Chronic postsurgical pain (CPSP): an underestimated problem after incisional hernia treatment.

BACKGROUND: Chronic postsurgical pain (CPSP) is a potential long-term problem following open incisional hernia repair which may affect the quality of life of patients despite successful anatomical repair of the hernia. The aim of this manuscript was to identify the incidence and outcome of patients following open incisional hernia repair in respect of risk factors to develop CPSP. METHODS: A single-center retrospective analysis of patients who underwent open incisional hernia repair between 2015 and 2021 was performed. Pre-existing conditions (e.g., diabetes mellitus and malignancy), hernia complexity, postoperative complications, and postoperative pain medication were analyzed using the local database. Quality of life and CPSP were assessed using the EuraHS Quality of Life (QoL) questionnaire. RESULTS: A total of 182 cases were retrospectively included in a detailed analysis based on the complete EuraHS (QoL) questionnaire. During the average follow-up period of 46 months, this long-term follow-up revealed a 54.4% incidence of CPSP and including a rate of 14.8% for severe CPSP (sCPSP) after open incisional hernia surgery. The complexity of the hernia and the demographic variables were not different between the group with and without CPSP. Patients with CPSP reported significantly reduced QoL. The analgesics score which includes the need of pain medication in the initial days after surgery was significantly higher in patients with CPSP than in those without (no CPSP: 2.86 vs. CPSP: 3.35; p = 0.047). CONCLUSION: The presence of CPSP after open incisional hernia repair represents a frequent and underestimated long-term problem which has been not been recognized to this extent before. CPSP impairs QoL in these patients. Patients at risk to develop CPSP can be identified in the perioperative setting by the need of high doses of pain medication using the analgesics score. Possibly timely adjustment of pain medication, even in the domestic setting, could alleviate the chronicity or severity of CPSP.

Postoperative Analgesics Score as a Predictor of Chronic Postoperative Inguinal Pain After Inguinal Hernia Repair: Lessons Learned From a Retrospective Analysis.

BACKGROUND: Chronic postoperative inguinal pain (CPIP) is a common complication after inguinal hernia surgery and occurs in up to 10-14% of cases. CPIP has a significant impact on daily life, work ability and thus compromises quality of life. The aim of this retrospective study was an in-depth analysis of patients undergoing inguinal hernia repair to further refine the prediction of the onset of CPIP reliably. METHODS: A single center retrospective analysis of patients with who underwent open or minimally invasive inguinal hernia repair from 2016 to 2021 was carried out. Complication rates, detailed analysis of postoperative pain medication and quality of life using the EuraHS Quality of Life questionnaire were assessed. RESULTS: Out of 596 consecutive procedures, 344 patients were included in detailed analyses. While patient cohorts were different in terms of age and co-morbidities, and the prevalence of CPIP was 12.2% without differences between the surgical procedures (Lichtenstein: 12.8%; TEP 10.9%; TAPP 13.5%). Postoperative pain was evaluated using a newly developed analgesic score. Patients who developed CPIP later had a significant higher consumption of analgesics at discharge (p = 0.016). As additional risk factors for CPIP younger patient age and postoperative complications were identified. CONCLUSION: The prospective use of the analgesic score established here could be helpful to identify patients that are at risk to develop CPIP. These patients could benefit from a structured follow-up to allow early therapeutic intervention to prevent chronification and restore the quality of life.

[Preoperative iron deficiency with/without anemia-an underestimated risk factor?] / Präoperativer Eisenmangel mit/ohne Anämie ­ ein unterschätzter Risikofaktor?

BACKGROUND: Every third surgical patient already suffers from anemia before surgery. The main cause is iron deficiency. OBJECTIVE: This article describes the perioperative risk of iron deficiency with/without anemia and summarizes potential preventive measures. MATERIAL AND METHODS: Presentation of various current original papers, guidelines and own experiences from the German patient blood management network. RESULTS AND CONCLUSION: Preoperative iron deficiency with/without anemia is an underestimated risk factor for perioperative complications. The implementation of preoperative diagnostics and treatment as part of a comprehensive patient blood management reduces complications and increases patient safety.

