The p-rpS6-zone delineates wounding responses and the healing process.

The spatial boundaries of tissue response to wounding are unknown. Here, we show that in mammals, the ribosomal protein S6 (rpS6) is phosphorylated in response to skin injury, forming a zone of activation surrounding the region of the initial insult. This p-rpS6-zone forms within minutes after wounding and is present until healing is complete. The zone is a robust marker of healing as it encapsulates features of the healing process, including proliferation, growth, cellular senescence, and angiogenesis. A mouse model that is unable to phosphorylate rpS6 shows an initial acceleration of wound closure, but results in impaired healing, identifying p-rpS6 as a modulator but not a driver of healing. Finally, the p-rpS6-zone accurately reports on the status of dermal vasculature and the effectiveness of healing, visually dividing an otherwise homogeneous tissue into regions with distinct properties.

The Rate of Avoidable Pancreatic Resections at a High-Volume Center: An Internal Quality Control and Critical Review.

BACKGROUND: The incidence of benign diseases among pancreatic resections for suspected malignancy still represents a relevant issue in the surgical practice. This study aims to identify the preoperative pitfalls that led to unnecessary surgeries at a single Austrian center over a twenty-year period. METHODS: Patients undergoing surgery for suspected pancreatic/periampullary malignancy between 2000 and 2019 at the Linz Elisabethinen Hospital were included. The rate of "mismatches" between clinical suspicion and histology was considered as primary outcome. All cases that, despite that, fulfilled the indication criteria for surgery were defined as minor mismatches (MIN-M). Conversely, the true avoidable surgeries were identified as major mismatches (MAJ-M). RESULTS: Among the 320 included patients, 13 (4%) presented with benign lesions at definitive pathology. The rate of MAJ-M was 2.8% (n = 9), and the most frequent causes of misdiagnoses were autoimmune pancreatitis (n = 4) and intrapancreatic accessory spleen (n = 2). In all MAJ-M cases, various mistakes within the preoperative workup were detected: lack of multidisciplinary discussion (n = 7, 77.8%); inappropriate imaging (n = 4, 44.4%); lack of specific blood markers (n = 7, 77.8%). The morbidity and mortality rates for mismatches were 46.7% and 0. CONCLUSION: All avoidable surgeries were the result of an incomplete pre-operative workup. The adequate identification of the underlying pitfalls could lead to minimize and, potentially, overcome this phenomenon with a concrete optimization of the surgical-care process.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Long-Term Quality of Life after Pancreatic Surgery for Intraductal Papillary Mucinous Neoplasm.

INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMNs) represent the most common precancerous cystic lesions of the pancreas. The aim of our study was to investigate if resection for non-invasive IPMNs alters quality of life (QoL) in a long-term follow-up. METHODS: Patients (n = 50) included in the analysis were diagnosed and resected from 2010 to 2016. QoL was assessed at a median of 5.5 years after resection. At that point in time, the current QoL as well as the QoL before resection was evaluated retrospectively. The standardised European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Pancreatic Cancer (EORTC QLQ - PAN26) was applied for the QoL assessment. RESULTS: After a median of 66 months postoperatively, the total QoL score significantly worsened (92.13 vs. 88.04, p = 0.020, maximum achievable score = 100) for patients (median age at surgery 68.0 years), mostly due to digestive symptoms. During the same follow-up period, median Eastern Cooperative Oncology Group (ECOG) performance status did not worsen (p = 0.003). CONCLUSIONS: Long-term QoL statistically significantly worsened after pancreatic resection for IPMN. The extent of worsening, however, was small, and QoL still remained excellent. Therefore, resection in cases of IPMN is appropriate, if indicated carefully.

Total resection of a giant retroperitoneal and mediastinal ganglioneuroma-case report and systematic review of the literature.

