Lymph but Not Blood Vessel Invasion Is Independent Prognostic in Lung Cancer Patients Treated by VATS-Lobectomy and Might Represent a Future Upstaging Factor for Early Stages.

Lung cancer is the most frequent cause of cancer-related death worldwide. The patient's outcome depends on tumor size, lymph node involvement and metastatic spread at the time of diagnosis. The prognostic value of lymph and blood vessel invasion, however, is still insufficiently investigated. We retrospectively examined the invasion of lymph vessels and blood vessels separately as two possible prognostic factors in 160 patients who underwent a video-assisted thoracoscopic lobectomy for non-small-cell lung cancer at our institution between 2014 and 2019. Lymph vessel invasion was significantly associated with the UICC stage, lymph node involvement, tumor dedifferentiation, blood vessel invasion and recurrence. Blood vessel invasion tended to be negative prognostic, but missed the level of significance (p = 0.108). Lymph vessel invasion, on the other hand, proved to be a prognostic factor for both histological subtypes, adenocarcinoma (p < 0.001) as well as squamous cell carcinoma (p = 0.018). After multivariate analysis apart from the UICC stage, only lymph vessel invasion remained independently prognostic (p = 0.018). Remarkably, we found analogue survival curve progressions of patients with stage I, with lymph vessel invasion, compared to stage II non-small-cell lung cancer. After further validation in prospective studies, lymph vessel invasion might be considered as an upstaging factor in resectable lung cancer. Especially in the early-stage of the disease, it might represent an additional risk factor to consider adjuvant therapy after surgical resection.

New Diabetic Medication Sodium-Glucose Cotransporter-2 Inhibitors Can Induce Euglycemic Ketoacidosis and Mimic Surgical Diseases: A Case Report and Review of Literature.

Background: Euglycemic diabetic ketoacidosis (EDKA) is a potentially life-threatening condition and a reported side effect of antidiabetic sodium-glucose-cotransporter-2-inhibitors (SGLT2-I). The analysis of the herein presented case and its management formed the incentive to prepare this multidisciplinary work and includes an overview about perioperative SGLT2-I-induced ketoacidosis. Method: A PubMed search on relevant entries was conducted combining the terms "euglycemic diabetic ketoacidosis" AND "surgery." Results: A total of 33 articles on SGLT2-I-induced ketoacidosis in the context of surgical treatment were identified. According to this literature research risk factors for the development are infection, perioperative fasting, surgical stress, and insulin dose reduction. Conclusion: Unspecific symptoms mimicking acute abdomen and normoglycemia can lead to delayed diagnosis of EDKA and might harm patients under SGLT2-I therapy in the perioperative setting. SGLT2-I medication should be withheld for at least 24-48 h prior to surgery according to this review of literature and restarted only in stable clinical conditions to avoid the severe complication of EDKA.

Small and Laterally Placed Incisional Hernias Can be Safely Managed with an Onlay Repair.

INTRODUCTION: In meta-analyses and systematic reviews, clear advantages have been identified for the sublay versus onlay technique for treatment of incisional hernias. Nonetheless, an expert panel has noted that the onlay mesh location may be useful in certain settings. MATERIALS AND METHODS: First, unadjusted analysis of data from the Herniamed Registry was performed to compare 6797 sublay operations with 1024 onlay operations for repair of incisional hernias. Then, using propensity score matching to account for the influence of variables age, gender, ASA score, BMI, risk factors, preoperative pain, defect size, and defect localization, 1016 pairs were formed and compared with each other. RESULTS: Unadjusted analysis revealed that the onlay operation was used significantly more often for small defects, lateral defect localization, and in women. After comparing the propensity score-matched pairs, no significant difference was found between the sublay and onlay technique in the outcome criteria intra- and postoperative complications, general complications, complication-related reoperations, pain at rest, pain on exertion, chronic pain requiring treatment, and recurrence on 1-year follow-up. But that was true only for this carefully selected patient collective. CONCLUSION: In a selected patient collective with small and lateral incisional hernias and with a large proportion of women, outcomes obtained for the onlay and sublay techniques do not differ significantly.

Delayed closure of open abdomen in septic patients treated with negative pressure wound therapy and dynamic fascial suture: the long-term follow-up study.