Bladder Augmentation Using Lyoplant®: First Experimental Results in Rats.

Background: Congenital defects of the urinary bladder (micro- or contracted bladder, bladder exstrophy) remain a challenging problem for pediatric surgeons. Even when conservative treatment options are fully exhausted, irreversible renal dysfunction can be observed in a large number of cases that can even lead to chronic renal failure and the need for kidney transplantation. To protect kidney function bladder augmentation using intestinal tissue is commonly applied as the standard treatment method. However due to the unphysiological nature of intestinal tissue a number of problems and complications such as urinary tract infections or bladder stone formation limit the clinical success of this approach. Moreover a number of substitutes for the implementation of a bladder augmentation have been tested without success to date. Here we used an experimental model to test wether the biocompatible collagen mesh Lyoplant may be a suitable candidate for bladder augmentation. Methods: We implanted a biocompatible collagen mesh (Lyoplant®) in a bladder defect rat model for bladder augmentation (Lyoplant®-group: n = 12; sham group n = 4). After 6 weeks the abdomen was reopened and the initial implant as well as the bladder were resected for histological and immunohistochemical examination. Results: All but one rat exhibited physiological growth and behaviour after the operation without differences between the Lyoplant®-group (n = 12) and the sham group (n = 3). One rat from the sham group had to be excluded because of a suture leakage. No wound healing complications, wound infections and no herniation were observed. After 5 weeks the implants showed an adequate incorporation in all cases. This was confirmed by immunohistological analyses where a significant cell infiltration and neovascularization was observed. Conclusion: In summary, Lyoplant® appears to be a promising tool in experimental bladder augmentation/regeneration in rats.

Slowdown in Antarctic mass loss from solid Earth and sea-level feedbacks.

Geodetic investigations of crustal motions in the Amundsen Sea sector of West Antarctica and models of ice-sheet evolution in the past 10,000 years have recently highlighted the stabilizing role of solid-Earth uplift on polar ice sheets. One critical aspect, however, that has not been assessed is the impact of short-wavelength uplift generated by the solid-Earth response to unloading over short time scales close to ice-sheet grounding lines (areas where the ice becomes afloat). Here, we present a new global simulation of Antarctic evolution at high spatiotemporal resolution that captures all solid Earth processes that affect ice sheets and show a projected negative feedback in grounding line migration of 38% for Thwaites Glacier 350 years in the future, or 26.8% reduction in corresponding sea-level contribution.

[Phosphodiesterase 4 inhibition for treatment of endothelial barrier and microcirculation disorders in sepsis]. / Phosphodiesterase-4-Inhibition zur Therapie der endothelialen Schranken- und Mikrozirkulationsstörung in der Sepsis.

Sepsis is commonly associated with loss of microvascular endothelial barrier function (capillary leak) and dysfunctional microcirculation, which both promote organ failure. The development of a distinct therapy of impaired endothelial barrier function and disturbed microcirculation is highly relevant because both of these phenomena constitute crucial processes which critically influence the prognosis of patients. Numerous in vivo and in vitro trials over the past years have fostered a better understanding of the pathophysiology of capillary leak. Furthermore, promising data in animal models show that therapeutic modulation of endothelial barrier function and microcirculation can be achieved by stabilizing endothelial cAMP (cyclic adenosine monophosphate) levels followed by activation of Rho-GTPase Rac1, e. g. by phosphodiesterase 4 inhibitors. This review summarizes and discusses recent findings of cellular mechanisms and in vivo trials.

[Updated definition of sepsis : Implications for diagnostics and therapy principles]. / Neue Definition der Sepsis : Implikationen für Diagnostik und Therapieprinzipien.

Until a short time ago the criteria for sepsis were based on the assumption that sepsis is primarily caused by the inflammatory reaction of the body to an infection, which does not correspond to the current knowledge on the pathophysiology of sepsis. Accordingly, sepsis is now defined as a life-threatening organ dysfunction due to a falsely regulated response of the body to an infection. Septic shock occurs when a condition of persisting hypotension with the continuous need for vasopressor agents and serum lactate levels of >2 mmol/l despite administration of sufficient volume and fluid is present. These new definitions are discussed in this article with respect to the consequences for the diagnosis of sepsis. This review article also presents the current controversies on the most important aspects of the therapy of sepsis.

