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Biliary complications are common after liver transplantation (LT). Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred method to treat biliary complications. Nevertheless, ERCP is not without complications and may have a greater complication rate in the LT population. Knowledge of the prevalence, severity, and possible risk factors for post‐ERCP pancreatitis (PEP) in LT recipients is limited. Therefore, this study aims to determine the incidence and severity of PEP and identify potential risk factors in LT recipients. This retrospective cohort included patients ≥18 years who underwent ≥1 ERCP procedures after LT between January 2010 and October 2021. Two hundred thirty‐two patients were included, who underwent 260 LTs and 1125 ERCPs. PEP occurred after 23 ERCP procedures (2%) with subsequent mortality in three (13%). Multivariate logistic regression identified wire cannulation of the pancreatic duct as a significant risk factor for PEP (OR, 3.21). The complication rate of PEP after LT in this study was shown to be low and is lower compared to patients without a history of LT. Nevertheless, the mortality rate of this group of patients was notably higher. [ABSTRACT FROM AUTHOR]

Background Confirming the diagnosis, invasiveness, and disease extent of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is challenging. The aim of this study was to summarize the literature on the efficacy and safety of peroral pancreatoscopy (POP) in the diagnosis of IPMN, including the impact of pre- and intraoperative POP on the management of IPMN. Methods The EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar databases were systematically searched for articles. Eligible articles investigated cohorts of patients who underwent POP for (suspected) IPMN. Results 25 articles were identified and included in this review; with 22 of these reporting on the diagnostic yield of POP in IPMN and 11 reporting on the effect of pre- or intraoperative POP on clinical decision-making. Cannulation and observation rates, and overall diagnostic accuracy were high across all studies. Frequently reported visual characteristics of IPMN were intraductal fish-egg-like lesions, hypervascularity, and granular mucosa. Overall, the adverse event rate was 12 %, primarily consisting of post-endoscopic retrograde cholangiopancreatography pancreatitis, with a pooled rate of 10 %, mostly of mild severity. Regarding the impact of POP on clinical decision-making, POP findings altered the surgical approach in 13 %–62 % of patients. Conclusion POP is technically successful in the vast majority of patients with (suspected) IPMN, has a consistently high diagnostic accuracy, but an adverse event rate of 12 %. Data on intraoperative pancreatoscopy are scarce, but small studies suggest its use can alter surgical management. Future studies are needed to better define the role of POP in the diagnostic work-up of IPMN. [ABSTRACT FROM AUTHOR]

Introduction: Duodenal stent placement is a palliative option for management of malignant gastric outlet obstruction (GOO). In the last 20 years, management of gastrointestinal cancers has considerably changed. It is unknown if these changes have affected clinical outcome of duodenal stent placement.Methods: Retrospective cohort study conducted in a tertiary referral center. Patients who underwent duodenal stent placement for GOO-symptoms due to a malignant stricture were included. Primary outcome was GOO-symptom free survival. Secondary outcomes included stent-related adverse event rates. Potential explanatory parameters such as period of stent placement (1998-2009 vs 2010-2019), prior treatments, peritoneal deposits, and stricture length were evaluated using multivariable Cox regression analysis.Results: A total of 147 patients (62 % male; median age 64 years) were included. After a median of 28 days after stent placement, 82 patients (57 %) had recurrent GOO-symptoms. GOO-symptom free survival was significantly lower in 2010-2019 (P < 0.01). Time period was the only independent predictor for reduced GOO-symptom free survival (HR 1.76, P < 0.01). Stent-related adverse event rates increased over time (1998-2009: 31 % vs 2010-2019: 37 %). Prior treatment with chemotherapy and/or radiotherapy was significantly associated with an increased risk of adverse events (OR 2.53, P = 0.02).Conclusions: Clinical outcome of duodenal stent placement did not improve over time. The decreased GOO-symptom free survival and increased adverse event rate in more recent years are probably related to the chemo- and/or radiotherapy treatment provided prior to duodenal stent placement. [ABSTRACT FROM AUTHOR]