INTRODUCTION: Negative pressure wound therapy (NPWT) is widely used in the treatment of open abdomen (OA). The use of dynamic fascial sutures (DFS) increases the rate of successful delayed closure by reducing fascial lateralization. We recently published a prospective controlled trial including 87 patients undergoing abdominal surgery for secondary peritonitis between 2007 and 2012. Patients were treated with NPWT and DFS for approximation of fascial edges. The present study represents a follow-up assessment of these patients 5-9 years after OA treatment with NPWT and DFS. METHODS: The 39 patients still alive were included in the recent study according to the protocol of our last study in 2013. All patients received a questionnaire regarding long-term complications after OA treatment between 2007 and 2012. Mean follow-up was 5-9 years. Analyzed parameters included pain, the presence of incisional hernia, and subsequent surgical interventions. Results were analyzed quantitatively. RESULTS: One patient had deceased since the last publication in 2013, and hence 38 patients were included in the current study. The median age was 60.9 (25.2-86.1) years, and 17 (44.7%) were females. Overall 56.3% of the original 87 patients had died during the long-term follow-up period. 21 patients (55.3%) answered the questionnaire. Six (28.6%) declared that they suffered from pain in the previous operating field, five (23.8%) at rest, and three (14.3%) during exercise. In five patients (23.8%), pain lasted for more than 3 months. One patient (4.8%) still requires analgesic treatment. Among the 21 patients, seven (33.3%) were found to have incisional hernias. Three hernias (42.9%) were treated by surgery. CONCLUSION: Incisional hernia rates after OA treatment remain high, but are accompanied by little pain. The ideal technique of fascial closure after NPWT should be investigated in further research.

Emerging Trends in Abdominal Wall Reinforcement: Bringing Bio-Functionality to Meshes.

Abdominal wall hernia is a recurrent issue world-wide and requires the implantation of over 1 million meshes per year. Because permanent meshes such as polypropylene and polyester are not free of complications after implantation, many mesh modifications and new functionalities have been investigated over the last decade. Indeed, mesh optimization is the focus of intense development and the biomaterials utilized are now envisioned as being bioactive substrates that trigger various physiological processes in order to prevent complications and to promote tissue integration. In this context, it is of paramount interest to review the most relevant bio-functionalities being brought to new meshes and to open new avenues for the innovative development of the next generation of meshes with enhanced properties for functional abdominal wall hernia repair.

Assessment of Pain and Quality of Life in Lichtenstein Hernia Repair Using a New Monofilament PTFE Mesh: Comparison of Suture vs. Fibrin-Sealant Mesh Fixation.

BACKGROUND: Inguinal hernia repair is one of the most common operations in general surgery. The Lichtenstein tension-free operation has become the gold standard in open inguinal hernia repair. Despite the low recurrence rates, pain and discomfort remain a problem for a large number of patients. The aim of this study was to compare suture fixation vs. fibrin sealing by using a new monofilament PTFE mesh, i.e., the Infinit(®) mesh by W. L. Gore & Associates. METHODS: This study was designed as a controlled prospective single-center two-cohort study. A total of 38 patients were enrolled and operated in Lichtenstein technique either standard suture mesh fixation or fibrin-sealant mesh fixation were used as described in the TIMELI trial. Primary outcome parameters were postoperative complications with the new mesh (i.e., seroma, infection), pain, and quality of life evaluated by the VAS and the SF-36 questionnaire. Secondary outcome was recurrence assessed by ultrasound and physical examination. Follow-up time was 1 year. RESULTS: Significantly, less postoperative pain was reported in the fibrin-sealant group compared to the suture group at 6 weeks (P = 0.035), 6 months (P = 0.023), and 1 year (P = 0.011) postoperatively. Additionally, trends toward a higher postoperative quality of life, a faster surgical procedure, and a shorter hospital stay were seen in the fibrin-sealant group. CONCLUSION: Fibrin-sealant mesh fixation in Lichtenstein hernioplasty effectively reduces acute and chronic postoperative pain. Monofilament, macro-porous, knitted PTFE meshes seem to be a practicable alternative to commonly used polypropylene meshes in open inguinal hernia repair.

Delayed closure of open abdomen in septic patients is facilitated by combined negative pressure wound therapy and dynamic fascial suture.