BACKGROUND: Ganglioneuromas (GNs) are extremely rare, slowly growing, benign tumors that can arise from Schwann cells, ganglion cells, and neuronal or fibrous tissues. Due to their origin from the sympathetic neural crest, they show neuroendocrine potential; however, most are reported to be hormonally inactive. Nevertheless, complete surgical removal is recommended for symptom control or for the prevention of potential malignant degeneration. CASE REPORT: A 30-year-old female was referred to our oncologic center due to a giant retroperitoneal and mediastinal mass detected in computed tomography (CT) scans. The initial symptoms were transient nausea, diarrhea, and crampy abdominal pain. There was a positive family history including 5 first- and second-degree relatives. Presurgical biopsy revealed a benign ganglioneuroma. Total resection (TR) of a 35 × 25 × 25 cm, 2550-g tumor was obtained successfully via laparotomy combined with thoracotomy and partial incision of the diaphragm. Histopathological analysis confirmed the diagnosis. Surgically challenging aspects were the bilateral tumor invasion from the retroperitoneum into the mediastinum through the aortic hiatus with the need of a bilateral 2-cavity procedure, as well as the tumor-related displacement of the abdominal aorta, the mesenteric vessels, and the inferior vena cava. Due to their anatomic course through the tumor mass, the lumbar aortic vessels needed to be partially resected. Postoperative functioning was excellent without any sign of neurologic deficit. CONCLUSION: Here, we present the largest case of a TR of a GN with retroperitoneal and mediastinal expansion. On review of the literature, this is the largest reported GN resected and was performed safely. Additionally, we present the first systematic literature review for large GN (> 10 cm) as well as for resected tumors growing from the abdominal cavity into the thoracic cavity.

A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms: An International Multicenter Cohort Study.

Background: Oncological survival after resection of pancreatic neuroendocrine neoplasms (panNEN) is highly variable depending on various factors. Risk stratification with preoperatively available parameters could guide decision-making in multidisciplinary treatment concepts. C-reactive Protein (CRP) is linked to inferior survival in several malignancies. This study assesses CRP within a novel risk score predicting histology and outcome after surgery for sporadic non-functional panNENs. Methods: A retrospective multicenter study with national exploration and international validation. CRP and other factors associated with overall survival (OS) were evaluated by multivariable cox-regression to create a clinical risk score (CRS). Predictive values regarding OS, disease-specific survival (DSS), and recurrence-free survival (RFS) were assessed by time-dependent receiver-operating characteristics. Results: Overall, 364 patients were included. Median CRP was significantly higher in patients >60 years, G3, and large tumors. In multivariable analysis, CRP was the strongest preoperative factor for OS in both cohorts. In the combined cohort, CRP (cut-off ≥0.2mg/dL; hazard-ratio (HR):3.87), metastases (HR:2.80), and primary tumor size ≥3.0cm (HR:1.83) showed a significant association with OS. A CRS incorporating these variables was associated with postoperative histological grading, T category, nodal positivity, and 90-day morbidity/mortality. Time-dependent area-under-the-curve at 60 months for OS, DSS, and RFS was 69%, 77%, and 67%, respectively (all p < 0.001), and the inclusion of grading further improved the predictive potential (75%, 84%, and 78%, respectively). Conclusions: CRP is a significant marker of unfavorable oncological characteristics in panNENs. The proposed internationally validated CRS predicts histological features and patient survival.

Outcome in Patients Treated With Cytoreductive Surgery and HIPEC for Gastric Cancer With Peritoneal Carcinomatosis.

BACKGROUND/AIM: We compared patients with advanced gastric cancer [Union for International Cancer Control (UICC) III] versus patients with stage UICC IV and peritoneal carcinomatosis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) versus patients with stage UICC IV treated without HIPEC to ascertain if CRS and HIPEC improve overall survival (OS). PATIENTS AND METHODS: We retrospectively analysed thirty-seven advanced gastric cancer patients who had been treated at our department from 2012 to 2017. The endpoint was median OS. RESULTS: Eighteen (49%) patients with UICC stage III showed a median OS of 37.4 months. Eight (21%) patients in the HIPEC group reached a median OS of 33.8 months. Median OS in the UICC IV group (11 patients, 30%) treated with a palliative concept was 6.2 months and therefore significantly worse (p=0.004). CONCLUSION: A systemic approach combined with CRS and HIPEC in selected stage IV gastric cancer patients improves the OS comparable to patients in UICC stage III.

Evolution of Transluminal Necrosectomy for Acute Pancreatitis to Stent in Stent Therapy: Step-Up Approach Leads to Low Mortality and Morbidity Rates in 302 Consecutive Cases of Acute Pancreatitis.

