Search

Background: Intestinal vaginoplasty can be performed as vaginal reconstruction procedure. Aa pedicled intestinal segment is isolated and transferred to the (neo)vaginal cavity to form the neovaginal lining. Case: A 38-year old patient with Fanconi anemia and congenital vaginal absence, who underwent sigmoid vaginoplasty at the age of one, visited the outpatient clinic with a palpable neovaginal mass. At MRI examination, a neovaginal tumor was observed of approximately 25 × 10 mm without lymphadenopathy, which turned out to be a mucinous adenocarcinoma (T3N0M0). She underwent excision of the total mesocolon, including the sigmoid neovagina, coloanal anastomosis and anus. Summary and Conclusion: Postoperative cancer surveillance seems justified after sigmoid vaginoplasty, even more so in patients with a (genetically) high risk of developing cancer and/or with a history of malignancy.

BackgroundOne mechanism that can explain the link between processed meat consumption and colorectal cancer (CRC) is the production of carcinogenic N-nitroso compounds (NOCs) in the gastrointestinal tract. Oral and gut microbes metabolize ingested proteins (a source of secondary and tertiary amines and amides) and can reduce nitrate to nitrite, generating potentially carcinogenic NOCs.ObjectiveWe evaluated whether nitrate/nitrite in processed meat or water influences the fecal or salivary microbiota.DesignIn this dietary intervention study, 63 volunteers consumed diets high in conventional processed meats for two weeks, switched to diets high in poultry for two weeks, and then consumed phytochemical-enriched conventional processed or low-nitrite processed meat diets for two weeks. During the intervention, they drank water with low nitrate concentrations and consumed a healthy diet with low antioxidants. Then the volunteers drank nitrate-enriched water for 1 week, in combination with one of the four different diets. We measured creatinine-adjusted urinary nitrate levels and characterized the oral and fecal microbiota using 16S rRNA amplicon sequencing.ResultsUsing linear mixed models, we found that, compared to baseline, urinary nitrate levels were reduced during the phytochemical-enriched low-nitrite meat diet (p-value = 0.009) and modestly during the poultry diet (p-value = 0.048). In contrast, urinary nitrate increased after 1-week of drinking nitrate-enriched water (p-value

An increasing number of farmland initiatives aim to aid biodiversity conservation through alternative farming practices such as nature-inclusive farming. However, these approaches frequently lead to trade-offs between biodiversity conservation and crop yield. For example, buckwheat (Fagopyrum esculentum) is a melliferous crop that flowers for a long period in the summer when nectar in agricultural areas is generally scarce, and buckwheat cultivation could therefore contribute to wild pollinator conservation. However, honeybees (Apis mellifera) are placed to ensure sufficient crop pollination, which potentially increases resource competition with wild pollinators in and around the crop. Here, we have studied this trade-off by surveying pollinators in and around 16 small-scale (∼1 ha) flowering buckwheat fields and we determined the contribution of pollinator density to crop yield in a nature-inclusive farming project. We found that the buckwheat pollinator community was diverse, albeit dominated by honeybees. We found no clear indications of resource competition between honeybees and wild pollinators within the buckwheat fields. Honeybee density in the surroundings was generally low, and increased minimally during honeybee-hive placement. While densities of honeybees decreased non-linearly over the day in buckwheat fields, they did not (temporarily) move into the surroundings of the field, suggesting limited competition for resources with wild pollinators. Crop yield was largely dependent on crop pollinator density, notably of honeybees, and to a lesser extent crop biomass (as a proxy for agricultural management). Our results show that buckwheat cultivation fits well within nature-inclusive farming if some simple precautionary measures are being taken, such as limiting the honeybee-hive densities and placing hives only during the main flowering period. The introduction of buckwheat cultivation into crop rotation could then contribute to fill an important nectar gap in the summer, which potentially boosts wild pollinator populations in the long term.