[Late complications and functional disorders after rectal resection : Prevention, detection and therapy]. / Spätpostoperative Komplikationen und Folgezustände nach Rektumresektion : Prävention, Erkennung, Therapie.

The prognosis of patients with rectal carcinoma has been improved with the implementation of multimodal therapy and improvement of the surgical technique. Therefore, late complications and functional consequences that determine the quality of life following oncological rectal resection are increasingly being recognized. In general both the surgical trauma and side effects of the multimodal therapy play a critical role in the manifestation of various problems in the long-term course after treatment of rectal carcinoma. In this context the low anterior resection syndrome (LARS) has been described which is influenced by different factors and can be worsened by neoadjuvant radiation. Disorders of the urinary bladder and sexual dysfunction as well as benign anastomotic stenoses are problems independent of LARS. Therapeutic approaches for these late complications and functional disorders have either been insufficiently evaluated or are not available. Treatment of functional disorders can be attempted by pelvic floor training, biofeedback and sacral nerve stimulation. Interventional and surgical procedures are available to treat anastomotic stenosis. It must be emphasized that an adequate surgical technique is indispensable to avoid most of these late complications and functional disorders.

[Is a different view on the pathophysiology of sepsis the key for novel therapeutic options?]. / Sepsis: neue Erkenntnisse, andere Perspektiven - neue Therapieoptionen?

Sepsis remains a critical problem in virtually all fields of clinical medicine. Despite intensive scientific and clinical efforts no significant progress has emerged in the fight against sepsis mortality. Solely the algorithm of the "surviving sepsis campaign" has proven to result in significantly enhanced survival of sepsis patients when consequently adopted. Novel research in the field of the complex immunological alterations in sepsis suggests that ongoing immunosuppression is the critical determinant underlying sepsis mortality. Therefore, it was proposed that immunostimulation might be a successful approach to improve outcome in individually selected patients. Others favor a different view on the pathophysiology of sepsis and support the notion that the manifestation of organ failure may be the dominant therapeutic target. Due to the fact that breakdown of the microcirculation and disruption of the microvascular barrier are critical events preceding organ failure, experimental therapeutic efforts to address these events led to promising results. Taken together, in view of the many initially promising experimental data and the failure to translate them into successful clinical therapies, a different view on the pathophysiology of sepsis is warranted to obtain the key for novel therapeutic options.

Recurrence after perineal rectosigmoidectomy: when and why?

AIM: Reported recurrence rates after perineal rectosigmoidectomy (Altemeier's procedure) in patients with full-thickness rectal prolapse vary from 0% to 60%. The object of this study was to analyse risk factors for recurrence after this procedure. METHOD: From May 2004 to December 2012, 63 consecutive patients suffering from full-thickness rectal prolapse undergoing perineal rectosigmoidectomy were included. Of these 46 were female and the median age of the whole group was 79 (30-90) years. The median follow-up was 53 (3-99) months. Patient characteristics and operative parameters were compared between patients with and without recurrence. RESULTS: One patient died and another patient needed re-operation. Eight full-thickness recurrences occurred in eight patients after a median of 18 (6-48) months. Stapled compared with handsewn anastomosis (hazard ratio 7.96, 95% confidence interval 1.90-33.47; P = 0.001) and shorter specimen length (hazard ratio 4.06, 95% confidence interval 0.97-16.99; P = 0.03) increased the risk of recurrence in Cox regression analysis. CONCLUSION: The operative technique including stapled anastomosis and length of the resected specimen seems to be associated with a high recurrence rate after perineal rectosigmoidectomy.

Influence of apneic oxygenation and minimal tidal volumes on ventilator-associated lung injury.

