Imaging differentiation of solid pseudopapillary neoplasms and neuroendocrine neoplasms of the pancreas.

Purpose: The present study aimed to compare the computed tomography (CT) and magnetic resonance imaging (MRI) features of solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine neoplasms (pNENs). Method: Lesion imaging features of 39 patients with SPNs and 127 patients with pNENs were retrospectively extracted from 104 CT and 91 MRI scans. Results: Compared to pNEN patients, SPN patients were significantly younger (mean age 51.8 yrs versus 32.7 yrs) and more often female (female: male ratio, 5.50:1 versus 1.19:1). Most SPNs and pNENs presented as well-defined lesions with an expansive growth pattern. SPNs more often appeared as round or ovoid lesions, compared to pNENs which showed a lobulated or irregular shape in more than half of cases (p<0.01). A surrounding capsule was detected in the majority of SPNs, but only in a minority of pNENs (<0.01). Hemorrhage occurred non-significantly more often in SPNs (p=0.09). Signal inhomogeneity in T1-fat-saturated (p<0.01) and T2-weighted imaging (p=0.046) as well as cystic degeneration (p<0.01) were more often observed in SPNs. Hyperenhancement in the arterial and portal-venous phase was more common in pNENs (p<0.01). Enlargement of locoregional lymph nodes (p<0.01) and liver metastases (p=0.03) were observed in some pNEN patients, but not in SPN patients. Multivariate logistic regression identified the presence of a capsule (p<0.01), absence of arterial hyperenhancement (p<0.01), and low patient age (p<0.01), as independent predictors for SPN. Conclusions: The present study provides three key features for differentiating SPNs from pNENs extracted from a large patient cohort: presence of a capsule, absence of arterial hyperenhancement, and low patient age.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding.

PURPOSE: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors. METHODS: We analyzed PDAC by determining the degree of tumor spiculation on T2-weighted MRI using a 3-tier grading system. The grade of spiculation was correlated with the density of tumor buds quantified in histological sections of the respective surgical specimen according to the guidelines of the International Tumor Budding Consensus Conference (n = 28 patients). RESULTS: 64% of tumors revealed intermediate to high spiculation on MRI. In over 90% of cases, tumor buds were detected. We observed a significant positive rank correlation between the grade of radiological tumor spiculation and the histopathological number of tumor buds (rs = 0.745, p < 0.001). The number of tumor buds was not significantly associated with tumor stage, presence of lymph node metastases, or histopathological grading (p ≥ 0.352). CONCLUSION: Our study identifies a readily available radiological marker for non-invasive estimation of tumor budding, as a correlate for infiltrative tumor growth. This finding could help to identify PDAC patients who might benefit from more extensive peripancreatic soft tissue resection during surgery or stratify patients for personalized therapy concepts.

Comparison between intrauterine application of an antibiotic and an herbal product to treat clinical endometritis in dairy cattle - A randomized multicentre field study.

Uterine diseases are main indications for antibiotic use in dairy cows. To test a non-antibiotic treatment option, we compared the effect of an intrauterine cephapirin (Metricure®; cefapirin benzathin 500 mg per dosis; CEPH) with an intrauterine applied herbal product (25 ml of EucaComp® PlantaVet containing alcoholic extracts of Calendula officinalis L., Mellissa officinalis L., Origanum majorana L. and Eucalyptus globulus Labill. (EUC)) on the clinical cure of endometritis. Examinations of 816 cows between 21 and 35 days after calving were performed and cases of clinical endometritis (n = 169) were included. Diagnosis based on a scoring system for vaginal discharge. Study animals were randomly assigned to one of two treatment groups and treated immediately. After excluding animals with incomplete datasets, 136 cows (EUC: n = 61; CEPH: n = 75) remained for the final analysis. In total, 64% (EUC: 61%, CEPH: 67%) of analysed endometritis cases were considered as clinically cured 14 ± 2 days after the first treatment, 15% stayed uncured after the application of a maximum of two consecutive treatments, leading to an overall clinical cure rate of 85% (EUC: 82%, CEPH: 88%). No statistically difference in clinical cure rates could be observed between both treatment groups nor 14 ± 2 days after the first treatment (p = 0.956) neither regarding the overall cure rate (p = 0.923). In conclusion, the clinical cure of dairy cows' endometritis after the intrauterine application of the herbal product was non-inferior to the intrauterine application of the antibiotic cephapirin. These results could contribute to reduce the antimicrobial use in the daily veterinary routine treatment of endometritis.

