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Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007–2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007–2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0–146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.

The efficacy and safety of antibiotic treatment for uncomplicated acute appendicitis has been established at long-term follow-up with the majority of recurrences shown to occur within the first year. Overall costs of antibiotics are significantly lower compared with appendectomy at short-term follow-up, but long-term durability of these cost savings is unclear. The study objective was to compare the long-term overall costs of antibiotic therapy versus appendectomy in the treatment of uncomplicated acute appendicitis in the APPAC (APPendicitis ACuta) trial at 5 years. This multicentre, non-inferiority randomized clinical trial randomly assigned 530 adult patients with CT-confirmed uncomplicated acute appendicitis to appendectomy or antibiotic treatment at six Finnish hospitals. All major costs during the 5-year follow-up were recorded, whether generated by the initial visit and subsequent treatment or possible recurrent appendicitis. Between November 2009 and June 2012, 273 patients were randomized to appendectomy and 257 to antibiotics. The overall costs of appendectomy were 1.4 times higher (p<0.001) (€5716; 95% CI: €5510 to €5925) compared with antibiotic therapy (€4171; 95% CI: €3879 to €4463) resulting in cost savings of €1545 per patient (95% CI: €1193 to €1899; p<0.001) in the antibiotic group. At 5 years, the majority (61%, n = 156) of antibiotic group patients did not undergo appendectomy. At 5-year follow-up antibiotic treatment resulted in significantly lower overall costs compared with appendectomy. As the majority of appendicitis recurrences occur within the first year after the initial antibiotic treatment, these results suggest that treating uncomplicated acute appendicitis with antibiotics instead of appendectomy results in lower overall costs even at longer-term follow-up.

PurposeAcute appendicitis may present as uncomplicated and complicated and these disease forms differ both epidemiologically and clinically. Complicated acute appendicitis has traditionally been defined as an appendicitis complicated by perforation or a periappendicular abscess, and an appendicolith represents a predisposing factor of complicated disease. There are histopathological differences between uncomplicated acute appendicitis and the previously established traditional forms of complicated acute appendicitis, but to our knowledge, the histopathological differences between uncomplicated acute appendicitis and complicated acute appendicitis presenting with an appendicolith have not yet been reported. The study purpose was to assess these differences with two prospective patient cohorts: (1) computed tomography (CT) confirmed uncomplicated acute appendicitis patients enrolled in the surgical treatment arm of the randomized APPAC trial comparing appendectomy with antibiotics for the treatment of uncomplicated acute appendicitis and (2) patients with CT-verified acute appendicitis presenting with an appendicolith excluded from the APPAC trial.MethodsThe following histopathological parameters were assessed: appendiceal diameter, depth of inflammation, micro-abscesses, density of eosinophils, and neutrophils in appendiceal wall and surface epithelium degeneration.ResultsUsing multivariable logistic regression models adjusted for age, gender, and symptom duration, statistically significant differences were detected in the depth of inflammation ≤ 2.8 mm (adjusted OR 2.18 (95%CI: 1.29–3.71, p = 0.004), micro-abscesses (adjusted OR 2.16 (95%CI: 1.22–3.83, p = 0.008), the number of eosinophils and neutrophils ≥ 150/mm2 (adjusted OR 0.97 (95%CI: 0.95–0.99, p = 0.013), adjusted OR 3.04 (95%CI: 1.82–5.09, p < 0.001, respectively).ConclusionsThese results corroborate the known clinical association of an appendicolith to complicated acute appendicitis.