INTRODUCTION: The aim of this prospective controlled trial was the definition of the optimal timepoint for delayed closure after negative pressure wound therapy (NPWT) in the treatment of the open abdomen (OA) in septic patients after abdominal surgery. The delayed closure of the abdominal wall after abdominal NPWT treatment is often problematic due to the lateralization of the fascial edge leading to unfavorably high tensile forces of the adapting sutures in the midline. We present the results of an innovative combination of NPWT with a new fascial-approximation technique using dynamic fascial sutures (DFS) and delayed closure of the abdominal wall. METHODS: Eighty-seven patients subjected to OA therapy following surgery for secondary peritonitis were treated with NPWT and DFS. In all patients, a running suture of elastic vessel loops was used to approximate fascial edges. This procedure was continued for the duration of NPWT until final closure of the abdomen with running suture in 55 patients (63.2 %) and interrupted suture technique in eight patients (9.2 %). An anterior component separation was performed in seven patients. RESULTS: Delayed closure was achieved in 68 patients (78.2 %) after 12.6 days [mean (SD) 25.1 (2-204)] days and 4.3 re-operations [mean (SD) 6.0 (1-43)]. Fifteen (17.2 %) superficial and two (2.3 %) deep wound infections occurred. In three (3.4 %) cases, entero-atmospheric fistulas had to be treated. We recorded no technique-specific complications. Four (5.9 %) incisional hernia were detected in a mean follow-up of 40.5 months (16-65). Mortality rate was 55.2 %. CONCLUSION: Using a new technique combining NPWT and DFS in the treatment of the OA, the delayed closure of the fascial edges by running suture can be achieved and the number of re-operations can be kept low. The technique was safe and led to a low incidence of incisional hernias. Extensive abdominal wall reconstruction was seldom required.

Transporous hernia mesh fixation with fibrin sealant in an in vitro model of spray application.

BACKGROUND: The spray application of fibrin sealant (FS) is widely used for atraumatic mesh fixation in open and laparoscopic hernia surgery. Studies focusing on the optimization of sealant distribution are rare. This study elucidates the impact of spray distance and pressure, the thrombin concentration of the FS, as well as the mesh design on the spray process and the resulting sealant distribution. Furthermore, the effect of interrupting the spray process on sealant distribution was investigated. MATERIAL AND METHODS: Three different meshes were sprayed in a vertical test arrangement with 0.4 mL FS. Fibrin sealants containing 4 and 500 IU/mL thrombin (Tisseel and Artiss; Vienna, Austria) provided by Baxter Biosciences were used. The application distances varied from 5 to 8 cm. The relative fibrin sealant distribution on the individual mesh surfaces was evaluated and compared, as well as loss of FS and patterns of clot formation. RESULTS: Spray distances between 5 and 8 cm led to a homogenous sealant distribution. Lower thrombin concentrations led to significant losses of FS due to slower polymerization. Differences of the fibrin sealant distribution and mesh pore sizes were found. No differences between continuous and discontinuous application were observed. CONCLUSION: The spray application of FS provides a uniform sealant film in a defined range of distances. However, design and pore size of different meshes substantially impact sealant distribution. These findings should be considered when selecting prosthesis for hernia repair. In general, the amount of sealant should not exceed 0.08 mL per cm(2) to avoid obstruction of mesh pores.

Use of fibrin sealant (Tisseel/Tissucol) in hernia repair: a systematic review.

BACKGROUND: Abdominal wall and inguinal hernia repair are the most frequently performed surgical procedures in the United States and Europe. However, traditional methods of mesh fixation are associated with a number of problems including substantial risks of recurrence and of postoperative and chronic pain. The aim of this systematic review is to summarize the clinical safety and efficacy of Tisseel/Tissucol fibrin sealant for hernia mesh fixation. METHODS: A PubMed title/abstract search was conducted using the following terms: (fibrin glue OR fibrin sealant OR Tisseel OR Tissucol) AND hernia repair. The bibliographies of the publications identified in the search were reviewed for additional references. RESULTS: There were 36 Tisseel/Tissucol studies included in this review involving 5,993 patients undergoing surgery for hernia. In open repair of inguinal hernias, Tisseel compared favorably with traditional methods of mesh fixation, being associated with shorter operative times and hospital stays and a lower incidence of chronic pain. Similarly, after laparoscopic/endoscopic inguinal hernia repair, Tisseel/Tissucol was associated with less use of postoperative analgesics and less acute and chronic postoperative pain than tissue-penetrating mesh-fixation methods. Other end points of concern to surgeons and patients are the risks of inguinal hernia recurrence and of complications such as hematoma formation and intraoperative bleeding. Comparative studies show that Tisseel/Tissucol does not increase the risk of these outcomes and may, in fact, decrease the risk compared with tissue-penetrating fixation methods. When used in the repair of incisional hernias, Tisseel/Tissucol significantly decreased both postoperative morbidity and duration of hospital stay. CONCLUSIONS: Clinical evidence published to date supports the use of Tisseel/Tissucol as an option for mesh fixation in open and laparoscopic/endoscopic repair of inguinal and incisional hernias. Guidelines of the International Endohernia Society recommend fibrin sealant mesh fixation, especially in inguinal hernia repair. Nonfixation is reserved for selected cases.

