vessel injury was lower in patients in the SIL-TAPP cohort (0, 0%) than in patients in the CL-TAPP cohort (4, 7.7%) and was significantly different (P < 0.05). In addition, the median [interquartile range (IQR)] total hospitalization costs were significantly lower in patients in the SIL-TAPP cohort [$3287 (3218-3325)] than in patients in the CL-TAPP cohort [$3511 (3491-3599)]. Postoperatively, the occurrence rate of trocar site hernia was lower in the SIL-TAPP cohort (0, 0%) than in the CL-TAPP cohort (4, 7.7%), and the median (IQR) cosmetic score was significantly higher in the SIL-TAPP cohort [10 (10-10)] than in the CL-TAPP cohort [9 (9-10)]. CONCLUSION: SIL-TAPP repair did not increase the incidence of intraoperative and postoperative complications in female inguinal hernia patients. Moreover, female inguinal hernia patients who underwent SIL-TAPP repair had a lower probability of trocar site hernia and inferior epigastric vessel injury than female inguinal hernia patients who underwent CL-TAPP repair. In addition, female inguinal hernia patients who underwent SIL-TAPP repair reported a more aesthetically pleasing postoperative abdominal incision. Therefore, SIL-TAPP repair is a better option for the treatment of inguinal hernias in women.

Insulin-like growth factor 1 receptor promotes the growth and chemoresistance of pancreatic cancer.

BACKGROUND: Insulin-like growth factor 1 receptor (IGF1R) plays important roles in the progression of pancreatic cancer. However, the underlying mechanism remains unclear. AIMS: The purpose of this study was to investigate the effects of IGF1R knockdown on the proliferation, apoptosis and chemosensitivity of pancreatic cancer cells, and explore the possible mechanisms. METHODS: Pancreatic cancer cells expressing IGF1R shRNA were established, and the cell proliferation, colony formation, and chemosensitivity to gemcitabine were examined in vitro. The activation of AKT and NF-κB was detected by Western blot analysis and luciferase assay, respectively. Xenograft mice models were established to evaluate the in vivo anti-tumor effects of IGF1R knockdown. RESULTS: IGF1R knockdown notably inhibited pancreatic cancer cell proliferation and colony formation, induced apoptosis, and inhibited xenograft tumor growth. Moreover, IGF1R knockdown significantly enhanced chemosensitivity to gemcitabine in pancreatic cancer cells, and this was correlated with the inhibition of PI3K/AKT and NF-κB pathways. CONCLUSIONS: IGF1R knockdown suppresses tumor growth and enhances chemosensitivity in pancreatic cancer via the inhibition of PI3K/AKT and NF-κB pathways, and is a promising approach to overcome the chemoresistance of pancreatic cancer.

Suppression of the epidermal growth factor receptor inhibits epithelial-mesenchymal transition in human pancreatic cancer PANC-1 cells.

BACKGROUND: Aberrant expression of epidermal growth factor receptor (EGFR) has been detected in pancreatic cancer; however, the mechanisms of EGFR in inducing pancreatic cancer development have not been adequately elucidated. The objective of this study was to determine the role of EGFR in mediating epithelial-mesenchymal transition (EMT) in pancreatic cancer cells. METHODS: Pancreatic cancer cell line PANC-1 was transfected with small interfering RNA of EGFR by use of a lentiviral expression vector to establish an EGFR-knockdown cell line (si-PANC-1). PANC-1 cells transfected with lentiviral vector expressing negative control sequence were used as negative control (NC-PANC-1). Scratch assay and transwell study were used to analyze cell migration and invasion. Real-time PCR and Western blotting were used to detect the expression of EMT markers E-cadherin, N-cadherin, vimentin, and fibronectin and transcription factors snail, slug, twist1, and sip1 in PANC-1, NC-PANC-1, and si-PANC-1 cells. Immunofluorescent staining with these antibodies and confocal microscopy were used to observe their cellular location and morphologic changes. RESULTS: After RNA interference of EGFR, the migration and invasion ability of si-PANC-1 cells decreased significantly. The expression of epithelial phenotype marker E-cadherin increased and the expression of mesenchymal phenotype markers N-cadherin, vimentin, and fibronectin decreased, indicating reversion of EMT. We also observed intracellular translocation of E-cadherin. Expression of transcription factors snail and slug in si-PANC-1 cells decreased significantly. CONCLUSION: Suppression of EGFR expression can significantly inhibit EMT of pancreatic cancer PANC-1 cells. The mechanism may be related with the down-regulation of the expression of transcription factors snail and slug.

[Effects and mechanisms of combined suppression of epidermal growth factor receptor and hedgehog signaling on proliferation in pancreatic cancer cells].