Introduction Chronic pelvic pain (CPP) affects over one fifth of women worldwide, and endometriosis is one of the most common causes. In the present study, we examined whether sacral neuromodulation (SNM) is effective in the treatment of refractory chronic pelvic pain in women with endometriosis. Material and methods This multicenter prospective pilot study was started in 2017 and includes patients with chronic pelvic pain with no other obvious pathology than endometriosis. Other treatment options have been tried or they are unsuitable. Patients underwent SNM implantation. The main outcome was postoperative pain reduction and secondary outcome was quality of life. The following questionnaires were used to assess the outcomes: Brief pain inventory (BPI), clinical global impression ‐ improvement (CGI‐I), 15D‐measure of health‐related quality of life, and Biberoglu and Behrman (B&B) score. Results A total of 35 patients underwent the SNM procedure and, at the time of analysis, 15 patients had returned one‐year questionnaires. The patients had a history of endometriosis for a median of 5.5 (interquartile range 2–9) years, with no correlation between the severity of symptoms and the duration of the disease (p = 0.158). A total of 31 patients (89%) were implanted with the internal pulse generator. There were statistically significant changes in BPI pain‐related items. Worst experienced daily pain decreased among those who returned 12‐month questionnaires from median 9 to 5 (p = 0.006), average daily pain from 6 to 3.5 (p = 0.004), and least daily pain from 3 to 1 (p = 0.004). Based on the CGI questionnaire (n = 14), at 12 months nine patients (60%) experienced great improvement in their symptoms, three patients (20%) much improvement and two patients (13%) minimal improvement. None of the patients experienced worsening of their symptoms. There was a statistically significant change in overall 15D score at 1 month (p < 0.001), 6 months (p = 0.001) and 12 months (p = 0.018), when the results were compared to baseline values. Median B&B score also improved significantly and decreased from a baseline value of 8 (4–12) to 4.5 (0–6), p = 0.002. Conclusions Based on the preliminary findings of our study, SNM might be a promising treatment of CPP in endometriosis patients. The treatment of chronic pelvic pain related to endometriosis is difficult and the mainstream remain medical therapy and surgery. Based on the preliminary findings of our study, it appears that SNM is a promising treatment option of CPP in endometriosis patients that do not respond to conventional therapies.

Dysregulated metabolism, a hallmark of cancer, creates unique metabolic features that can be employed to elucidate cancer prognosis, personalized treatment, and therapeutic response. Metabolomics has emerged as a powerful tool for profiling biomarkers in cancer studies. Most cancer metabolomic research on extracellular vesicles (EVs) has focused on human biofluids as samples. The metabolome of fecal EVs, a connecting link for host-microbiome interactions in cancer, has not been extensively studied. In this controlled study, we investigated the metabolomic signatures of fecal EVs in patients with solid tumors. Fecal samples were collected from adult patients with solid tumors ( n  = 28) and healthy controls ( n  = 7). After the isolation of EVs from fecal samples, EV metabolites were identified using targeted metabolomics profiling based on liquid chromatography-mass spectrometry (LC-MS). The metabolomic profiles of the fecal EVs from both patients and controls were compared using R and Metabolite Set Enrichment Analysis was done using Metaboanalyst 6.0. The metabolomic profiles of fecal EVs showed several differences between patients with solid tumors and control subjects. L-glutamic acid was identified as the most significantly enriched metabolite in patients with solid tumors. Conversely, guanine and N-acetylneuraminate were the most significantly depleted metabolites in the fecal EVs of these patients. Metabolite Set Enrichment Analysis linked the identified EV metabolites to key metabolic pathways, including arginine biosynthesis, glyoxylate and dicarboxylate metabolism, and the biosynthesis of branched-chain amino acids and unsaturated fatty acids. Receiver operating characteristic (ROC) revealed that glutamic acid is the most effective metabolite in distinguishing cancer patients from healthy controls. Some of these metabolites may also have plausible bacterial origins, as described in previous studies. Distinct metabolic phenotypes were identified in patients with solid tumors by analyzing fecal EVs in this study. The metabolomic profiling of fecal EVs offers valuable insights into the interactions between the gut microbiome and the host as well as unique metabolic snapshot of the disease status in the context of cancer. Thus, fecal EVs should be included in advanced multi-omics analyses of cancer research, alongside other human biofluids.

