Multilayer fibroin/chitosan oligosaccharide lactate and pullulan immunomodulatory patch for treatment of hernia and prevention of intraperitoneal adhesion.

This study aims to develop a novel intraperitoneal two- or three-layered patch with immunomodulatory property for treatment of hernia, regeneration of abdominal wall and prevention of intraperitoneal adhesions. Polypropylene (PP) mesh, middle layer, was intended to provide mechanical support whereas pullulan (PUL) hydrogel coating layer was designed to prevent intraperitoneal adhesions. Fibroin/chitosan oligosaccharide lactate (F/COS) layer electrospun on one side of pullulan was chosen for immunomodulation and abdominal wall regeneration. Physical and mechanical properties and regenerative capacity of intraperitoneal patches were determined. Immunomodulatory property of electrospun layer and whole patch was studied by determining nitric oxide amount produced by RAW 264.7 macrophages. 25 % (w/v) PUL hydrogel and F/COS with 90:10 (w/w) ratio yielded optimal results. Here, we report that fabricated intraperitoneal patches successfully prevented cell adhesion on one side and increased cell viability and proliferation on other side, along with immunomodulation, in vitro.

Fibroblast activation protein inhibitor (FAPI) PET for diagnostics and advanced targeted radiotherapy in head and neck cancers.

PURPOSE: Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) have been associated with the aggressive nature of head and neck cancers (HNCs). These tumours grow diffusely, leading to extremely challenging differentiation between tumour and healthy tissue. This analysis aims to introduce a novel approach of tumour detection, contouring and targeted radiotherapy of HNCs using visualisation of CAFs: PET-CT with 68Ga-radiolabeled inhibitors of FAP (FAPI). METHODS: FAPI PET-CT was performed without complications prior to radiotherapy in addition to contrast enhanced CT (CE-CT) and MRI on 14 patients with HNC. First, for tissue biodistribution analysis, volumes of interest were defined to quantify SUVmean and SUVmax in tumour and healthy parenchyma. Secondly, using four thresholds of three-, five-, seven- and tenfold increase of FAPI enhancement in the tumour as compared with normal tissue, four different gross tumour volumes (FAPI-GTV) were created automatically. These were compared with GTVs created conventionally with CE-CT and MRI (CT-GTV). RESULTS: The biodistribution analysis revealed high FAPI avidity within tumorous lesions (e.g. primary tumours, SUVmax 14.62 ± 4.44; SUVmean 7.41 ± 2.39). In contrast, low background uptake was measured in healthy tissues of the head and neck region (e.g. salivary glands: SUVmax 1.76 ± 0.31; SUVmean 1.23 ± 0.28). Considering radiation planning, CT-GTV was of 27.3 ml, whereas contouring with FAPI resulted in significantly different GTVs of 67.7 ml (FAPI × 3, p = 0.0134), 22.1 ml (FAPI × 5, p = 0.0419), 7.6 ml (FAPI × 7, p = 0.0001) and 2.3 ml (FAPI × 10, p = 0.0001). Taking these significant disparities between the GTVs into consideration, we merged FAPI-GTVs with CT-GTVs. This resulted in median volumes, that were, as compared to CT-GTVs, significantly larger with FAPI × 3 (54.7 ml, + 200.5% relative increase, p = 0.0005) and FAPI × 5 (15.0 ml, + 54.9%, p = 0.0122). Furthermore, FAPI-GTVs were not covered by CE-CT-based planning target volumes (CT-PTVs) in several cases. CONCLUSION: We present first evidence of diagnostic and therapeutic potential of FAPI ligands in head and neck cancer. Larger studies with histopathological correlation are required to validate our findings.

Prospective phase-II-study evaluating postoperative radiotherapy of cervical and endometrial cancer patients using protons - the APROVE-trial.