OBJECTIVE: To explore the synergistic effects on proliferation and apoptosis by targeted suppression of epidermal growth factor receptor (EGFR) in combination with blockade of Hedgehog signaling pathways in pancreatic cancer cells and examine the synergistic mechanism of Hedgehog and EGFR signaling pathways. METHODS: The sequences of RNA interference targeting EGFR gene were designed, synthesized and cloned into the pFU-GW-RNAi vector. And a stable transfection cell line was obtained by transfecting the human Panc-1 cells with lentivirus. The expressions of Shh and Gli1 were tested by real-time polymerase chain reaction (PCR). The antiproliferative effect was examined by the assays of colony formation and methyl thiazolyl tetrazolium (MTT). Fluorescence activated cell sorter (FACS) was applied to assay the apoptotic rate in all experimental groups. Western blot was applied to detect the phosphorylation levels of ERK and AKT.In vivo nude mice tumorigenicity model was used to test the effect of growth inhibition. RESULTS: The RNAi technology with lentivirus could restrain the expression of EGFR gene. After the blocking of EGFR and Hedgehog signaling pathways by RNAi silencing, the chemosensitivity to cyclopamine significantly increased in human pancreatic cancer cells. The half-inhibitory concentration (IC 50) of cyclopamine declined from (2.978 ± 0.336) to (1.698 ± 0.057) µmol/L (P < 0.05). The prophase apoptotic rate of co-treated group was as high as 38.75% and it was significantly higher than the RNAi silencing EGFR (17.65%) and control groups (3.02%) (P < 0.05). The results of tumor xenografts assay showed that the tumor volume of co-treated group (394.8 ± 87.5 mm(3)) was significantly lower than that of simple EGFR RNAi (594.7 ± 86.1 mm(3)) and single cyclopamine treated group (771.3 ± 82.9 mm(3)); the combination treatment could also produce obviously synergistic antiproliferative effect in colony formation assays. After RNAi silencing EGFR, the phosphorylation levels of ERK and AKT decreased significantly versus the control group. Further reduction was obtained with the combined use of cyclopamine in the co-treated group. CONCLUSION: The blocking of EGFR and Hedgehog signaling pathways by RNAi silencing may further inhibit cell proliferation and increase apoptosis in vivo and in vitro in human pancreatic cancer cells. The synergism of Hh and EGFR signaling pathways may be correlated with the phosphorylation levels of ERK and AKT.

Totally endoscopic sublay/extraperitoneal Sugarbaker mesh repair for parastomal hernia.

INTRODUCTION: Shared consensus is that a nonslit-mesh-based laparoscopic repair technique is the optimal treatment principle for parastomal hernia (PSH). MATERIALS AND SURGICAL TECHNIQUE: An 81-year-old female parastomal hernia patient who had a previous history of laparoscopic abdominoperineal resection presented for surgical treatment. We performed a novel totally endoscopic sublay/extraperitoneal Sugarbaker mesh repair (TES-Sugarbaker) for this disease. The mesh was deployed in the sublay/extraperitoneal plane in a Sugarbaker configuration. DISCUSSION: TES-Sugarbaker repair for parastomal hernia is technically feasible, it requires no anti-adhesive coated mesh and less traumatic fixation, then reduces the mesh-related complication and postoperative pain, making it more cost effective. The present described case represents an early attempt to perform endoscopic sublay/extraperitoneal mesh repair for PSH.

Internal Ring Defect Closure Technique in Laparoscopic Mesh Hernioplasty for Indirect Inguinal Hernia.

PURPOSE: The best way to reduce seroma formation after laparoscopic indirect hernia repair is debated. We noticed that internal ring defect closure in laparoscopic mesh hernioplasty could provide promising outcomes with an effect on diminishing seroma formation. We introduce our closure technique and report our experience. METHODS: This prospective study was conducted from May 2019 to May 2021. Patients with European Hernia Society classification L3 indirect or scrotal hernia were recruited and underwent laparoscopic transabdominal patch plasty (TAPP). Hernia defect closure was performed before mesh deployment. The primary outcomes were seroma formation, postoperative pain, and hernia recurrence. Perioperative data and postoperative complications were also recorded. RESULTS: Consecutive 77 patients with 89 indirect hernias (including 51 scrotal hernias) were recruited in two regional tertiary hospitals. All operations were successful without open conversion. The mean size of the hernia defect was 3.7 ± 0.5 cm (range, 2.5-5.0 cm). The mean operative time for each hernia repair (peritoneum to peritoneum) was 48.3 ± 10.8 min (range, 33-72 min), and the mean time required for internal ring closure was 6.7 ± 2.2 min (range, 4-10 min). Intraoperative bleeding was minimal. The mean visual analog scale pain score at rest on the first postoperative day was 2.2 (range, 1-4). The average postoperative length of hospital stay was 18 h (range, 14-46 h). During a mean follow-up period of 9.4 months (range, 3-23 months), no hernia recurrence or chronic pain were noted. Seroma formation was detected on six sides of unilateral hernias (6.7%) on postoperative day 7, with a mean volume of 45.8 ml (range, 24-80 ml). All seromas were mild and resolved spontaneously within 3 months, with no need for evacuation or other treatment and without major impact on the final outcome. CONCLUSIONS: Defect closure in laparoscopic mesh hernioplasty for large indirect hernias is safe and feasible and can significantly reduce postoperative seroma formation and relative complications. This approach is recommended in large indirect or scrotal hernia repair.