Introduction: There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as current diagnostic imaging techniques, including CT, MRI and PET using FDG, are not fully adequate. The novel PET-tracer "FAPI" has the potential to visualize even small tumour deposits employing the tumour-specific expression of fibroblast-activating protein (FAP) in malignant cells. Methods: We performed a systematic review to select studies investigating the use of FAPI PET for staging pancreatic-, gastric- and cholangiocarcinoma (PROSPERO CRD42022329512). Patient-wise and lesion-wise comparisons were performed for primary tumour (T), lymph nodes (N), organ metastases (M) and peritoneal carcinomatosis (PC). Maximum standardized uptake values (SUVmax) and tumour-to-background ratios (TBR) were compared between PET using FAPI versus FDG (if reported). Results: Ten articles met the inclusion criteria. In all studies, FAPI PET showed superiority over FDG-PET/CT/MRI for the detection of T, N, M and PC, both in the patient-wise and in lesion-wise comparisons (when performed). Additionally, higher SUVmax and TBRmax values were reported for use of FAPI compared to FDG. Conclusions: The positive results of this review warrant prospective clinical studies to investigate the accuracy and clinical value of FAPI PET for diagnosing and staging patients with pancreatic-, gastric- and cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with unresectable perihilar cholangiocarcinoma, adequate biliary drainage is essential. Stent patency remains a challenge in these complex patients, as both plastic and metal stent occlusion may occur, necessitating additional drainage procedures. Radiofrequency ablation (RFA) is a promising local treatment that has already proven its usefulness in other malignancies, such as hepatocellular carcinoma. In this meta-analysis and systematic review, we aimed to compare intraductal RFA with stent placement to stent placement alone in patients with unresectable perihilar cholangiocarcinoma. We found that RFA + stent treatment showed a significantly longer overall survival, in comparison to stent-only treatment. Further research is necessary in order to validate these findings to support the implementation of this promising strategy in clinical practice. Background: One of the cornerstones of palliative treatment for unresectable perihilar cholangiocarcinoma is biliary stent placement in order to restore biliary drainage. In this review, the potential added value of RFA with stent placement in comparison to stent placement alone in patients with unresectable perihilar cholangiocarcinoma is analyzed. Methods: We performed a comprehensive online search for relevant articles in November 2021 (PROSPERO ID: CRD42021288180). The primary endpoint was difference in overall survival. Secondary endpoints included overall survival, stent patency and complications. Only studies comparing survival after RFA + stent placement with stent placement alone were included in the meta-analysis. Non-comparative studies or comparative studies describing stent patency only were included in the systematic review. Results: A total of nine studies, including 217 patients with pCCA who underwent RFA + stent placement and 294 patients who underwent stent-only treatment, met the inclusion criteria for the primary endpoint analysis. Direct comparison between the two treatment groups showed a significantly longer overall survival for RFA + stent treatment, with a pooled HR of 0.65 [95% CI, 0.50–0.84, I2 = 38%]. When all eligible studies were included, RFA + stent treatment revealed an overall survival of 9.5 months [95% CI, 6.3–12.6], whereas survival for stent-only treatment was 7.0 months [95% CI, 5.7–8.2]. Due to the heterogeneity of the data, no pooled data analysis could be performed on stent patency or complications. Conclusions: RFA + stent placement displays promising potential to prolong survival. However, further research incorporating confounding factors like use of palliative chemotherapy is necessary in order to validate these findings. [ABSTRACT FROM AUTHOR]

Background: Perihilar cholangiocarcinoma (pCCA) is a rare tumour that requires complex multidisciplinary management. All known data are almost exclusively derived from expert centres. This study aimed to analyse the outcomes of patients with pCCA in a nationwide cohort. Methods: Data on all patients diagnosed with pCCA in the Netherlands between 2010 and 2018 were obtained from the Netherlands Cancer Registry. Data included type of hospital of diagnosis and the received treatment. Outcomes included the type of treatment and overall survival. Results: A total of 2031 patients were included and the median overall survival for the overall cohort was 5.2 (95% CI 4.7‐5.7) months. Three‐hundred‐ten (15%) patients underwent surgical resection, 271 (13%) underwent palliative systemic treatment, 21 (1%) palliative local anti‐cancer treatment and 1429 (70%) underwent best supportive care. These treatments resulted in a median overall survival of 29.6 (95% CI 25.2‐34.0), 12.2 (95% CI 11.0‐13.3), 14.5 (95%CI 8.2‐20.8) and 2.9 (95% CI 2.6‐3.2) months respectively. Resection rate was 13% in patients who were diagnosed in non‐academic and 32% in academic centres (P <.001), which resulted in a survival difference in favour of academic centres. Median overall survival was 9.7 (95% CI 7.7‐11.7) months in academic centres compared to 4.9 (95% CI 4.3‐5.4) months in non‐academic centres (P <.001). Conclusions: In patients with pCCA, resection rate and overall survival were higher for patients who were diagnosed in academic centres. These results show population‐based outcomes of pCCA and highlight the importance of regional collaboration in the treatment of these patients. [ABSTRACT FROM AUTHOR]