Abstract The thiopurine derivatives azathioprine (AZA), mercaptopurine (MP) and tioguanine (TG) remain standard treatment of inflammatory bowel disease (IBD). The immune suppressive effect of thiopurines is primarily based on blocking the Ras-related C3 botulinum toxin substrate 1 (Rac1) causing apoptosis of T lymphocytes by inhibition of the phosphorylated downstream transcription factor Signal Transducer and Activator of Transcription 3 (pSTAT3). A functional pharmacodynamic marker in T lymphocytes may be useful to predict therapeutic outcome of thiopurine therapy. The aim of this study was to explore whether protein levels of Rac1 and pSTAT3 in T lymphocytes may be applied as a specific pharmacodynamic marker for thiopurine therapy in IBD patients. Rac1 and pSTAT3 protein levels in T lymphocytes were explored in 57 IBD patients (median age 51 years, 56% female), subdivided into six groups based on IBD activity and its treatment: patients with active disease without IBD maintenance medication (1) or patients in remission on AZA/MP (2), TG (3), infliximab (IFX) (4), thiopurine and IFX combination-treatment (5) or without IBD medication (6). Reference values were obtained from healthy subjects. Rac1 and pSTAT3 protein levels in T lymphocytes from patients on thiopurine monotherapy (group 2 and 3) were compared to the other groups, and to healthy subjects. Absolute Rac1 and pSTAT3 protein levels showed no differences between the thiopurine monotherapy groups when compared to patients with active disease. However, the ratio of Rac1 and pSTAT3 protein levels was lower in thiopurine patients groups compared to patients with active disease. Rac1-corrected pSTAT3 protein levels may serve as a pharmacodynamic marker of thiopurine monotherapy and may be a potential tool to predict therapeutic effectiveness in IBD patients.

Abstract Background Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C. Methods/design Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. Discussion PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente et al., 2007; Bassi et al., 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., 2016; Pratt et al., 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., 2022; Asbun and Stauffer, 2011).

Objective: To develop a prediction model for major morbidity and endocrine dysfunction after central pancreatectomy (CP) which could help in tailoring the use of this procedure. Background: CP is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and premalignant tumors in the body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared with distal pancreatectomy but it is thought to increase the risk of short-term complications, including postoperative pancreatic fistula (POPF). Methods: International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010-2021). The primary endpoint was major morbidity. Secondary endpoints included POPF grade B/C, endocrine dysfunction, and the use of pancreatic enzymes. Two risk models were designed for major morbidity and endocrine dysfunction utilizing multivariable logistic regression and internal and external validation. Results: A total of 838 patients after CP were included [301 (36%) minimally invasive] and major morbidity occurred in 248 (30%) patients, POPF B/C in 365 (44%), and 30-day mortality in 4 (1%). Endocrine dysfunction in 91 patients (11%) and use of pancreatic enzymes in 108 (12%). The risk model for major morbidity included male sex, age, Body Mass Index, and American Society of Anesthesiologists score =3. The model performed acceptably with an area under the curve of 0.72 (CI: 0.68-0.76). The risk model for endocrine dysfunction included higher Body Mass Index and male sex and performed well [area under the curve: 0.83 (CI: 0.77-0.89)]. Conclusions: The proposed risk models help in tailoring the use of CP in patients with symptomatic benign and premalignant lesions in the body and neck of the pancreas (readily available through www. pancreascalculator.com). [ABSTRACT FROM AUTHOR]

Aims: Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6‐thioguanine nucleotides (6‐TGN), 6‐methylmercaptopurine ribonucleotides (6‐MMPR) and the 6‐MMPR/6‐TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes. Methods: A post‐hoc analysis was conducted of a multicentre, prospective, observational study on thiopurine‐induced hepatotoxicity. IBD patients who initiated thiopurine therapy were included and thiopurine metabolite concentrations were assessed after 7 days (±1) (T1). Patients were monitored for 12 weeks to document the occurrence of ADRs, early treatment discontinuation and effectiveness. Results: In total, 181 patients were evaluated. At T1, 6‐MMPR concentrations and 6‐TGN/6‐MMPR ratios were independently related to treatment discontinuation within 12 weeks after correction for sex, age and body mass index (BMI) (P =.034 and.002, respectively). The largest effects were observed for 6‐MMPR ≥3000 pmol/8 × 108 RBC and 6‐TGN/6‐MMPR ratio ≥17. Furthermore, 6‐MMPR concentrations and 6‐TGN/6‐MMPR ratios at T1 were independently related to skewed metabolism at steady state (Week 8, 6‐MMPR/‐6TGN ratio ≥11 and ≥20) (both P <.001). The occurrence of ADRs and effectiveness were not independently related to T1 thiopurine metabolite concentrations. Conclusions: Thiopurine metabolite concentrations at T1 were related to early treatment discontinuation and skewed metabolism at steady state, but not to effectiveness, helping to identify patients with a high risk of thiopurine treatment failure. [ABSTRACT FROM AUTHOR]