Higher conversion rate to knee arthroplasty in female patients following medial open-wedge high tibial osteotomy.

PURPOSE: Most studies about medial open-wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long-term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis. METHODS: The data of three cohorts with long-term outcomes were analysed (n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow-up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender-specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan-Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders. RESULTS: Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower (p = 0.0010). The 5- and 10-year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow-up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p < 0.0001). Females had significantly lower preoperative and postoperative IKDC (p = 0.0438; p = 0.0035) and Lysholm scores (p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders. CONCLUSIONS: Females had higher conversion rates to TKA and lower knee function at the last follow-up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management. LEVEL OF EVIDENCE: Level II.

CT-based screening of sarcopenia and its role in cachexia syndrome in pancreatic cancer.

Since computed tomography (CT) is a part of standard diagnostic protocol in pancreatic ductal adenocarcinoma (PDAC), we have evaluated the value of CT for sarcopenia screening in patients with PDAC, intending to expand the diagnostic value of tomographic studies. In our study, we included 177 patients with available CT images. Two groups were formed: Group 1 consisted of 117 patients with PDAC in various locations and stages and Group 2, or the control group, consisted of 60 "nominally healthy" patients with other somatic non-oncological diseases. The body mass index (BMI) was defined as a ratio of patient's weight to the square of their height (kg/m2). CT-based body composition analysis was performed using commercially available software with evaluation of sarcopenia using skeletal muscle index (SMI, cm2/m2). Based on the SMI values, sarcopenia was found in 67.5% of patients (79 out of 117) in the first patient group. It was found more frequently in males (42 out of 56; 75%) than in females (37 out of 61; 60.6%). Additionally, we observed a decrease in muscle mass (hidden sarcopenia) in 79.7% in patients with a normal BMI. Even in overweight patients, sarcopenia was found in 50% (sarcopenic obesity). In patients with reduced BMI sarcopenia was found in all cases (100%). Statistically significant difference of SMI between two groups was revealed for both sexes (p = 0,0001), with no significant difference between groups in BMI. BMI is an inaccurate value for the assessment of body composition as it does not reflect in the details the human body structure. As SMI may correlate with the prognosis, decreased muscle mass- especially "hidden" sarcopenia or sarcopenic obesity- should be reported. The use of CT-based evaluation of sarcopenia and sarcopenic obesity will allow for a better treatment response assessment in patients with cancer cachexia.

Short-term results of tibial interference screw fixation for transtibial medial meniscus posterior root pull-out repair.