BACKGROUND: The prognosis for patients with cervical or endometrial cancer has improved over the last decades. Thus, reducing therapy-related toxicity and impact on quality of life have become more and more important. With the development of new radiotherapy techniques like IMRT (Intensity-modulated radiotherapy) the incidence of acute and chronic toxicities has already been reduced. Nevertheless, rates of complications requiring medical treatment range from 0.7-8% according to literature. 7.7% of patients develop severe complications after 5 years with an increasing risk for complications of 0.3%/year. Particularly, the volume of the small and large bowel receiving low doses (15 Gy) has been shown to be a predictive factor for the development of higher bowel toxicity. With the introduction of proton therapy into clinical practice, there are new opportunities for optimization of organ at risk-sparing thus possibly reducing toxicity. METHODS/DESIGN: The APROVE study is a prospective single-center one-arm phase-II-study. Patients with cervical or endometrial cancer after surgical resection who have an indication for postoperative pelvic radiotherapy will be treated with proton therapy instead of the commonly used photon radiation. A total of 25 patients will be included in this trial. Patients will receive a dose of 45-50.4 GyE in 1.8 GyE fractions 5-6 times per week using active raster-scanning pencil beam proton radiation. Platinum-based chemotherapy can be administered if indicated. For treatment planning, rectum, sigma, large and small bowel, bladder and femoral heads are defined as organs at risk. The CTV is defined according to the RTOG consensus guidelines. DISCUSSION: The primary endpoint of the study is the evaluation of safety and treatment tolerability of pelvic radiation using protons defined as the lack of any CTC AE Grade 3 or 4 toxicity. Secondary endpoints are clinical symptoms and toxicity, quality of life and progression-free survival. The aim is to explore the potential of proton therapy as a new method for adjuvant pelvic radiotherapy to decrease the dose to the bowel, rectum and bladder thus reducing acute and chronic toxicity and improving quality of life. TRIAL REGISTRATION: Registered at https://clinicaltrials.gov , ClinicalTrials.gov Identifier: NCT03184350 , registered 09 June 2017, enrolment of the first participant 19 June 2017.

Does thromboprophylaxis cause bleeding after laparoscopic cholecystectomy?

OBJECTIVES: This study reports the results of a single center experience on the use of pharmacological venous thromboembolism (VTE) prophylaxis in laparoscopic cholecystectomy patients. BACKGROUND: The prevention of VTE is of crucial importance in surgical practice. However, the severity of thromboembolism risk and the necessity of thromboprophylaxis for laparoscopic cholecystectomy is still being debated. METHODS: The data of the patients, who underwent laparoscopic cholecystectomy for symptomatic cholelitiasis in a single center between the years 2005 and 2015 were analysed retrospectively for incidents of symptomatic VTE and bleeding complications. Fisher Exact Test was used to compare the outcomes of the patients who did and did not receive thromboprophylaxis. RESULTS: Of the 1485 patients who were included in the study, 307 (20.67 %) having a low VTE risk, did not receive any thromboprophylaxis; while 1178 (79.33 %) with a medium, high or a very high risk received VTE prophylaxis. A bleeding complication occurred in 14 (1.18 %) patients receiving prophylaxis and in 2 (0.65 %) patients not receiving prophylaxis (p = 0.548). No patients in this study experienced clinically symptomatic VTE. CONCLUSIONS: The findings of this study indicate that the selective use of thromboprophylaxis does not significantly increase the risk of bleeding after laparoscopic cholecystectomy and probably decreases the incidence of symptomatic thrombotic complications (Ref. 18) Keywords: laparoscopic cholecystectomy, bleeding, venous thromboemboly, prophylaxis, low molecular weight heparin.

Is a routine preoperative rectosigmoidoscopy necessary in patients with bilateral inguinal hernia?

OBJECTIVES: The purpose of this prospective study was to evaluate the association between bilateral inguinal hernias and colorectal cancers. PURPOSE: Inguinal hernias are one of the most common subjects in surgical practice and have been known to be associated with some other pathologies since 1831. Although there are some series in literature reporting the association of colorectal cancers with inguinal hernias, it is still controversial to perform colorectal diagnostic tools in hernia patients. Colorectal cancers are particularly accused to be in association with synchronous bilateral hernias as they increase the intra-abdominal pressure. METHODS: Rectosigmoidoscopy was performed in 110 consecutive bilateral hernia patients and the results were recorded prospectively. Patients having colorectal diseases were excluded. RESULTS: There were no pathologies in 87 (%79,1) rectosigmoidoscopies, while benign pathologies (hemorrhoids, polyps and diverticulitis) were diagnosed in 23 (%20,9). CONCLUSIONS: It has not been proved yet that colorectal cancers increase the incidence of bilateral inguinal hernias. The incidence of benign pathologies in our series was similar to that of same age population without hernia. As a conclusion of this study we believe that rectosigmoidoscopy is not necessary for synchronous bilateral hernias unless the patient has any complaints or risk factors. Colorectal screening tools are performed when the clinical findings or the story of the patient support colorectal cancers) (Tab. 1, Ref. 25).