BACKGROUND: Protective tidal volumes such as 6 mL/kg can still result in tidal hyperinflation and expose the lung to mechanical stress. Further reduction of tidal volume and apneic oxygenation might mitigate lung injury. We aimed to assess the influence of minimal tidal volumes and apneic oxygenation in combination with arterio-venous extracorporeal lung assist (av-ECLA) on ventilator-associated lung injury. METHODS: Acute respiratory distress syndrome was induced in swine (N.=24) by saline lavage. The animals were randomized into three groups, ventilated in a pressure-controlled mode with a tidal volume (VT) of 6 mL/kg, 3 mL/kg and 0 mL/kg body weight, respectively. The latter two groups were instrumented with an av-ECLA device. Lung injury was assessed by histological examination of lung tissue at the end of the 24 hour experiment and by gas exchange parameters. RESULTS: Oxygenation was significantly lower in the 3 and 0 mL/kg groups, whereas CO2 remained in the targeted range in all groups. Histological examination revealed a reduction of tidal hyperinflation in the apical lung regions in the 3 and 0 mL/kg groups. In lower lung regions an increase of inflammation, intra-alveolar exudation and formation of atelectasis was shown in the animals ventilated with lower VTs. CONCLUSION: In combination with highly effective CO2-removal, the reduction of tidal volumes up to 0 mL was feasible. Tidal hyperinflation could be reduced in the upper lung areas, yet inflammation in the lower lung was higher with low tidal volumes. This stresses the differing mechanical properties of inhomogeneous injured lungs.

The abnormal proplatelet formation in MYH9-related macrothrombocytopenia results from an increased actomyosin contractility and is rescued by myosin IIA inhibition.

BACKGROUND: Mutations in the MYH9 gene cause autosomal dominant MYH9-related diseases (MYH9-RD) that associate macrothrombocytopenia with various other clinical conditions. The mechanisms giving rise to giant platelets remain poorly understood. OBJECTIVES/PATIENTS: To study the proplatelet formation (PPF) derived from megakaryocytes (MKs) generated in vitro from 11 patients with MYH9-RD with different mutations, compared with controls. METHODS: Proplatelet formation from cultured patients' MKs was evaluated with or without blebbistatin or the ROCK inhibitor Y27632. Myosin IIA and actin distribution were studied in spreading MKs on different surfaces by immunoconfocal analysis. Kinetic studies of contractility were performed on spreading MKs and the impact of blebbistatin on the maturation of the patients' MKs was evaluated by electron microscopy. RESULTS AND CONCLUSIONS: We show that in vitro MKs of 11 patients formed significantly fewer proplatelets than controls. MKs from MYH9-RD displayed an abnormal spreading on polylysine, fibronectin and collagen, with a disorganized actin network and a marked increase in stress fiber formation. Traction force microscopy studies demonstrated an elevated level of contractile forces in adherent mutated MKs. The myosin II inhibitor blebbistatin and the ROCK inhibitor Y27632 both rescued the proplatelet formation defect and normalized the ultrastructural characteristics of MYH9-RD MKs. Altogether, our results show that in MYH9-RD, mutations modify the overall MYH9 function and provoke a proplatelet defect through an excess of actomyosin contractility in spreading MKs. These results may promote new therapeutic strategies aimed at reducing this actomyosin contractility.

Lessons and challenges during a 5-year follow-up of 21 Composix Kugel implantations.

INTRODUCTION: From its introduction in 2000 until its US recall in December 2005, the Composix Kugel mesh was implanted in an estimated 350,000 patients worldwide. In our patients, minor postoperative complications were followed after a few years by more serious problems (persistent abdominal pain, infections, intestinal perforations). In this study, we take stock after a 5-year follow-up and issue a plea for improved product development strategies and the creation of hernia registries. PATIENTS AND METHODS: Between 2003 and 2006, we implanted the Bard(®) Composix(®) Kugel(®) mesh in 21 patients (11 men, 10 women, mean age 63.2 ± 13.7 years) with incisional hernias using the open intraperitoneal onlay mesh technique. The mesh is made on one side of ePTFE and on the other of polypropylene and is expanded by a polyethylene (PET) memory recoil ring. The average follow-up was 45.5 months. All patients had at least one risk factor for hernia recurrence. Explanted prostheses were analyzed by scanning electron microscopy (SEM) and subjected to mechanical strength tests. RESULTS: During the postoperative course, six patients suffered a wound healing disorder. Ten patients complained of persistent abdominal wall pain and four experienced recurrence of the hernia. In one patient, the mesh had to be explanted due to chronic infection. In one patient, the PET memory recoil ring broke after 5 years of follow-up with consequent small bowel perforation. The PET memory recoil ring exhibited clear signs of degradation on SEM and unmistakable signs of material fatigue in a materials testing machine. CONCLUSIONS: Patients with recalled Composix Kugel meshes face a singular risk for complications that may occur even many years after implantation. The most serious complication is the breakage of its PET memory recoil ring. Since the recall of the Composix Kugel Mesh, we have discontinued its use. It is necessary that future complications are documented in a common post-market surveillance registry. Algorithms need to be developed and promoted to support affected patients and surgeons.