Background: To evaluate the technique of transtibial pull-out repair with tibial interference screw fixation for medial meniscus posterior root (MMPR) tear by reporting on short-term outcomes and complications. Methods: All MMPR repairs performed between January 2019 and August 2021 (n = 70) were retrospectively screened regarding demographic data and surgical parameters. The patients were questioned for performed revision surgery, symptoms and complications. The Numeric Rating Scale (NRS) for pain, Lysholm Knee Score and International Knee Documentation Committee Subjective Knee Form (IKDC) questionnaires were used to evaluate clinical outcome. In cases of revision surgery for re-tear the mode of failure was intraoperatively classified (patients with re-tear were excluded from the clinical follow-up examination). The influence of demographic and treatment parameters (surgical and rehabilitation) on the incidence and mode of re-tear and clinical scores was evaluated. Results: After 2.3 ± 0.7 years, 62 patients (88.6 %) were available for follow-up. There were no direct intra- or postoperative complications. No revision was performed due to symptoms related to the tibial fixation material. The mean surgery time was 33.5 ± 10.8 min. The overall re-tear rate was 17.7 % (11 patients) of whom 10 were treated surgically and one conservatively. Primary mode of failure was suture cut-out from the meniscus (70 %). The NRS, Lysholm Knee Score and subjective IKDC were obtained in 38 patients and improved from 6.8 ± 2.4, 40.1 ± 23.9 and 32.8 ± 16.3 to 2.2 ± 2.2, 80.5 ± 16.3 and 63.0 ± 13.9, respectively (all p < 0.001). No influence was observed from demographic and treatment parameters on re-tear rates or clinical Scores. Conclusions: Tibial interference screw fixation is a fast and promising technique for MMPR transtibial pull-out repair. In the presented technique, utilizing non-absorbable locking sutures alongside tibial interfenrence screw fixation, the primary mode of failure was suture cut-out from the meniscus.

Short-term Outcomes of Robotic Versus Open Pancreatoduodenectomy: Propensity Score-matched Analysis.

OBJECTIVE: The goal of the current study was to investigate the perioperative outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) in a high-volume center. BACKGROUND: Despite RPDs prospective advantages over OPD, current evidence comparing the 2 has been limited and has prompted further investigation. The aim of this study was to compare both approaches while including the learning curve phase for RPD. METHODS: A 1:1 propensity score-matched analysis of a prospective database of RPD with OPD (2017-2022) at a high-volume center was performed. The main outcomes were overall- and pancreas-specific complications. RESULTS: Of 375 patients who underwent PD (OPD n=276; RPD n=99), 180 were included in propensity score-matched analysis (90 per group). RPD was associated with less blood loss [500 (300-800) vs 750 (400-1000) mL; P =0.006] and more patients without a complication (50% vs 19%; P <0.001). Operative time was longer [453 (408-529) vs 306 (247-362) min; P <0.001]; in patients with ductal adenocarcinoma, fewer lymph nodes were harvested [24 (18-27) vs 33 (27-39); P <0.001] with RPD versus OPD. There were no significant differences for major complications (38% vs 47%; P =0.291), reoperation rate (14% vs 10%; P =0.495), postoperative pancreatic fistula (21% vs 23%; P =0.858), and patients with the textbook outcome (62% vs 55%; P =0.452). CONCLUSIONS: Including the learning phase, RPD can be safely implemented in high-volume settings and shows potential for improved perioperative outcomes versus OPD. Pancreas-specific morbidity was unaffected by the robotic approach. Randomized trials with specifically trained pancreatic surgeons and expanded indications for the robotic approach are needed.

Promising Outcomes of Modified ALPPS for Staged Hepatectomy in Cholangiocarcinoma.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage procedure that can potentially cure patients with large cholangiocarcinoma. The current study evaluates the impact of modifications on the outcomes of ALPPS in patients with cholangiocarcinoma. In this single-center study, a series of 30 consecutive patients with cholangiocarcinoma (22 extrahepatic and 8 intrahepatic) who underwent ALPPS between 2011 and 2021 was evaluated. The ALPPS procedure in our center was modified in 2016 by minimizing the first stage of the surgical procedure through biliary externalization after the first stage, antibiotic administration during the interstage phase, and performing biliary reconstructions during the second stage. The rate of postoperative major morbidity and 90-day mortality, as well as the one- and three-year disease-free and overall survival rates were calculated and compared between patients operated before and after 2016. The ALPPS risk score before the second stage of the procedure was lower in patients who were operated on after 2016 (before 2016: median 6.4; after 2016: median 4.4; p = 0.010). Major morbidity decreased from 42.9% before 2016 to 31.3% after 2016, and the 90-day mortality rate decreased from 35.7% before 2016 to 12.5% after 2016. The three-year survival rate increased from 40.8% before 2016 to 73.4% after 2016. Our modified ALPPS procedure improved perioperative and postoperative outcomes in patients with extrahepatic and intrahepatic cholangiocarcinoma. Minimizing the first step of the ALPPS procedure was key to these improvements.

