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Millions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks. Here, we present a holistic solution in the form of a modular, intelligent suture support sealant patch capable of containing and detecting leaks early. The pH and/or enzyme-responsive triggerable sensing elements can be read out by point-of-need ultrasound imaging. We demonstrate reliable detection of the breaching of sutures, in as little as 3 hours in intestinal leak scenarios and 15 minutes in gastric leak conditions. This technology paves the way for next-generation suture support materials that seal and offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables. Digestive surgical leaks manifesting days after a successful surgery can lead to severe complications and affect healthcare worldwide. Here, the authors address the problem holistically with a hydrogel patch capable of sealing tissues, while detecting imminent leaks via a smartphone-operated ultrasound probe.

ATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously suggested putative prognostic markers ABCC2 and SLC22A3 in pancreatic cancer patients. Protein localization and brush border staining intensity of ABCC2 and SLC22A3 was assessed in tumor tissue blocks of 65 pancreatic cancer patients and associated with clinical data and survival of patients with regard to therapy. Negative SLC22A3 brush border staining in pancreatic tumors significantly increased the risk of both disease progression and patient´s death in univariate analyses. Multivariate analyses confirmed the association of SLC22A3 expression with progression-free survival of patients. A subgroup analysis of patients treated with regimens based on nucleoside analogs suggested that patients with negative brush border staining or apical localization of SLC22A3 in tumor cells have worse overall survival. The combination of positive ABCC2 and negative SLC22A3 brush border staining predicted worst overall survival and patients with positive brush border staining of both proteins had best overall and progression-free survival. The present study shows for the first time that the protein presence and to some extent also localization of SLC22A3 significantly associate with prognosis of pancreatic cancer in both unstratified and chemotherapy-treated patients. The combination of ABCC2 and SLC22A3 brush border staining also needs further attention in this regard.

To evaluate a novel anticoagulation strategy in an extracorporeal circuit, we introduce a device that induces local hypothermia as blood flows through the circuit. Using a pig model, we assessed its technical feasibility, biocompatibility, and safety. Sixteen pigs were randomly assigned to either the cooled group or the control group and underwent midline laparotomy to establish extracorporeal circulation (blood flow 500 ml/min) via the caudal vena cava for up to four hours. Blood samples were collected at baseline and at 15, 60, and 240 min during the experiment. In the cooled group, blood was cooled to 20 °C and then rewarmed to 37 °C, while in the control group, blood was maintained at 37 °C. A total of 6 cooled and 4 control pigs completed 4 h of the experiment. Our findings confirm the technical feasibility of the proposed device, which effectively maintained the required temperature differentials while keeping the pressure differentials in the circuit within 150 mmHg. No issues with circuit patency were observed. Additionally, no adverse effects were detected on erythrocyte stability. Within the limitation of the short observation period, no adverse effects were observed on renal, liver, or cardiac function. Our data suggest that local hypothermia in the extracorporeal circuit may mitigate surgery-induced inflammation.

Telomeric sequences, the structures comprised of hexanucleotide repeats and associated proteins, play a pivotal role in chromosome end protection and preservation of genomic stability. Herein we address telomere length (TL) dynamics in primary colorectal cancer (CRC) tumour tissues and corresponding liver metastases. TL was measured by multiplex monochrome real-time qPCR in paired samples of primary tumours and liver metastases along with non-cancerous reference tissues obtained from 51 patients diagnosed with metastatic CRC. Telomere shortening was observed in the majority of primary tumour tissues compared to non-cancerous mucosa (84.1%, p < 0.0001). Tumours located within the proximal colon had shorter TL than those in the rectum (p < 0.05). TL in liver metastases was not significantly different from that in primary tumours (p = 0.41). TL in metastatic tissue was shorter in the patients diagnosed with metachronous liver metastases than in those diagnosed with synchronous liver metastases (p = 0.03). The metastatic liver lesions size correlated with the TL in metastases (p < 0.05). Following the neoadjuvant treatment, the patients with rectal cancer had shortened telomeres in tumour tissue than prior to the therapy (p = 0.01). Patients with a TL ratio between tumour tissue and the adjacent non-cancerous mucosa of ≥ 0.387 were associated with increased overall survival (p = 0.01). This study provides insights into TL dynamics during progression of the disease. The results show TL differences in metastatic lesions and may help in clinical practice to predict the patient’s prognosis.