Background: The step-up approach, using either flexible endoscopy or a minimal invasive retroperitoneal access, has reduced mortality and morbidity in patients with acute pancreatitis. The use of fully covered self-expanding metal stents (FCSEMS) or lumen apposing metal stents (LAMS) facilitates endoscopic necrosectomy and drainage of walled-off necrosis (WON). The aim of our analysis was to investigate the 30/90/365-day mortality and morbidity rates of the subtypes of the revised Atlanta classification for acute pancreatitis. Materials and Methods: We conducted a retrospective analysis of all patients (n = 302) treated with acute pancreatitis in our institution from January 2014 to July 2017. Mortality, morbidity, management of fluid collections, interventions, complications, and new onset of diabetes were recorded. Results: In 30.8% (n = 93/302) of patients, pancreatic fluid collection developed. Out of these, 58.1% (54/93) required intervention, consisting of endoscopic treatment in 63% (34/54) or multidisciplinary approach in 37% (20/54). Overall, 90-day mortality rate according to Kaplan-Meier Estimator was 3.7%. Overall, 1-year mortality rate was 6.2%. One-year mortality for uncomplicated acute pancreatic fluid collection, pseudocyst, and WON were 5.4%, 2.6%, and 13.5%, respectively. Hemorrhage in case of metal stent treatment (FCSEMS/LAMS) occurred in 14.3%. If LAMS was combined with double pigtail stent-in-stent, bleeding was seen in 5.3%. No transperitoneal necrosectomy was needed. Conclusions: Treating acute pancreatitis with a step-up approach, including stent-in-stent procedures, leads to low mortality rates and few stent-associated bleeding complications and minimizes necessity for open transperitoneal surgical necrosectomy.

Exploring the surgical landscape of pancreatic neuroendocrine neoplasia in Austria: Results from the ASSO pNEN study group.

INTRODUCTION: Pancreatic neuroendocrine neoplasia (pNEN) show increasing incidence and management is complex due to biological heterogeneity. Most publications report isolated high-volume single-centre data. This Austrian multi-centre study on surgical management of pNENs provides a comprehensive real-life picture of quality indicators, recurrence-patterns, survival factors and systemic treatments. METHODS: Retrospective, national cohort-study from 7 medium-/high-volume centres in Austria, coordinated under the auspices of the Austrian Society of Surgical Oncology (ASSO). RESULTS: Two-hundred patients underwent resection for pNEN, 177 had non-functioning tumours and 31 showed stage 4 disease. Participating centres were responsible for 2/3 of pNEN resections in Austria within the last years. The mean rate of completeness of variables was 98.6%. Ninety-days mortality was 3.5%, overall rate of complications was 42.5%. Morbidity did not influence long-term survival. The 5-year overall-survival (OS) was 81.3%, 10-year-OS 52.5% and 5-year recurrence-free-survival (RFS) 69.8%. Recurrence was most common in the liver (68.1%). Four out of five patients with recurrence underwent further treatment, most commonly with medical therapy or chemotherapy. Multivariable analysis revealed grading (HR:2.7) and metastasis (HR:2.5) as significant factors for relapse. Tumours-size ≥2 cm (HR:5.9), age ≥60 years (HR:3.1), metastasis (HR:2.3) and grading (HR:2.0) were associated with OS. Tumours <2 cm showed 93.9% 10-year-OS, but 33% had G2/G3 grading, 12.5% positive lymph-nodes and 4.7% metastasis at diagnosis, each associated with significant worse survival. CONCLUSION: Resection of pNENs in Austria is performed with internationally comparable safety. Analysed factors allow for risk-stratification in clinical treatment and future prospective trials. A watch-and-wait strategy purely based on tumour-size cannot be recommended.

Minimal Invasive Linea Alba Reconstruction for the Treatment of Umbilical and Epigastric Hernias with Coexisting Rectus Abdominis Diastasis.