Are T2WI PI-RADS sub-scores of transition zone prostate lesions biased by DWI information? A multi-reader, single-center study.

PURPOSE: According to PI-RADS v2.1, T2-weighted imaging (T2WI) is the dominant sequence for transition zone (TZ) lesions. This study aimed to assess, whether diffusion-weighted imaging (DWI) information influences the assignment of T2WI scores. METHOD: Out of 283 prostate MRI examinations with correlated biopsy results, fourty-four patients were selected retrospectively: first, 22 patients with a TZ lesion with T2WI and DWI scores ≥ 4, to represent lesions with unequivocal suspicion on T2WI and DWI. Second, 22 additional patients with TZ lesions of similar T2WI appearance but with corresponding DWI score ≤ 3 were added as control. Four residents and one board-certified radiologist each performed two assessments of the included patients: First, only T2WI was available (T2-only read); second, both T2WI and DWI sequences were available (biparametric read). Lesion scores were assessed using Wilcoxon signed-rank test, inter-reader agreement using weighted kappa and Kendall's W statistics, and sensitivity/specificity using McNemar test. RESULTS: The T2WI scores were significantly different between the T2-only and biparametric read for 3 out of 4 residents (p ≤ 0.049) but not for the radiologist. The overall PI-RADS scores derived from the two reading sessions differed considerably for 35/220 cases (all readers pooled). Inter-reader agreement was fair for the T2WI and overall PI-RADS scores (mean kappa 0.27-0.30) and moderate for the DWI scores (mean kappa 0.43). CONCLUSIONS: For inexperienced readers, assessment of T2WI is variable and potentially biased by availability of DWI information, which can lead to changes of overall PI-RADS score and consequently clinical management. Assessment of T2WI should be performed before reviewing DWI to ensure non-biased interpretation of TZ lesions in the dominant sequence.

Pancreatic CT perfusion: quantitative meta-analysis of disease discrimination, protocol development, and effect of CT parameters.

BACKGROUND: This study provides a quantitative meta-analysis of pancreatic CT perfusion studies, investigating choice of study parameters, ability for quantitative discrimination of pancreatic diseases, and influence of acquisition and reconstruction parameters on reported results. METHODS: Based on a PubMed search with key terms 'pancreas' or 'pancreatic,' 'dynamic' or 'perfusion,' and 'computed tomography' or 'CT,' 491 articles published between 1982 and 2020 were screened for inclusion in the study. Inclusion criteria were: reported original data, human subjects, five or more datasets, measurements of pancreas or pancreatic pathologies, and reported quantitative perfusion parameters. Study parameters and reported quantitative measurements were extracted, and heterogeneity of study parameters and trends over time are analyzed. Pooled data were tested with weighted ANOVA and ANCOVA models for differences in perfusion results between normal pancreas, pancreatitis, PDAC (pancreatic ductal adenocarcinoma), and non-PDAC (e.g., neuroendocrine tumors, insulinomas) and based on study parameters. RESULTS: Reported acquisition parameters were heterogeneous, except for contrast agent amount and injection rate. Tube potential and slice thickness decreased, whereas tube current time product and scan coverage increased over time. Blood flow and blood volume showed significant differences between pathologies (both p < 0.001), unlike permeability (p = 0.11). Study parameters showed a significant effect on reported quantitative measurements (p < 0.05). CONCLUSIONS: Significant differences in perfusion measurements between pathologies could be shown for pooled data despite observed heterogeneity in study parameters. Statistical analysis indicates most influential parameters for future optimization and standardization of acquisition protocols. CRITICAL RELEVANCE STATEMENT: Quantitative CT perfusion enables differentiation of pancreatic pathologies despite the heterogeneity of study parameters in current clinical practice.