There is a lack of systematic research exploring cross-species variation in liver lobular geometry and zonation patterns of critical drug-metabolizing enzymes, a knowledge gap essential for translational studies. This study investigated the critical interplay between lobular geometry and key cytochrome P450 (CYP) zonation in four species: mouse, rat, pig, and human. We developed an automated pipeline based on whole slide images (WSI) of hematoxylin-eosin-stained liver sections and immunohistochemistry. This pipeline allows accurate quantification of both lobular geometry and zonation patterns of essential CYP proteins. Our analysis of CYP zonal expression shows that all CYP enzymes (besides CYP2D6 with panlobular expression) were observed in the pericentral region in all species, but with distinct differences. Comparison of normalized gradient intensity shows a high similarity between mice and humans, followed by rats. Specifically, CYP1A2 was expressed throughout the pericentral region in mice and humans, whereas it was restricted to a narrow pericentral rim in rats and showed a panlobular pattern in pigs. Similarly, CYP3A4 is present in the pericentral region, but its extent varies considerably in rats and appears panlobular in pigs. CYP2D6 zonal expression consistently shows a panlobular pattern in all species, although the intensity varies. CYP2E1 zonal expression covered the entire pericentral region with extension into the midzone in all four species, suggesting its potential for further cross-species analysis. Analysis of lobular geometry revealed an increase in lobular size with increasing species size, whereas lobular compactness was similar. Based on our results, zonated CYP expression in mice is most similar to humans. Therefore, mice appear to be the most appropriate species for drug metabolism studies unless larger species are required for other purposes, e.g., surgical reasons. CYP selection should be based on species, with CYP2E1 and CYP2D6 being the most preferable to compare four species. CYP1A2 could be considered as an additional CYP for rodent versus human comparisons, and CYP3A4 for mouse/human comparisons. In conclusion, our image analysis pipeline together with suggestions for species and CYP selection can serve to improve future cross-species and translational drug metabolism studies.

Anastomotic leakage is a severe complication in gastrointestinal surgery. It is often a reason for reoperation together with intestinal passage blockage due to formation of peritoneal adhesions. Different materials as local prevention of these complications have been studied, none of which are nowadays routinely used in clinical practice. Nanofabrics created proved to promote healing with their structure similar to extracellular matrix. We decided to study their impact on anastomotic healing and formation of peritoneal adhesions. We performed an experiment on 24 piglets. We constructed 3 hand sutured end-to-end anastomoses on the small intestine of each pig. We covered the anastomoses with a sheet of polycaprolactone nanomaterial in the first experimental group, with a sheet of copolymer of polylactic acid with polycaprolactone in the second one and no fortifying material was used in the Control group. The animals were sacrificed after 3 weeks of observation. Clinical, biochemical and macroscopic signs of anastomotic leakage or intestinal obstruction were monitored, the quality of the scar tissue was assessed histologically, and a newly developed scoring system was employed to evaluate the presence of adhesions. The material is easy to manipulate with. There was no mortality or major morbidity in our groups. No statistical difference was found inbetween the groups in the matter of level of peritoneal adhesions or the quality of the anastomoses. We created a new adhesion scoring system. The material appears to be safe however needs to be studied further to prove itsʹ positive effects.

Anastomotic leakage (AL) is the leaking of non‐sterile gastrointestinal contents into a patient's abdominal cavity. AL is one of the most dreaded complications following gastrointestinal surgery, with mortality rates reaching up to 27%. The current diagnostic methods for anastomotic leaks are limited in sensitivity and specificity. Since the timing of detection directly impacts patient outcomes, developing new, fast, and simple methods for early leak detection is crucial. Here, a naked eye‐readable, electronic‐free macromolecular network drain fluid sensor is introduced for continuous monitoring and early detection of AL at the patient's bedside. The sensor array comprises three different macromolecular network sensing elements, each tailored for selectivity toward the three major digestive enzymes found in the drainage fluid during a developing AL. Upon digestion of the macromolecular network structure by the respective digestive enzymes, the sensor produces an optical shift discernible to the naked eye. The diagnostic efficacy and clinical applicability of these sensors are demonstrated using clinical samples from 32 patients, yielding a Receiver Operating Characteristic Area Under the Curve (ROC AUC) of 1.0. This work has the potential to significantly contribute to improved patient outcomes through continuous monitoring and early, low‐cost, and reliable AL detection. Anastomotic leakage (AL) is the leaking of pathogenic, non‐sterile gastrointestinal contents into the abdominal cavity of a patient, with mortality rates of up to 27%. In this work, a naked eye‐readable, electronic‐free sensor for the continuous monitoring of drain fluid enzymes and early detection of AL is introduced.