INTRODUCTION: Patients with umbilical or epigastric hernias benefit from mesh- based repairs, and even more so if a concomitant rectus diastasis (RD) is present. The ideal technique is, however, still under debate. In this study we introduce the minimal invasive linea alba reconstruction (MILAR) with the supraaponeurotic placement of a fully absorbable synthetic mesh. MATERIALS AND METHODS: Midline reconstruction with anterior rectus sheath repair and mesh augmentation by an open approach is a well-known surgical technique for ventral hernia repair. Between December 1, 2016, and November 30, 2017, 20 patients with symptomatic umbilical and/or epigastric hernias, and coexisting RD underwent a minimally invasive complete reconstruction of the midline through a small access route. The inner part of both incised and medialized anterior rectus sheaths was replaced by a fully absorbable synthetic mesh placed in a supraaponeurotic position. RESULTS: Patients were hospitalized for an average of 4 days and the mean operating time was 79 minutes. The mean hernia defect size was 1.5 cm in diameter and the mean mesh size was recorded as 15.8 cm in length and 5.2 cm in width. Two patients sustained surgical postoperative complications in terms of symptomatic seroma occurrences with successful interventional treatment.The early results (mean follow-up period of 5 months) showed no recurrences and only 1 patient reported occasional pain following exertion without rest. DISCUSSION: MILAR is a modification of the recently published endoscopic linea alba reconstruction restoring the normal anatomy of the abdominal wall. A new linea alba is formed with augmentation of autologous tissue consisting of the plicated anterior rectus sheaths. Supraaponeurotic placement of a fully absorbable synthetic mesh eliminates potential long-term mesh-associated complications. Regarding MILAR, there is no need for endoscopic equipment due to the uniquely designed flexible lighted retractors, meaning one assistant less is required.

A Novel Technique for Parastomal Hernia Repair Combining a Laparoscopic and Ostomy-Opening Approach.

INTRODUCTION: The aim of this study was to evaluate a new method of parastomal hernia (PSH) repair by using a hybrid approach with a cylindrical-shaped mesh of 4 cm funnel length. MATERIALS AND METHODS: In a pilot prospective case series, 12 patients underwent surgical repair of PSHs with a combined laparoscopic and ostomy-opening approach. After laparoscopic adhesiolysis, the ostomy opening was excised from outside and the bowel was closed. The hernia sac was excised after reduction of its content. Then, the bowel was guided through the funnel of the mesh and the implant was manually transferred into the peritoneal cavity through the hernia defect. Next, the fascial margins were narrowed with sutures. Laparoscopy was continued, and the mesh was placed and fixed with absorbable tacks in the proper position. Finally, the diverted bowel was shortened outside of the abdomen and the stoma was matured in its original location. RESULTS: We documented no mesh-associated complications. Only one superficial peristomal wound defect occurred. No unplanned conversions were needed, and median duration of the operations was 72 minutes. There was no recurrence during the short-term follow-up of median 4 months (ranged from 3 to 8 months). DISCUSSION: The technique described gives several advantages, such as a minimally invasive hybrid approach creating a real three-dimensional mesh-covered barrier between the trephine and stomal limb and optional shortening of a concomitant prolapse. When needed due to a concomitant incisional hernia, a second flat mesh can be laparoscopically placed in an intraperitoneal position.

Evolution of Endoscopic Anterior Component Separation to a Precostal Access with a New Cylindrical Balloon Trocar.

INTRODUCTION: Endoscopic anterior component separation (ECS) techniques facilitate tension-free midline closure of wide ventral hernia defects. We describe a novel approach with a precostal incision and a new cylindrical ballon trocar. MATERIALS AND METHODS: A single-center analysis of 19 patients undergoing ECS between January 1, 2014 and August 2, 2017 was performed with regard to improvement of technique. We currently start with a lateral precostal incision. This access in a low-fat and stable area allows for easy identification of the external oblique muscle with the ribs functioning as dorsal abutment for entering the correct plane between external and internal oblique muscles. Then a trocar is inserted with a cylindrical ballon, thus providing sufficient pneumatic widening of the dissection plane. A second 5-mm port is inserted under direct vision below the 12th rib. From there a unidirectional incision of the external oblique aponeurosis is performed from subcostal to the inguinal ligament. If necessary, the cephalad muscular parts of the external oblique can be transected over several centimeters in both directions starting from the precostal incision. RESULTS: We documented no procedure-related complications apart from two hematomas that required no interventions. Four procedures were carried out on one side and the remaining ones bilaterally. In one case, a conversion to conventional open component separation was required due to extensive scarring after open cholecystectomy. There were no notable abdominal bulgings or lateral hernias during a structured postoperative follow-up period of 1 year postoperatively. DISCUSSION: The technique described offers advantages in terms of determination of the correct entry point for ECS, regardless of abdominal wall conditions and the precostal access allows for unidirectional dissection toward the inguinal ligament with only two trocars in total. The cylindrical shape of the ballon trocar provides adequate widening of the working space and ensures good overview for safe dissection.