A comparative biomechanical evaluation of hernia mesh fixation by fibrin sealant.

BACKGROUND: The atraumatic fixation of meshes by fibrin sealant (FS) has been established for both open and laparoscopic techniques of hernia repair. This study was performed to evaluate the use of FS in hernia mesh fixation with different polymerization speed (thrombin concentrations), using commercial hernia meshes, and in two techniques, transabdominal preperitoneal mesh placement (TAPP) and intraperitoneal mesh placement (IPOM). MATERIALS AND METHODS: A median laparotomy was performed in a pig model and hernia meshes were placed in IPOM and TAPP techniques. After mesh fixation with FS using thrombin concentrations of 4 and 500 IU/mL, maximum shear force before failure was measured at 5, 60, and 120 min. RESULTS: At both thrombin concentrations and in all meshes in which the technique was used, the TAPP method tended to show higher maximum force levels at failure than did the IPOM method. In both TAPP and IPOM techniques and in all meshes, the 4 IU/mL thrombin concentration FS was superior to the 500 IU/mL thrombin concentration sealant. CONCLUSIONS: Although both thrombin concentrations are suitable for mesh fixation, lower concentrations allow slower polymerization and better sealant diffusion leading to higher maximum force levels at failure. The TAPP method was biomechanically superior to the IPOM method. There were no major differences between mesh products.

The feasibility of FS mesh fixation by a transgastric approach--an important benefit in future NOTES procedures?

BACKGROUND: Preserving the integrity of the abdominal wall is a major benefit in NOTES procedures. It may result in a decrease of postoperative (postOP) pain, infection, and port site hernia. This experimental study on intra-peritoneal onlay mesh (IPOM) repair was designed to apply meshes by a transgastric access (TGA) and to use a combination of transfascial sutures and fibrin sealant as fixation. MATERIALS AND METHODS: Four abdominal wall defects were created by TGA under laparoscopic control in five nonsurvival and three survival pigs (4, 11, and 22 d observation period). Titanized polypropylene meshes were fixed transfascially by four polypropylene sutures using a "suture passer" device. Meshes were additionally fixed with 0.2 mL of fibrin sealant (FS) by an endoscopic application. TGA was closed with endoclips in the nonsurvival model and with laparoscopic suturing in survival pigs. RESULTS: The three survival pigs were euthanized on the d 4, 11, and 22 postOP. The macroscopic evaluation revealed excellent integration of the meshes without signs of shrinkage, dislocation, or inflammation. Histology confirmed macroscopic findings. CONCLUSIONS: Our findings confirm that IPOM repair of ventral hernia in an experimental NOTES hybrid procedure is feasible. This study also demonstrates the technical feasibility and the potential advantages of FS mesh fixation to further reduce trauma to the abdominal wall following the key principles of the NOTES approach.

A comparison of a cyanoacrylate [corrected] glue (Glubran) vs. fibrin sealant (Tisseel) in experimental models of partial pulmonary resection and lung incision [corrected] in rabbits.

INTRODUCTION: Bronchopleural fistulas (BPF) and air leaks (AL) present major complications after pulmonary resection. Various tissue sealants have been proposed for their prevention, e.g., fibrin sealant (FS) and cyanoacrylate glues (CA). Contrary to the safety record of FS, substantial side effects such as foreign body reaction and impaired tissue integration have been reported for CA. This study compares the sealing efficacy and biocompatibility as well as side effects of FS and CA in experimental partial pulmonary resection and lung incision in rabbits. METHODS: 26 New Zealand white rabbits (3 kg) were randomized to one of the three groups: partial pulmonary resection (A, acute model; n = 7 FS/ 7CA), lung incision [2 (B; n = 3 FS/ 3 CA)], and 14-day observation period (C; n = 3 FS/ 3 CA). In all groups (A, B, and C), FS was considered as control and CA as treatment. Surgery was carried out in general anaesthesia and mechanical ventilation. For partial lung resection a median thoracotomy was performed and the apex of the left median lobe was resected and the parenchymal surface covered with 0.09 ml of FS and CA. The thoracic cavity was filled with ringer solution after 5 minutes. The inspiratory minute volume (IMV) was increased by 0.02 l after every 4th inspiration. In groups B and C, a left lateral thoracotomy was performed in the 4th intercostal space and the left median lobe was incised with a scalpel. The incision was covered with 0.5 ml of FS or CA. At autopsy (B and C) the operation site was assessed macroscopically. Histology was performed in all animals. RESULTS: In terms of sealing purposes, FS and CA yielded comparable results in all groups. CA elicited a substantial increase of tissue temperature in the acute phase immediately after application (A). After 14 days CA residues were found, whereas FS was completely degraded. Histology showed a pronounced inflammatory response to CA but not to FS. We conclude that although the effect of airtight sealing was equally satisfying, our results emphasize that FS is preferable to CA for the prevention of BPF and AL due to superior biocompatibility and degradability. Longterm effects of CA residues on pulmonary tissue require further experimental testing.