Aim: To identify patient‐reported complaints affecting quality of life in Crohn's disease patients with a perianal fistula, and to compare differences between subgroups. Method: A questionnaire was distributed to 1667 patients from the Dutch Crohn's and Colitis Patients' organization, those patients with Crohn's disease and perianal fistula were included. Patients were asked to report (using free text) their most important fistula‐related complaints affecting their quality of life. All responses were structurally analyzed and categorized. Data comparisons were made between subgroups: women versus men, patients with versus without current presence of a seton, and patients aged ≤40 versus >40 years. Results: Of 743 respondents (44.6%), 123 patients with Crohn's disease and perianal fistula were included (92 women, median age 41 years [IQR 34–56] and 36 with seton). A total of 776 complaints were allocated to 36 categories, with 19 reported in >10% of patients. Perianal fistula‐related complaints affected nearly all patients (95.9%). Impact on psychological status (71.7% vs. 29.0%; p < 0.0001) and on sexual activities (37.0% vs. 16.1%; p = 0.003) were more common in women than men. Younger patients more often reported insecurity (38.7% vs. 18.0%; p = 0.026), shame (29.0% vs. 11.5%; p = 0.024), and impact on sexual activities (40.3% vs. 23.0%; p = 0.048) than older patients. Patients with a seton more frequently reported self‐experienced malodour (50.0% vs. 23.0%; p = 0.005), physical activity limitations (41.7% vs. 19.5%; p = 0.014), and work/study impact (22.2% vs. 5.7%; p = 0.019). Conclusion: We identified 19 perianal fistula‐related complaints reported by >10% of patients. These complaints may guide improvement of current outcome measures. [ABSTRACT FROM AUTHOR]

Summary: The ex vivo organotypic brain slice invasion model is commonly used to study the growth dynamics of gliomas, primary brain tumors that are known for their invasive behavior. Here, we describe a protocol where the ex vivo organotypic mouse brain slice invasion model is combined with whole-mount immunostaining, tissue clearing, and 3D reconstruction, to visualize and quantify the invasion of glioma cells. In addition, we describe an approach to determine the proliferation rate of the cells within this model.For complete details on the use and execution of this protocol, please refer to Uceda-Castro et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Tioguanine is metabolised by fewer enzymatic steps compared to azathioprine and mercaptopurine, without generating 6-methylmercaptopurine ribonucleotides. However, thiopurine S-methyl transferase (TPMT) plays a role in early toxicity in all thiopurines. We aimed to describe the hazards and opportunities of tioguanine use in inflammatory bowel disease (IBD) patients with aberrant TPMT metabolism and propose preventative measures to safely prescribe tioguanine in these patients. In this retrospective cohort study, all determined TPMT genotypes (2016–2021) were evaluated for aberrant metabolism (i.e., intermediate and poor TPMT metabolisers). Subsequently, all IBD patients on tioguanine with aberrant TPMT genotypes were evaluated for tioguanine dosages, adverse drug events, lab abnormalities, treatment duration and effectiveness. TPMT genotypes were determined in 485 patients, of whom, 50 (10.3%) and 4 patients (0.8%) were intermediate and poor metabolisers, respectively. Of these patients, 12 intermediate and 4 poor TPMT metabolisers had been prescribed tioguanine in varying doses. In one poor TPMT metaboliser, tioguanine 10 mg/day induced delayed pancytopenia. In general, reduced tioguanine dosages of 5 mg/day for intermediate TPMT metabolisers, and 10 mg two-weekly for poor TPMT metabolisers, resulted in a safe, long-term treatment strategy. Diminished or absent TPMT enzyme activity was related with a pharmacokinetic shift of tioguanine metabolism which is associated with relatively late-occurring myelotoxicity in patients on standard tioguanine dose. However, in strongly reduced dose regimens with strict therapeutic drug and safety monitoring, tioguanine treatment remained a safe and effective option in IBD patients with dysfunctional TPMT.