Postoperative anastomotic leaks are the most feared complications after gastric surgery. For diagnostics clinicians mostly rely on clinical symptoms such as fever and tachycardia, often developing as a result of an already fully developed, i.e., symptomatic, surgical leak. A gastric fluid responsive, dual modality, electronic‐free, leak sensor system integrable into surgical adhesive suture support materials is introduced. Leak sensors contain high atomic number carbonates embedded in a polyacrylamide matrix, that upon exposure to gastric fluid convert into gaseous carbon dioxide (CO2). CO2 bubbles remain entrapped in the hydrogel matrix, leading to a distinctly increased echogenic contrast detectable by a low‐cost and portable ultrasound transducer, while the dissolution of the carbonate species and the resulting diffusion of the cation produces a markedly reduced contrast in computed tomography imaging. The sensing elements can be patterned into a variety of characteristic shapes and can be combined with nonreactive tantalum oxide reference elements, allowing the design of shape‐morphing sensing elements visible to the naked eye as well as artificial intelligence‐assisted automated detection. In summary, shape‐morphing dual modality sensors for the early and robust detection of postoperative complications at deep tissue sites, opening new routes for postoperative patient surveillance using existing hospital infrastructure is reported. Gastric leaks are a greatly feared postsurgical complication. Here dual modality ultrasound and computed tomography sensors for early gastric leak detection is presented. The electronic‐free sensors are fully integrable into adhesive surgical sealant patches as well as patternable, achieving shape morphing contrast changes under conditions of leak, therefore allowing for facile leak diagnostics.

Anastomotic leakage is a dreadful complication in colorectal surgery. It has a negative impact on postoperative mortality, long term life quality and oncological results. Nanofibrous polycaprolactone materials have shown pro-healing properties in various applications before. Our team developed several versions of these for healing support of colorectal anastomoses with promising results in previous years. In this study, we developed highly porous biocompatible polycaprolactone nanofibrous patches. We constructed a defective anastomosis on the large intestine of 16 pigs, covered the anastomoses with the patch in 8 animals (Experimental group) and left the rest uncovered (Control group). After 21 days of observation we evaluated postoperative changes, signs of leakage and other complications. The samples were assessed histologically according to standardized protocols. The material was easy to work with. All animals survived with no major complication. There were no differences in intestinal wall integrity between the groups and there were no signs of anastomotic leakage in any animal. The levels of collagen were significantly higher in the Experimental group, which we consider to be an indirect sign of higher mechanical strength. The material shall be further perfected in the future and possibly combined with active molecules to specifically influence the healing process.

Decellularized scaffolds can serve as an excellent three-dimensional environment for cell repopulation. They maintain tissue-specific microarchitecture of extracellular matrix proteins with important spatial cues for cell adhesion, migration, growth, and differentiation. However, criteria for quality assessment of the three-dimensional structure of decellularized scaffolds are rather fragmented, usually study-specific, and mostly semi-quantitative. Thus, we aimed to develop a robust structural assessment system for decellularized porcine liver scaffolds. Five scaffolds of different quality were used to establish the new evaluation system. We combined conventional semi-quantitative scoring criteria with a quantitative scaffold evaluation based on automated image analysis. For the quantitation, we developed a specific open source software tool (ScaffAn) applying algorithms designed for texture analysis, segmentation, and skeletonization. ScaffAn calculates selected parameters characterizing structural features of porcine liver scaffolds such as the sinusoidal network. After evaluating individual scaffolds, the total scores predicted scaffold interaction with cells in terms of cell adhesion. Higher scores corresponded to higher numbers of cells attached to the scaffolds. Moreover, our analysis revealed that the conventional system could not identify fine differences between good quality scaffolds while the additional use of ScaffAn allowed discrimination. This led us to the conclusion that only using the combined score resulted in the best discrimination between different quality scaffolds. Overall, our newly defined evaluation system has the potential to select the liver scaffolds most suitable for recellularization, and can represent a step toward better success in liver tissue engineering.