Parastomal Hernia Repair with a 3D Funnel Intraperitoneal Mesh Device and Same-Sided Stoma Relocation: Results of 56 Cases.

BACKGROUND: Parastomal hernias (PSHs) are a common and challenging issue. In previous studies, three-dimensional (3D) funnel mesh devices have been used successfully for the repair of PSHs. METHODS: We performed an analysis of prospectively collected data of patients who underwent a same-sided stoma reposition with 3D funnel-shaped mesh augmentation in intraperitoneal (IPOM) position at our department between the years of 2012 and 2015. Primary outcome parameters were intra- and postoperative surgical complications and recurrence rate during the follow-up period. RESULTS: Fifty-six patients could be included in this analysis. PSH repair was performed in 89.3% as elective surgery and in 73% in laparoscopic technique. A concomitant incisional hernia (EHS type 2 and 4) was found in 50% and repaired in a single-step procedure with PSH. Major postoperative complications requiring redo surgery (Clavien-Dindo ≥3b) were identified in 8.9% (5/56). Overall recurrence rate was 12.5% (7/56). Median follow-up time was 38 months, and a 1-year follow-up rate of 96.4% was reached. CONCLUSION: PSH repair with 3D funnel mesh in IPOM technique is safe, efficient and easy to perform in laparoscopic and open surgical approaches providing advantageous results compared to other techniques. Furthermore, simultaneous detection and treatment of concomitant incisional hernias has shown favorable. However, the mesh funnel distends and becomes shortened encasing a bulky bowel mesentery and further shrinkage happens eccentric. Changing mesh construction according to lengthening the funnel could possibly lead to reduction in recurrence.

Fast Early Recovery After Transabdominal Preperitoneal Repair in Athletes with Sportsman's Groin: A Prospective Clinical Cohort Study.

BACKGROUND: Current literature on chronic groin pain suggests that laparoscopic mesh repair on athletes enables a faster recovery and subsequent return to unrestricted athletic activities. The aim of this study was to evaluate the role of transabdominal preperitoneal (TAPP) mesh repair in athletes resistant to conservative therapy. METHODS: A multidisciplinary approach with tailored physiotherapy. Thirty-nine professional athletes with chronic groin pain were referred to surgery at a single clinic. A full assessment was carried out on each, including medical history, physical examination, dynamic ultrasound, and pelvic magnetic resonance imaging. TAPP repair was performed using a polypropylene mesh and fibrin glue fixation on 30 athletes who had exhibited typical symptoms, shown resistance to conservative therapy, not benefited from accompanying physiotherapy, and had ceased training in the 3 to 6 months prior. The outcome measures were early postoperative recovery of 6 weeks and full resumption of athletic activities. RESULTS: Mean duration of symptoms from onset to surgical repair was 7 months. Conservative treatment had improved symptoms temporarily or to some extent in 7 athletes, while 2 ceased competing altogether. Twenty-three athletes exhibited unilateral and 16 bilateral groin pain. Laparoscopy confirmed posterior wall deficiency in 24 and true inguinal hernia in 6 athletes. Mild scrotal hematoma occurred in 2 athletes postoperatively; all were discharged within 24 hours of surgery. Twenty-one (70%) returned to sports activities after 6 weeks of convalescence. Persistent mild pain was experienced by 5 athletes postoperatively for up to 1 year, yet did not interfere with normal daily activity. Twenty-five participants (85%) reported full satisfaction with the procedure 1 year after treatment; all returned to the same or even higher level of athletic performance. CONCLUSION: The study confirms that the endoscopic placement of retropubic mesh is an efficient, safe, and minimally invasive treatment that enables fast early recovery.