Patient-reported outcomes at three months after pancreatic surgery for benign and malignant diseases - A prospective observational study.

BACKGROUND/OBJECTIVES: Pancreatic surgery may have a long-lasting effect on patients' health status and quality of life (QoL). We aim to evaluate patient-reported outcomes (PRO) 3 months after pancreatic surgery. METHODS: Patients scheduled for pancreatic surgery were enrolled in a prospective trial at five German centers. Patients completed PRO questionnaires (EQ-5D-5L, EORTC QLQ-PAN26, patient-reported happiness, and HADS-D), we report the first follow-up 3 months after surgery as an interim analysis. Statistical testing was performed using R software. RESULTS: From 2019 to 2022 203 patients were enrolled, a three-month follow-up questionnaire was available in 135 (65.5 %). 77 (57.9 %) underwent surgery for malignant disease. Patient-reported health status (EQ-5D-5L) was impaired in 4/5 dimensions (mobility, self-care, usual activities, pain, discomfort) for patients with malignant and 3/5 dimensions (mobility, self-care, usual activities) for patients with benign disease 3 months after surgery (p < 0.05). Patients with malignant disease reported an increase in depressive symptoms, patients with benign disease had a decrease in anxiety symptoms (HADS-D; depression: 5.00 vs 6.51, p = 0.002; anxiety: 8.04 vs. 6.34, p = 0.030). Regarding pancreatic-disease-specific symptoms (EORTC-QLQ-PAN26), patients with malignant disease reported increased problems with taste, weight loss, weakness in arms and legs, dry mouth, body image and troubling side effects at three months. Patients with benign disease indicated more weakness in arms and legs, troubling side effects but less future worries at three months. CONCLUSION: Patient-reported outcomes of patients undergoing pancreatic surgery for benign vs. malignant disease show important differences. Patients with malignant tumors report more severely decreased quality of life 3 months postoperatively than patients with benign tumors.

Comparison of 3 Methods to Assess Occupational Sevoflurane Exposure in Abdominal Surgeons: A Single-Center Observational Pilot Study.

BACKGROUND: Studies demonstrated that operating room personnel are exposed to anesthetic gases such as sevoflurane (SEVO). Measuring the gas burden is essential to assess the exposure objectively. Air pollution measurements and the biological monitoring of urinary SEVO and its metabolite hexafluoroisopropanol (HFIP) are possible approaches. Calculating the mass of inhaled SEVO is an alternative, but its predictive power has not been evaluated. We investigated the SEVO burdens of abdominal surgeons and hypothesized that inhaled mass calculations would be better suited than pollution measurements in their breathing zones (25 cm around nose and mouth) to estimate urinary SEVO and HFIP concentrations. The effects of potentially influencing factors were considered. METHODS: SEVO pollution was continuously measured by photoacoustic gas monitoring. Urinary SEVO and HFIP samples, which were collected before and after surgery, were analyzed by a blinded environmental toxicologist using the headspace gas chromatography-mass spectrometry method. The mass of inhaled SEVO was calculated according to the formula mVA = cVA·(Equation is included in full-text article.)·t·ρ VA aer. (mVA: inhaled mass; cVA: volume concentration; (Equation is included in full-text article.): respiratory minute volume; t: exposure time; and ρ VA aer.: gaseous density of SEVO). A linear multilevel mixed model was used for data analysis and comparisons of the different approaches. RESULTS: Eight surgeons performed 22 pancreatic resections. Mean (standard deviation [SD]) SEVO pollution was 0.32 ppm (0.09 ppm). Urinary SEVO concentrations were below the detection limit in all samples, whereas HFIP was detectable in 82% of the preoperative samples in a mean (SD) concentration of 8.53 µg·L (15.53 µg·L; median: 2.11 µg·L, interquartile range [IQR]: 4.58 µg·L) and in all postoperative samples (25.42 µg·L [21.39 µg·L]). The mean (SD) inhaled SEVO mass was 5.67 mg (2.55 mg). The postoperative HFIP concentrations correlated linearly to the SEVO concentrations in the surgeons' breathing zones (ß = 216.89; P < .001) and to the calculated masses of inhaled SEVO (ß = 4.17; P = .018). The surgeon's body mass index (BMI), age, and the frequency of surgeries within the last 24 hours before study entry did not influence the relation between HFIP concentration and air pollution or inhaled mass, respectively. CONCLUSIONS: The biological SEVO burden, expressed as urinary HFIP concentration, can be estimated by monitoring SEVO pollution in the personnel's individual breathing zone. Urinary SEVO was not an appropriate biomarker in this setting.