ObjectiveTo assess the feasibility and evaluate the performance of a relaunched colorectal cancer (CRC) screening programme with different cut-offs for men and women.DesignPopulation-based registry study.SettingNine municipalities in Finland which started CRC screening with faecal immunochemical test (FIT) in April 2019 with cut-off levels 70 µg Hg/g faeces for men and 25 µg Hg/g faeces for women.ParticipantsMen (n=13 059) and women (n=14 669) aged 60–66 years invited to screening during the first programme year.Outcome measuresParticipation rates, positivity rates, detection rates of CRC and advanced adenoma (AA), and positive predictive values (PPV) of FIT for CRC and AA.ResultsAltogether 21 993 invitees returned stool samples. The participation rate of women (83.4%; 95% CI 82.8 to 84.0) was significantly higher than that of men (74.7%; 95% CI 73.9 to 75.4). The positivity rates were 2.4% (2.2 to 2.7) and 2.8% (2.5 to 3.1), respectively. In total, 37 CRCs and 116 AAs were detected. The detection rates of CRC and AA per 1000 participants were 1.8 (1.1 to 2.9) and 7.2 (5.6 to 9.1) for men and 1.6 (0.9 to 2.4) and 3.8 (2.8 to 5.0) for women. The PPVs per 100 positive tests were 6.6 (4.0 to 10.3) and 25.7 (20.6 to 31.4) for men and 6.4 (3.9 to 9.8) and 15.5 (11.6 to 20.2) for women.ConclusionsThe chosen FIT strategy narrowed the gap in the diagnostic performance between men and women especially in the detection of CRC. The participation rates were excellent. The levels of positivity and detection rates were moderate and need further action. The results indicate that gender-specific protocols can be introduced to organised CRC screening. It is yet to be seen whether they are more effective than a uniform screening protocol.

PurposeLaparoscopic incisional ventral hernia repair (LIVHR) is often followed by seroma formation, bulging and failure to restore abdominal wall function. These outcomes are risk factors for hernia recurrence, chronic pain and poor quality of life (QoL). We aimed to evaluate whether LIVHR combined with defect closure (hybrid) follows as a diminished seroma formation and thereby has a lower rate of hernia recurrence and chronic pain compared to standard LIVHR.MethodsThis study is a multicentre randomised controlled clinical trial. From November 2012 to May 2015, 193 patients undergoing LIVHR for primary incisional hernia with fascial defect size from 2 to 7 cm were recruited in 11 Finnish hospitals. Patients were randomised to either a laparoscopic (LG) or a hybrid (HG) repair group. The main outcome measure was hernia recurrence, evaluated clinically and radiologically at a 1-year follow-up visit. At the same time, chronic pain scores and QoL were also measured.ResultsAt the 1-year-control visit, we found no difference in hernia recurrence between the study groups. Altogether, 11 recurrent hernias were found in ultrasound examination, producing a recurrence rate of 6.4%. Of these recurrences, 6 (6.7%) were in the LG group and 5 (6.1%) were in the HG group (p > 0.90). The visual analogue scores for pain were low in both groups; the mean visual analogue scale (VAS) was 1.5 in LG and 1.4 in HG (p = 0.50). QoL improved significantly comparing preoperative status to 1 year after operation in both groups since the bodily pain score increased by 7.8 points (p < 0.001) and physical functioning by 4.3 points (p = 0.014).ConclusionLong-term follow-up is needed to demonstrate the potential advantage of a hybrid operation with fascial defect closure. Both techniques had low hernia recurrence rates 1 year after operation. LIVHR reduces chronic pain and physical impairment and improves QoL.Trial Registry: Clinical trial number NCT02542085.

Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is a multifaceted, cytokine-like bioactive molecule whose levels are elevated in a wide range of inflammatory diseases and are associated with prognosis. Additionally, TIMP1 may play a role in driving systemic inflammation. TIMP1 immunohistochemistry and TIMP1 serum concentrations were analyzed in a cohort of 776 colorectal cancer patients. TIMP1 histoscore by cell type (tumor cell, other) was quantified using digital image analysis. Serum TIMP1 levels were evaluated for correlations with tumor TIMP1 expression, and their associations with tumor characteristics, inflammation, and prognosis were investigated. High serum TIMP1 concentrations associated with shorter overall survival (multivariable HR 1.85, 95% CI 1.30–2.65). Serum TIMP1 levels positively correlated with markers of systemic inflammation and tumor necrosis percentage but not with TIMP1 expression in tumor tissue. High TIMP1 intensity in tumor stroma associated with longer cancer-specific and overall survival in univariable analysis but not in multivariable models. T cell densities in tumor tissue positively correlated with tumor stromal TIMP1 expression and negatively with tumor epithelial TIMP1 expression. Serum TIMP1 levels show promise as a prognostic marker for colorectal cancer and correlate with systemic inflammatory markers, but do not correlate with TIMP1 expression in tumor tissue.