Perineal rectosigmoidectomy: quality of life.

AIM: For any surgical treatment of full-thickness rectal prolapse, little attention has been given to quality of life (QoL). This study prospectively evaluated continence, constipation and QoL after perineal rectosigmoidectomy for full-thickness rectal prolapse in young and elderly patients in the long term. METHOD: From May 2003 to May 2010, consecutive patients suffering from full-thickness rectal prolapse and treated with perineal rectosigmoidectomy were prospectively studied. A standardized questionnaire, including the Cleveland Clinic Constipation Score (CCCS), the Cleveland Clinic Incontinence Score (CCIS) and generic [EuroQol five-dimension (EQ-5D)] and constipation-specific [Patient Assessment of Constipation-Quality of Life (PAC-QOL)] QoL scores, was administered pre- and postoperatively. The Wilcoxon test (for EQ-5D data) and two-sample Student's t-test [for EuroQol visual analogue scale (EQ-VAS), CCCS, CCIS and PAC-QOL data) were used for statistical analyses. RESULTS: Fifty-three patients (47 women), 72.7 (range 30-89) years of age, underwent perineal rectosigmoidectomy. One patient died and one patient needed reoperation. Five full-thickness recurrences occurred. Thirty-seven patients completed the follow-up questionnaire at a median of 49 (range, 6-89) months. Postoperative incontinence and constipation improved significantly (CCIS from 13 ± 7.28 to 8.7 ± 6.96 and CCCS from 8.32 ± 6.96 to 3.49 ± 4.17). Furthermore, QoL, in terms of mobility, usual activity, pain/discomfort and anxiety/depression and subjective state of health, were significantly better at follow-up (P < 0.001). All dimensions of constipation-related QoL improved (P < 0.001). The results did not differ significantly between patients under or over 69 years of age. CONCLUSION: Patients' experience improved general and constipation-related QoL after perineal rectosigmoidectomy, and this was independent of age.

Glucocorticoid-induced tumour necrosis factor receptor expression: a potential molecular link between steroid intake and complicated diverticulitis?

AIM: Immunosuppression and steroid medication have been identified as risk factors for complicated sigmoid diverticulitis. The underlying molecular mechanisms have not yet been elucidated. We hypothesized that glucocorticoid-induced tumour necrosis factor receptor (GITR) and matrix metalloproteinase-9 (MMP-9) might play a role. METHOD: GITR and MMP-9 were analysed at protein [immunohistochemistry/immunofluorescence (IF)] and messenger RNA level (real-time polymerase chain reaction) in surgical specimens with complicated and non-complicated diverticulitis (n=101). IF double staining and regression analysis were performed for both markers. GITR expression was correlated with clinical data and its usefulness as a diagnostic test was investigated. RESULTS: High GITR expression (≥41%) was observed in the inflammatory infiltrate in complicated diverticulitis, in contrast to non-complicated diverticulitis where GITR expression was low (P<0.001). High GITR expression was significantly associated with steroid use and pulmonary diseases (both P<0.001). MMP-9 expression correlated with GITR expression (R(2) =0.7268, P<0.0001, r=0.85) as demonstrated with IF double-staining experiments. Co-labelling of GITR with CD68, but not CD15, suggested that GITR-expressing cells in diverticulitis are macrophages. GITR expression was superior to C-reactive protein (CRP), white cell count and temperature in distinguishing complicated and non-complicated diverticulitis. CONCLUSIONS: Our results suggest that GITR expression in inflammatory cells might potentially indicate a molecular link between steroid use and complicated forms of acute sigmoid diverticulitis. Increased MMP-9 expression by GITR signalling might explain the morphological changes in the colonic wall of perforated and phlegmonous diverticulitis. Analysis of soluble GITR might be a promising strategy for future research.