Sealing with Cyanoacrylate and a Falciform Patch Cannot Prevent Postoperative Pancreatic Fistula.

BACKGROUND: This study aimed to evaluate the effect of a new combined method of covering the pancreatic anastomosis or stump with a cyanoacrylate and a falciform patch (CAFP) on the occurrence of postoperative pancreatic fistula (POPF). METHODS: Patients undergoing a pancreaticoduodenectomy (PD) or a distal pancreatectomy (DP) were recruited over a period of 12 months. The pancreaticojejunostomy in PD and the stump in DP were sealed with cyanoacrylate glue and wrapped in a falciform patch. Incidence and severity of POPF and associated postoperative complications were retrospectively compared with historical controls of 750 PD and 336 DP at the same institution and with current data from the literature. RESULTS: The new method was applied in 27 PD and 25 DP. The rate of clinically relevant POPF after PD with CAFP was 22.2% compared to 14.4% in historical patients, p = 0.26. The rate of clinically relevant POPF after DP with CAFP was 36% compared to 30% in historical patients, p = 0.65. CONCLUSION: Sealing the pancreatic anastomosis or stump with a combination of a cyanoacrylate glue and a falciform patch didn't reduce the rate of POPF after major pancreatic resections.

The Physiological Incubation Biosimulator (PIBS): An Improved Ex Vivo Experimental Setup for the Mechanical Stability of Biological Sealants in Surgical Procedures.

BACKGROUND: Tissue-bound fibrin sealants are used in a wide array of surgical procedures. The microenvironmental interaction between sealant and application site is often poorly evaluated due to a lack of suitable experimental models. METHODS: A physiological incubation biosimulator (PIBS) was developed to test biological sealants in an ex vivo setup under physiological conditions comparable to the microenvironment at application site (temperature, humidity, pressure). PIBS was validated by a study on the effectiveness of TachoSil for leak closure at pancreatic resection sites. Defined defects in a thoracic membrane of porcine origin were sealed by TachoSil. Integrity of the sealing was tested in the presence of active pancreatic fluid over 60 minutes. Heat-inactivated pancreatic fluid and electrolyte solution served as controls. The time to leakage was recorded and experimental groups were analyzed by Kaplan-Meier analysis. RESULTS: PIBS produced reliable results. TachoSil lead to a leakage rate of 96% after incubation with active pancreatic fluid (p = 34), which was significantly higher compared with heat-inactivated pancreatic fluid (p = 34, 52%) or electrolyte solution (p = 20, 19%). CONCLUSION: PIBS is an effective tool to evaluate microenvironmental effects on the adhesive strength of biomaterials. Tissue sealing effect of TachoSil is diminished in a "pancreatic" microenvironment rich with pancreatic enzymes. Our results might therefore explain the reason of the findings of randomized controlled trials recently published on this subject.

Quantitative assessment and determinants of suture-holding capacity of human pancreas.

BACKGROUND: Hard pancreas is welcome by surgeons performing resective pancreatic surgery, because it is believed to offer better suture holding capacity (SHC), thus decreasing the risk for a postoperative leak. However, neither the actual SHC of pancreatic tissue in humans nor its determinants have been studied. METHODS: We directly measured SHC for polydioxanone 5-0 suture and tissue hardness at the pancreatic isthmus in 53 human pancreata using a dynamometer and a durometer. A histologic score based on fibrosis grade, fat content, pancreatic duct size, and signs of chronic pancreatitis was calculated for every sample. We tested the hypothesis that SHC of the pancreas was proportional to tissue hardness, and evaluated the role of different possible histomorphologic determinants of SHC. RESULTS: Suture-holding capacity correlated perfectly with tissue hardness (r = 0.98; P < 0.001; 95% confidence interval, 0.96-0.99). The histologic score showed a stronger correlation with both parameters than any single histologic parameter. The SHC of transductal sutures was significantly higher than that of pure transparenchymal sutures. The SHC and hardness were significantly lower in patients who developed a clinically relevant pancreatic fistula postoperatively. CONCLUSIONS: A mixture of histomorphologic features of human pancreas determines its tissue hardness and SHC. Involvement of the main pancreatic duct in the suture line appears to increase the mechanical strength of the pancreatic anastomosis.

The impact of the anesthetic conserving device on occupational exposure to isoflurane among intensive care healthcare professionals.