Purpose: Coronectomy is a valuable treatment proven safe for non-pathological mandibular third molars with an increased risk of inferior alveolar nerve injury. Coronectomy may also be useful for mandibular third molars with dentigerous cysts and caries, but this is not commonly performed due to the lack of well-designed, evidence-based studies. Here, we aim to investigate the safety of coronectomy for mandibular third molars with caries and dentigerous cysts. Methods: One hundred fifteen patients with an impacted mandibular third molar with a dentigerous cyst or caries underwent coronectomy or complete removal and received follow-up with clinical and radiographical examinations. We statistically compared the presence of postoperative complications after coronectomy versus complete removal. Results: Data from 121 molars were available for analysis. The results revealed no significant difference in the occurrence of postoperative complications (including persistent pain, inferior alveolar nerve injury, infection, alveolar osteitis, excessive bleeding, and the need for retreatment) between coronectomy and complete removal. Additionally, the incidence of postoperative complications was not related to any analyzed patient- or molar-related factors, including age, gender, health status, smoking, caries, dentigerous cyst extent, and impaction degree. Conclusion: For pathological impacted mandibular third molars with dentigerous cysts and caries, coronectomy exhibited both short-term and long-term safety, showing no significant difference in postoperative complications compared to total removal. Our results suggest that coronectomy can be indicated for pathological mandibular third molars with proximity to the inferior alveolar nerve. Trial registration number: Not applicable. [ABSTRACT FROM AUTHOR]

Abstract Background During the COVID-19 pandemic, a decrease in the number of patients presenting with acute appendicitis was observed. It is unclear whether this caused a shift towards more complicated cases of acute appendicitis. We compared a cohort of patients diagnosed with acute appendicitis during the 2020 COVID-19 pandemic with a 2019 control cohort. Methods We retrospectively included consecutive adult patients in 21 hospitals presenting with acute appendicitis in a COVID-19 pandemic cohort (March 15 – April 30, 2020) and a control cohort (March 15 – April 30, 2019). Primary outcome was the proportion of complicated appendicitis. Secondary outcomes included prehospital delay, appendicitis severity, and postoperative complication rates. Results The COVID-19 pandemic cohort comprised 607 patients vs. 642 patients in the control cohort. During the COVID-19 pandemic, a higher proportion of complicated appendicitis was seen (46.9% vs. 38.5%; p = 0.003). More patients had symptoms exceeding 24 h (61.1% vs. 56.2%, respectively, p = 0.048). After correction for prehospital delay, presentation during the first wave of the COVID-19 pandemic was still associated with a higher rate of complicated appendicitis. Patients presenting > 24 h after onset of symptoms during the COVID-19 pandemic were older (median 45 vs. 37 years; p = 0.001) and had more postoperative complications (15.3% vs. 6.7%; p = 0.002). Conclusions Although the incidence of acute appendicitis was slightly lower during the first wave of the 2020 COVID-19 pandemic, more patients presented with a delay and with complicated appendicitis than in a corresponding period in 2019. Spontaneous resolution of mild appendicitis may have contributed to the increased proportion of patients with complicated appendicitis. Late presenting patients were older and experienced more postoperative complications compared to the control cohort.

There are limited data on therapeutic drug monitoring (TDM) in inflammatory bowel disease (IBD) patients treated with vedolizumab (VDZ). Although an exposure–response relation has been demonstrated in the post-induction phase, this relationship is more uncertain in the maintenance phase of treatment. The aim of our study was to determine whether there is an association between VDZ trough concentration and clinical and biochemical remission in the maintenance phase. A prospective, observational multicenter study has been performed on patients with IBD on VDZ in the maintenance treatment (≥14 weeks). Patient demographics, biomarkers, and VDZ serum trough concentrations were collected. Clinical disease activity was scored by the Harvey Bradshaw Index (HBI) for Crohn’s disease (CD) and the Simple Clinical Colitis Activity Index (SCCAI) for ulcerative colitis (UC). Clinical remission was determined as HBI < 5 and SCCAI < 3. Biochemical remission was defined as fecal calprotectin p = 0.019). In this population, higher trough VDZ concentrations were associated with biochemical remission but not with clinical remission.