[Regulatory mechanisms of Hedgehog signaling pathway for epithelial-mesenchymal transition in pancreatic cancer cells].

OBJECTIVE: To explore the blocking effects of hedgehog signaling pathway on the processes of cell migration, invasion and epithelial-mesenchymal transition (EMT) in human pancreatic cancer cells and elucidate its possible mechanisms. METHODS: The lentiviral expression vector for RNA interference of human Smoothened (SMO) gene was constructed to silence the expression of SMO. And RNAi against SMO was used to suppress the hedgehog signaling pathway in human pancreatic cancer Panc-1 cells. The in vitro invasion capacity in Panc-1 cells was assessed by Matrigel/Transwell chamber assay. Real-time PCR (polymerase chain reaction) and Western blot were used to detect the expressions of such EMT markers as E-cadherin, N-cadherin, ß-catenin, vimentin and fibronectin and such transcription factors as Snail, Slug, Twist1 and Sip1. RESULTS: The stable interference of SMO could suppress the hedgehog signaling activity in Panc-1 cells. The inhibition of hedgehog signaling reduced the in vitro invasion capacity significantly in Panc-1 cells. The expression of E-cadherin significantly increased while N-cadherin, vimentin and fibronectin were significantly down-regulated in the RNAi group. Compared to the control group, the expressions of Snail and Slug were significantly reduced in the SMO knock-down group. CONCLUSION: The inhibition of hedgehog signaling pathway reduces the in vitro invasion capacity in human pancreatic cancer cells. And the EMT process is significantly suppressed. The mechanism is partially correlated with the down-regulations of Snail and Slug.

Safety and effectiveness of inguinal hernia repair in patients with liver cirrhosis: a retrospective study and literature review.

PURPOSE: Inguinal hernia is a common feature of decompensated liver cirrhosis and a frequent cause of life-threatening complications. The traditional treatment of inguinal hernia in patients with liver cirrhosis includes non-operative management; however, emerging data suggest elective surgical repair as a preferable approach. Therefore, we aimed to assess the outcomes of inguinal hernia repair in patients with liver cirrhosis and describe their clinical characteristics. METHODS: In this retrospective study, we included a total of 28 consecutive patients with liver cirrhosis who underwent inguinal hernia repair between March 2000 and May 2019 at the First People's Hospital of Xiaoshan, Hangzhou, China. We also reviewed the literature on inguinal hernia repair in patients with liver cirrhosis. RESULTS: Emergency surgery for complicated hernia was performed in 17.9% of the study patients. Two patients developed major complications including wound hematoma in 1, who required reoperation, and gastrointestinal tract hemorrhage in the other patient, who required blood transfusion. Further, minor complications developed in 6 patients, including wound seroma in 1 and scrotal swelling in 5. Emergency hernia repair was found to be associated with a higher complication rate than elective surgery in patients with liver cirrhosis. CONCLUSION: Elective surgery for inguinal hernia repair in patients with liver cirrhosis appears to be successful and might be associated with a lower complication rate than emergency surgery. Inguinal hernia repair is recommended for patients with liver cirrhosis to prevent the development of life-threatening complications.

An acellular tissue matrix-based drug carriers with dual chemo-agents for colon cancer growth suppression.

BACKGROUND/AIMS: Relapse, metastasis, and chemo-resistance are the main factors responsible for the failure of surgical treatment of malignant tumors, and typically are the main obstacles to effective cancer treatment. Although significant advances have been made in the field of cancer chemotherapy, many patients still receive inadequate treatment due to the severe adverse effects of these drugs, resulting in an inability to reach therapeutic concentrations at the tumor site with systemic chemotherapy. Thus, a biological patch loaded with chemotherapeutic drugs could be an ideal strategy for the treatment of cancer at the tumor site. METHODS: We developed an acellular matrix using the submucosa of porcine jejunum, then loaded this matrix with different amounts of 5-fluorouracil (5-FU) and rapamycin nanoparticles. Cell proliferation and apoptosis were analyzed by flow cytometry and related markers were evaluated using real-time PCR and western blotting. The patches were evaluated in vitro to characterize their release kinetics and therapeutic feasibility. We then analyzed the therapeutic efficacy and systemic toxicity of these patches in vivo by using them in a mouse model of colon cancer. RESULTS: The patches delivered 5-FU and rapamycin in a controlled manner for more than 8 weeks, arrested the cell cycle of LoVo cells and sw480 cells at G2/M phase, and induced apoptosis in vitro. The patches also suppressed the growth of xenografted tumors in vivo with lower adverse effects than typically observed with systemic administration of these drugs. CONCLUSION: We demonstrated that patches loaded with 5-FU-RAPA-PLA-NP significantly inhibited the growth of colon cancer in vitro and in vivo. These results demonstrated the feasibility of the use of a multi-effect biological patch for cancer treatment.