B vitamin deficiencies lead to moderate hyperhomocysteinemia, which has been associated with health and disease. However, concomitant derangements in cellular methylation, reflected by altered plasma S-adenosylmethionine (SAM) or S-adenosylhomocysteine )SAH( concentrations, may be the primary cause. Therefore, we identified determinants of homocysteine, SAM, and SAH concentrations in 336 women, aged 20-48 y, as part of a large study focusing on risk factors for reproductive disorders. Blood was obtained to determine plasma SAM, SAH, and total homocysteine (tHcy), serum vitamin B-12 and folate, RBC folate concentrations, and the related single nucleotide polymorphisms 5,10- methylenetetrahydrofolate reductase (MTHFR) 677C > T and 1 298A> C, methionine synthase reductase (MTRR( 66A> G, and nicotinamide N-methyltransferase IVS1-151G > A. Questionnaires provided information on demographics, lifestyles, and nutrient intakes. Correlation coefficients were calculated and multivariable associations were assessed with a general linear model. Serum folate was positively correlated with SAM concentrations (r = 0.159; P = 0.004). Folate and vitamin B-12 were not correlated with SAH concentrations or the SAM:SAH ratio but were inversely correlated with tHcy concentrations (serum folate r = -0.324: RBC folate r = -0.294; vitamin B-12 r = -0.307; P < 0.01). From the multivariable analysis, BMI was the strongest determinant of SAM (standardized β = 19.145; P < 0.001) and SAH concentrations (standardized β = 3.241; P = 0.010). MTHFR 677TT (standardized β = 0.195; P = 0.001), B vitamin supplement use (standardized β = -0.156; P < 0.001) and dietary protein intake (standardized /3 = -0.011; P < 0.001) were the strongest determinants of tHcy concentrations. Thus, the determinants of SAM and SAH differ from those of tHcy concentrations. Given that BMI was a strong determinant of SAM concentrations, it should be included in future studies on cellular methylation. [ABSTRACT FROM AUTHOR]

The article presents a study investigating the association between the maternal methylation status to the risk of congenital heart diseases (CHD) in the west part of Netherlands. In accordance to the study, it is noted that plasma total homocysteine is significantly dissimilar between the total case group and the nonisolated cases as compared with controls. Based on the data, it is analyzed that the maternal hyperhomocysteinemia is a risk factor for bearing a child with CHD.

Simple Summary: The role of radiotherapy in the treatment of perihilar cholangiocarcinoma has not yet been properly defined. In this prospective study, we therefore explored the addition to first-line chemotherapy of stereotactic body radiation therapy (SBRT) delivered in 15 fractions. Patients eligible for the study had been diagnosed with unresectable perihilar cholangiocarcinoma, and then had no progressive disease after completing treatment with 6–8 cycles of cisplatin-gemcitabine. Primary endpoints were feasibility and safety. Secondary endpoints were local control, progression-free survival, overall survival, and quality of life. As each patient completed the SBRT successfully and no dose-limiting toxicity was found, we consider this treatment to be both feasible and safe. The local control rate and overall survival were promising. However, due to the small sample size of this study, we urge the analysis of this treatment in a larger series of patients. Background: In unresectable pCCA, the standard of care is palliative chemotherapy. We investigated the feasibility and safety of adding stereotactic body radiation therapy (SBRT) after chemotherapy. Methods: Patients with unresectable pCCA, stage T1-T4N0-N1M0, ECOG 0-1, having finished 6–8 cycles of cisplatin and gemcitabine without disease progression were eligible. SBRT was planned in 15 fractions of 3.0–4.5 Gy. The primary endpoints were feasibility (defined as completing SBRT as planned) and toxicity, evaluated within 3 months after SBRT (CTCAE v4.03). A conventional "3 + 3" design was used, corresponding to a sample size of 6 patients. Dose-limiting toxicity (DLT) was defined as grade ≥ 4 hepatobiliary or grade ≥ 3 gastrointestinal toxicity. The secondary endpoints, measured from the start of radiotherapy, were local control, progression-free survival, overall survival, and quality of life (QoL). ClinicalTrials.gov identifier: NCT03307538. Results: Six patients were enrolled between November 2017 and March 2020. SBRT was delivered as planned. All patients were treated with 60Gy (15 × 4.0Gy). No SBRT-related DLT was observed. The most common grade ≥ 3 toxicity was cholangitis (n = 5). The median follow-up was 14 months. The 12-month local control rate was 80%. We observed no substantial changes in QoL. Conclusion: In patients with unresectable pCCA with stable disease after palliative chemotherapy, adding SBRT is feasible and safe. The observed local control merits an additional evaluation of effectiveness. [ABSTRACT FROM AUTHOR]