Small intestine submucosa (SIS) implants in experimental IPOM repair.

BACKGROUND: Synthetic meshes can cause adverse effects (e.g., adhesions, mesh infection) in intraperitoneal onlay mesh repair (IPOM). Although data for its biocompatibility as well as degradation behavior is still scarce, small intestine submucosa (SIS) implants have been suggested as a favorable alternative for IPOM repair. The aim of the study was to assess safety and efficacy of SIS used as allo- or xenograft in an experimental model of IPOM repair, with the purpose of creating a critical awareness for specific aspects of the biomesh concept among researchers and surgeons alike. Main outcome parameters were adhesion formation, tissue integration, shrinkage, and dislocation. MATERIALS AND METHODS: Open IPOM repair was performed in 16 Sprague Dawley rats and two minipigs. SIS implants were 2 x 2 cm in rats (one per animal) and 6 x 8 cm in pigs (four per animal). All implants were fixed with six nonresorbable sutures. Observation period was 17 and 28 d (n =8) in rats and 28 d in pigs. Outcome parameters were assessed macroscopically, and histologic samples (H and E staining) were obtained. RESULTS: Upon autopsy, SIS appeared to be only moderately integrated. Dislocation of five SIS implants in the rats and of two SIS implants in the pigs were observed although all sutures were still in place. No seroma formation or infection was detected macroscopically, but substantial shrinkage and adhesion formation at the margins of implants and suture sites were frequently observed. Histology confirmed the macroscopic finding of limited integration and substantial shrinkage. The pathomorphology was similar in both species. CONCLUSIONS: Small intestine submucosa implants are susceptible to shrinkage, dislocation, and adhesion formation in experimental IPOM repair in rats and pigs. These findings are in accordance with literature and warrant further investigations of SIS implants in hernia repair.

Fibrin sealant (Tisseel) for hiatal mesh fixation in an experimental model in pigs.

BACKGROUND: This study was designed to assess the efficacy of the fibrin sealant fixation of titanized polypropylene mesh in experimental hiatal mesh closure in pigs. Prosthetic hiatal closure is recommended for the repair of large hiatal/paraesophageal hernias as well as for antireflux surgery. However, only limited data exist on the favorable choice of meshes and fixation devices. Migration of the implant and trauma to neighboring organs due to perforating devices, such as sutures or tacks, present potentially lethal complications. In this study, we propose the fixation of titanized polypropylene meshes (TS) specifically developed for hiatal closure (TISure; GfE Medizintechnik GmbH, Nuremberg, Germany) with human fibrin sealant (FS, Tisseel; Baxter Biosciences, Vienna, Austria). MATERIALS AND METHODS: A laparotomy was carried out in 7 mini-pigs (27-30 kg bodyweight) under general anaesthesia, and a TS was implanted after precise dissection of the right and left crura and the crural commissure. The key hole of the TS was placed around the esophagus at the gastroesophageal junction. One mL of FS was applied with the Easy Spray system (Baxter Biosciences, Vienna, Austria) for circular and three dimensional mesh fixation onto the diaphragm. Due to the lack of accepted gold standards of hiatal mesh reinforcement, no control group was used. Animals were sacrificed after 4 wk, and meshes were explanted after macroscopical assessment of the correct position and tissue integration. Histology was performed. RESULTS: All meshes showed excellent tissue integration and no signs of migration or dislocation. FS was completely degraded and replaced by well vascularized fibroblastic tissue. CONCLUSIONS: Titanized polypropylene mesh with FS fixation was found to be a safe and efficient combination for reinforcement of the hiatal closure in this preliminary experimental model.