BACKGROUND: Use of anesthetic conserving devices (ACD) for inhalational isoflurane sedation in Intensive Care Units (ICU) has grown in recent years, and healthcare professionals are concerned about isoflurane pollution and exposure-related health risks. Real-time measurements to determine isoflurane exposure in ICU personnel during short-term patient care procedures and ACD handling have not yet been performed. METHODS: Isoflurane concentrations in the breathing zones of ICU staff (25 cm around the nose and mouth) were measured, by photoacoustic gas monitoring, during daily practice including tracheal suctioning, oral hygiene, body care, and patient positioning. Isoflurane pollution was further determined during ACD replacement, syringe filling, and after isoflurane spillages. RESULTS: The average mean isoflurane concentration 25 cm above patients' tracheostoma was 0.3 ppm. Mean (cmean) and maximum (cmax) isoflurane exposure in personnel's breathing zones during patient care ranged from 0.4 to 1.9 ppm and 0.7 to 6.6 ppm, respectively. Isoflurane exposure during ACD replacement was cmean 0.5 to 17.4 ppm and cmax 0.8 to 114.3 ppm. Isoflurane concentrations during ACD syringe filling ranged from 2.4 to 9.1 ppm. The maximum isoflurane concentrations after spillage were dose-dependent. CONCLUSIONS: Use of ACDs and patient physical manipulation are accompanied by isoflurane pollution. Baseline concentrations did not exceed long-term exposure limits, but short-term limits were occasionally exceeded during patient care procedures and ACD handling. Spillages should be avoided, especially when air-conditioning and scavenging systems are unavailable.

The role of TGF-beta1 as a determinant of foreign body reaction to alloplastic materials in rat fibroblast cultures: comparison of different commercially available polypropylene meshes for hernia repair.

BACKGROUND: Animal experiments on hernia repair demonstrated better biocompatibility of light-weight polypropylene meshes. However, implanted medical devices trigger a variety of adverse tissue responses, such as inflammation, fibrosis, infection and thrombosis, but the mechanisms involved in such responses remain largely unknown. This study aimed to determine the effect of transforming growth factor beta1 (TGF-beta1) on host tolerance by quantification of foreign body reaction in cultured fibroblasts depending on the amount and composition of implanted material used for hernia repair. MATERIALS AND METHODS: An NRK-49F fibroblast culture was incubated in the presence of 4 commercially available meshes approved for hernia repair. A mesh-free cell suspension served as a control group, in which the influence of TGF-beta1 on fibroblasts was evaluated. Levels of TGF-beta1 in the supernatant were dynamically measured in a time interval of 6 to 96 h and cell proliferation rates were assessed colorimetrically using MTT test. RESULTS: A dose-dependent suppression of fibroblasts proliferation by TGF-beta1 was observed. All meshes suppressed the secretion of TGF-beta1 and conversely increased significantly cell proliferation in comparison to the control group (p<0.01) in the first 24 to 48 h of incubation. That effect was more pronounced in meshes partially containing absorbable material when compared to samples of pure polypropylene meshes (p<0.05) and to the control group (p<0.001). CONCLUSION: Our experiment revealed that early biological reaction of connective tissue cells towards polypropylene meshes and their variants depended much more on the composition and type of the material than on its absolute amount. The assumption that material weight reduction alone might affect the foreign body reaction of mesh implants could not be confirmed by our in vitro study.

False-Positive PET/CT After Cyanoacrylate Sealing of a Pancreaticojejunostomy.

In 2013, a 68-year-old male had a pancreaticoduodenectomy for pancreatic cancer. The pancreaticojejunostomy was sealed with cyanoacrylate (Dermabond) to prevent postoperative pancreatic fistula. Local recurrence of malignancy at the anastomosis was suspected 18 months later in PET/CT. Surgical revision was performed and anastomosis resected. However, histology showed no tumor recurrence, but strong inflammation and foreign-body reaction towards Dermabond. The sealant caused false-positive PET/CT findings, so its use in oncologic surgery should be abandoned.

In vitro comparison of three different mesh constructions.