Contribution of heparin to recovery of incarcerated intestine in a rat incarcerated hernia model.

PURPOSE: Inguinal hernias are the most common type of abdominal wall hernias. Although surgery is the only effective treatment for these hernias in adults, several problems associated with surgical treatment have been reported. If the hernia exits from a weak point of the abdominal wall, it can obstruct the bowel, thereby causing serious complications, including intestinal obstruction or strangulation. Through this study, we aimed to analyze the optimal incarceration induction time taken to cause some degree of necrosis from which recovery would be possible in a rat incarcerated abdominal wall hernia model and to determine the efficacy of heparin for expedite recovery from intestinal incarceration. METHODS: A rat incarcerated abdominal wall hernia model was constructed, intestinal activity and the incarceration induction time were determined based on the color of the intestine and HE staining of intestinal sections. Heparin and procaine were sprayed onto intestinal surfaces, and their effects on the recovery from intestinal incarceration were evaluated. RESULTS: Recovery from intestinal incarceration would be better if the incarceration induction time was maintained below 2.5 h in our rat model, and heparin was found to be superior to procaine in the expedite recovery from intestinal incarceration, particularly immediately after relieving such intestines. CONCLUSIONS: The results of this study are significant for planning the treatment of incarcerated inguinal hernia. Further, heparin is superior to procaine in terms of expedite recovery from intestinal incarceration.

Hedgehog signaling pathway regulates human pancreatic cancer cell proliferation and metastasis.

Pancreatic cancer is one of the most aggressive and devastating malignancies. The Hedgehog (Hh) pathway has been reported to play an important role in pancreatic cancer development and progression. The aim of this study was to examine the activation of the Hh pathway in human pancreatic cancer tissue samples and pancreatic cancer cell lines, and the molecular mechanisms involved in the Hh pathway mediated effects on pancreatic cancer cell proliferation and invasion. The expression levels of Hh molecules in human pancreatic cancer tissue samples and pancreatic cancer cell lines were evaluated using RT-PCR. The role of the Hh pathway in cell proliferation and invasion was evaluated using flow cytometry, MTT, colony formation assays and transwell invasion assays, and the expression of cancer stem cell markers and epithelial-mesenchymal transition (EMT) were evaluated using flow cytometry and RT-PCR. Tumorigenicity assays were used to further investigate the role of the Hh pathway in vivo. Hh molecules were highly expressed in human pancreatic cancer tissue samples and pancreatic cancer cell lines. Inhibition of the Hh pathway notably decreased cell proliferation and induced apoptosis through inhibition of the PI3K/AKT pathway and cancer stem cells. Furthermore, inhibition of the Hh signaling pathway significantly inhibited EMT by suppressing the activation of transcription factors Snail and Slug, which are correlated with significantly reduced pancreatic cancer cell invasion, suggesting that the Hh signaling pathway is involved in early metastasis. These results indicate that activation of the Hh pathway is a common event. Inhibition of the Hh pathway may be a potential molecular target of new therapeutic strategies for pancreatic cancer.

Combined effects of EGFR and Hedgehog signaling pathway inhibition on the proliferation and apoptosis of pancreatic cancer cells.

In the present study, we established a new experimental model to investigate the effects of EGFR targeting by RNAi, and the synergistic actions between the hedgehog (Hh) and EGFR signaling pathways on the proliferation and apoptosis in pancreatic cancer cells. Three human pancreatic cancer cell lines expressing EGFR shRNA were established, and gene expression inhibition was assessed in these lines using RT-PCR and western blot analysis. The effects of EGFR RNAi and Hh inhibition on cell proliferation and apoptosis were explored in vitro and in vivo. We observed that EGFR RNAi notably inhibited cell proliferation and colony formation, induced apoptosis and markedly decreased xenograft tumor growth. Furthermore, EGFR RNAi significantly enhanced cyclopamine sensitivity both in vitro and in vivo, and a synergistic decrease of both AKT and ERK phosphorylation was observed. The present study demonstrates that combined inhibition of both EGFR and Hh signaling pathways could establish a more promising antitumor approach than inhibiting each singly, and that there is a possible synergistic effect for Hh and EGFR signaling pathways on ERK and AKT phosphorylation.