Predictive factors for postoperative constipation and continence after stapled transanal rectal resection.

BACKGROUND: Although stapled transanal rectal resection (STARR) has become an important surgical option in the treatment of obstructive defaecation syndrome, objective data about parameters that predict its success or failure are not yet available. METHODS: Medical history, clinical and radiomorphological data were obtained prospectively from a multi-institutional STARR registry. Predictive factors for postoperative constipation (Cleveland Clinic Constipation Score, CCS) and incontinence (Cleveland Clinic Incontinence Score, CCIS) were identified using univariable and multivariable analysis. RESULTS: Data were obtained for 181 of 201 patients in the STARR registry, with completed median follow-up of 19·4 (range 12-41) months. Although the CCS decreased significantly overall (from mean(s.d.) 16·3(4·9) to 6·7(4·1); P < 0·001), 31 patients (17·1 per cent) complained about persisting constipation. CCIS levels remained unchanged overall, but 16 patients (8·8 per cent) had new-onset faecal incontinence. Multivariable analysis revealed that rectocele (ß = -0·302, P < 0·001) and intussusception (ß = -0·392, P < 0·001) were independent predictors of low CCS levels, and intussusception (ß = -0·216, P = 0·001) and enterocele (ß = -0·171, P = 0·012) were independent predictors of low CCIS levels. In contrast, small rectal diameter (ß = -0·293, P < 0·001), low squeeze pressure (ß = -0·188, P = 0·005) and increased pelvic floor descent at rest (ß = 0·264, P < 0·001) predicted high CCIS levels. CONCLUSION: Factors for a favourable outcome after STARR included rectocele, intussusception and enterocele, whereas small rectal diameter, low sphincter pressure and increased pelvic floor descent were unfavourable. These findings should be integrated into the therapy algorithm for STARR.

[MYH9 syndrome and auto-immune haemolytic anaemia: an unrelated association?]. / Syndrome MYH9 et anémie hémolytique auto-immune : une association fortuite?

INTRODUCTION: The MYH9 syndrome is a group of rare autosomal dominant platelet disorders associating in most of the cases a macrothrombocytopenia and characteristic leukocyte inclusions. Clinical features may include renal, visual, or hearing impairment. The bleeding tendency is usually moderate. CASE REPORT: We report a 28-year-old-man, with an auto-immune haemolytic anaemia associated with a MYH9 syndrome. CONCLUSION: To our knowledge, this is the first report of such an association.

Diagnostic and therapeutic considerations on inherited platelet disorders in neonates and children.

Inherited disorders of platelets constitute a group of rare diseases that give rise to bleeding syndromes of variety severity, with more severe cases being first diagnosed during infancy and childhood. To appropriate diagnose a platelet function disorder during early childhood the knowledge of the physiological characteristics of platelets in the paediatric population is mandatory. Apart from thrombocytopenia which is quite common in neonates and children the present overview is aimed to focus on inherited platelet function disorders. Furthermore, knowledge on platelet maturation and reference values according to age are given, and a diagnostic strategy specifically adapted to a pediatric population is presented on the bases of plasmatic and molecular laboratory methodologies. Finally, therapeutic approaches are briefly summarized (antifibrinolytic agents, Desmopressin, HLA-matched platelets, recombinant factor VIIa).

Multiplate whole blood impedance point of care aggregometry: preliminary reference values in healthy infants, children and adolescents.

BACKGROUND: The aim of the present study was to evaluate paediatric reference values for platelet function using a point-of-care whole blood impedance aggregometry. METHODS, RESULTS & CONCLUSION: In 265 healthy infants and children aged