BACKGROUND: Material amount and pore size have been recently discussed as probable important determinants of biocompatibility of mesh implants used in hernia repair. This study aimed to find out whether other constructional parameters affect the extent of early foreign body reaction in vitro. MATERIALS AND METHODS: An NRK-49F (mixed culture of normal rat kidney cells) fibroblast culture was incubated in the presence of a 'light' microporous mesh (35 g/m(2), 0.25 mm thick), a 'heavy' polypropylene knitted mesh (95 g/m(2), 0.55 mm thick) and a polypropylene/polyglactin composite mesh (35 g/m(2), 0.5 mm thick). A mesh-free cell suspension was used as a control group. Fibroblasts' proliferation, invasion and apoptosis rates were measured by commercially available quantification tests. Levels of tumour necrosis factor-alpha, transforming growth factor-beta1, interleukin (IL)-1 beta, IL-6 and IL-10 secreted by the fibroblasts in the supernatant were dynamically measured in a time kinetics of 6-96 h. RESULTS: Invasion potential as well as proliferation and apoptosis rates of fibroblasts were enhanced by all meshes. The composite mesh stimulated the cell turnover with correspondingly increased levels of IL-6 and suppressed levels of transforming growth factor-beta1 significantly more than the two pure polypropylene meshes and the control group. CONCLUSION: Early biological response of fibroblasts as a major component of foreign body reaction was most affected by the filament construction of the mesh combining polypropylene with multifilament, partially absorbable polyglactin fibres. Material reduction did not weaken foreign body reaction. Confirming previous findings from animal experiments and clinical observations, the described in vitro model seems to be an appropriate primary tool for studying the biological tolerance towards meshes.

Improving outcomes in hernia repair by the use of light meshes--a comparison of different implant constructions based on a critical appraisal of the literature.

BACKGROUND: Despite convincing advantages offered by meshes, their use in hernia surgery remains controversial because of fears concerning the long-term effects of their implantation. To improve biocompatibility, a large variety of newly developed light meshes has been introduced to the market. This overview of the literature aimed to establish whether absolute material reduction (g per implanted mesh), use of absorbable components, and coating by inert materials are evidence-based ways to improve biocompatibility of meshes. METHOD: A review of the current English and German language literature on the outcome of groin und incisional hernia mesh repair was performed. Both basic research and clinical trials were used as sources of data. Meta-analyses and randomized controlled trials were given priority and were referred to whenever possible. RESULTS: Operative technique was an independent prognostic factor for the clinical outcome. Mesh construction and composition as characterized by pore size and filament structure appeared to be more important determinants of foreign body reaction after implantation than absolute material reduction of 1 g or more per implant. No data exist about an oncogenic effect of alloplastic materials in humans, but disturbed fertility in animal studies remains an issue of concern and should be further investigated. CONCLUSIONS: According to data from current randomized controlled trials and retrospective studies, light meshes seem to have some advantages with respect to postoperative pain and foreign body sensation. However, their use is associated with increased recurrence rates. Light meshes offer no advantages with respect to alleviating severe chronic groin pain. At the same time, experimental data reveal that material composition and mesh structure may significantly affect foreign body reaction.

Experimental comparison of monofile light and heavy polypropylene meshes: less weight does not mean less biological response.

BACKGROUND: Mesh implantation is a standard procedure in hernia repair. It provides low recurrence rate but increases complication rate due to foreign-body reaction induced by alloplastic materials in surrounding tissues. It is believed that biocompatibility of meshes may be improved by reducing their weight per meter squared (m2) and altering the implant structure. AIM: The aim of this study was to evaluate the effect of weight and structure as determinants of mesh biocompatibility. METHOD: Thirty-six Wistar rats were studied. In 12 animals, conventional polypropylene (heavy) meshes (HM) were implanted; in other 12, material-reduced (light) microporous polypropylene meshes (LM); and the remaining 12 served as a sham-operated control group. Meshes were explanted after 21 and 90 days (6 animals per group). All samples were examined by light and electron microscopies. Integration of meshes in surrounding tissue, inflammatory response, fibrotic reactions, and structural changes were recorded. Quantification of the inflammatory response was achieved by CD-68 marking of macrophages and counting their number per surface unit. RESULTS: After 21 days, there was no significant difference in thickness of surrounding connective tissue between meshes in all groups studied. After 90 days, thickness of connective tissue decreased in both groups, and fibrotic reaction in the mesh bed was significantly less in the HM group. Total amount of macrophages per millimeter squared (mm2) decreased with time in HM and LM samples but was significantly lower in the HM group on day 21 (43.5%) and day 90 (46.7%). CONCLUSION: This study found worse biocompatibility of LM compared with HM. Thus, the amount of implanted mesh was not the main determinant of biocompatibility (expressed as successful incorporation and diminished foreign-body reaction) but the size of the pores.