Background Incisional hernia is a frequent complication after loop-ileostomy closure, rationalizing hernia prevention. Biological meshes have been widely used in contaminated surgical sites instead of synthetic meshes in fear of mesh related complications. However, previous studies on meshes does not support this practice. The aim of Preloop trial was to study the safety and efficacy of synthetic mesh compared to a biological mesh in incisional hernia prevention after loop-ileostomy closure. Methods The Preloop randomized, feasibility trial was conducted from April 2018 until November 2021 in four hospitals in Finland. The trial enrolled 102 patients with temporary loop-ileostomy after anterior resection for rectal cancer. The study patients were randomized 1:1 to receive either a light-weight synthetic polypropylene mesh (Parietene Macro™, Medtronic) (SM) or a biological mesh (Permacol™, Medtronic) (BM) to the retrorectus space at ileostomy closure. The primary end points were rate of surgical site infections (SSI) at 30-day follow-up and incisional hernia rate during 10 months’ follow-up period. Results Of 102 patients randomized, 97 received the intended allocation. At 30-day follow-up, 94 (97%) patients were evaluated. In the SM group, 1/46 (2%) had SSI. Uneventful recovery was reported in 38/46 (86%) in SM group. In the BM group, 2/48 (4%) had SSI (p > 0.90) and in 43/48 (90%) uneventful recovery was reported. The mesh was removed from one patient in both groups (p > 0.90). Conclusions Both a synthetic mesh and biological mesh were safe in terms of SSI after loop-ileostomy closure. Hernia prevention efficacy will be published after the study patients have completed the 10 months’ follow-up.

IntroductionEndometriosis is a common gynaecological disease affecting around 10% of fertile-aged women, causing severe pain symptoms. Deep endometriosis is defined as endometriotic implants that infiltrate the underlying organs more than 5 mm in depth. Surgery for deep endometriosis requires advanced multidisciplinary surgical technique, often in very difficult surgical conditions, with increased risks of complications. Robotic surgery offers a high-definition three-dimensional view and articulating instruments that may allow more precise dissection than conventional laparoscopy in the pelvic area. The superiority of robotic surgery has not, however, been provedin randomised controlled studies, and there is a lack of long-term outcome data. Advanced endometriosis surgery offers an excellent platform to study the feasibility and long-term outcomes of robotic surgery compared with conventional laparoscopy.Methods and analysisROBEndo is a prospective, randomised, controlled clinical trial in a single-centre setting. Patients with deep endometriosis verified by MRI needing surgery at Oulu University Hospital (Oulu, Finland) will be considered eligible. 70 patients will be allocated 1:1 to receive either robotic-assisted or conventional laparoscopic surgery in two strata: radical surgery (with the removal of the uterus and adnexae) and gynaecological organ-sparing surgery. The primary outcome will be the surgical outcome as regards to pain symptoms measured on numeric rating scale (NRS) questionnaires at 24 hours and 6, 12 and 24 months postoperatively. As secondary outcomes, intraoperative measures, enhanced recovery after surgery factors, complications, cost and long-term quality of life measured with Endometriosis Health Profile-30 (EHP-30), Female Sexual Function Index (FSFI) and 15-dimensional (15D) questionnaires will be compared.Ethics and disseminationThis study has been approved by the Northern Ostrobothnian Hospital District Ethical Committee at Oulu University Hospital (212/2021). Informed consent will be obtained during the preoperative check-up by the operating gynaecologist. The results will be published in peer-reviewed international journals.Trial registration numberNCT05179109.