Evaluation and timing optimization of CT perfusion first pass analysis in comparison to maximum slope model in pancreatic adenocarcinoma.

For implementation, performance evaluation and timing optimization of CT perfusion first pass analysis (FPA) by correlation with maximum slope model (MSM) in pancreatic adenocarcinoma, dynamic CT perfusion acquisitions of 34 time-points were performed in 16 pancreatic adenocarcinoma patients. Regions of interest were marked in both parenchyma and carcinoma. FPA, a low radiation exposure CT perfusion technique, was implemented. Blood flow (BF) perfusion maps were calculated using FPA and MSM. Pearson's correlation between FPA and MSM was calculated at each evaluated time-point to determine optimum timing for FPA. Differences in BF between parenchyma and carcinoma were calculated. Average BF for MSM was 106.8 ± 41.5 ml/100 ml/min in parenchyma and 42.0 ± 24.8 ml/100 ml/min in carcinoma, respectively. For FPA, values ranged from 85.6 ± 37.5 ml/100 ml/min to 117.7 ± 44.5 ml/100 ml/min in parenchyma and from 27.3 ± 18.8 ml/100 ml/min to 39.5 ± 26.6 ml/100 ml/min in carcinoma, depending on acquisition timing. A significant difference (p value < 0.0001) between carcinoma and parenchyma was observed at all acquisition times based on FPA measurements. FPA shows high correlation with MSM (r > 0.90) and 94% reduction in the radiation dose compared to MSM. CT perfusion FPA, where the first scan is obtained after the arterial input function exceeds a threshold of 120 HU, followed by a second scan after 15.5-20.0 s, could be used as a potential imaging biomarker with low radiation exposure for diagnosing and evaluating pancreatic carcinoma in clinical practice, showing high correlation with MSM and the ability to differentiate between parenchyma and carcinoma.

Surgery for intraductal papillary mucinous neoplasms in young patients: High-risk population.

BACKGROUND: Intraductal papillary mucinous neoplasms of the pancreas are uncommon in young individuals. Management of these patients is challenging because the risk of malignancy and recurrence after surgery remains unclear. The aim of the present study was to assess the long-term risk for intraductal papillary mucinous neoplasm recurrence after surgery for intraductal papillary mucinous neoplasms in patients ≤50 years of age. METHODS: Perioperative and long-term follow-up data of patients who had undergone surgery for intraductal papillary mucinous neoplasms between 2004 and 2020 were extracted from a prospective unicentric database and retrospectively analyzed. RESULTS: Seventy-eight patients underwent surgical treatment for benign intraductal papillary mucinous neoplasms (low-grade n = 22 and intermediate-grade n = 21) and malignant intraductal papillary mucinous neoplasms (high-grade n = 16 and intraductal papillary mucinous neoplasm-associated carcinoma n = 19). Severe postoperative morbidity (Clavien-Dindo ≥III) was found in 14 patients (18%). The median length of hospital stay was 10 days. No perioperative mortality was observed. The median length of follow-up was 72 months. Recurrence of intraductal papillary mucinous neoplasm-associated carcinoma was found in 6 patients (19%) with malignant intraductal papillary mucinous neoplasm and 1 patient (3%) with benign intraductal papillary mucinous neoplasm. CONCLUSION: Surgery for intraductal papillary mucinous neoplasm is safe and can be performed with low morbidity and potentially no mortality in young patients. Given the high rate of malignancy (45%), these patients with intraductal papillary mucinous neoplasms represent a high-risk population, and prophylactic surgical treatment should be considered in these patients with long life expectancies. Regular clinical and radiologic follow-up examinations are important to rule out disease recurrence, which is high, especially in patients with intraductal papillary mucinous neoplasm-associated carcinoma.

Evaluation of optimal acquisition delays of DECT iodine maps in pancreatic adenocarcinoma: A potential alternative to the Patlak model of CT perfusion.

Introduction: By using bolus tracking with an appropriate acquisition delay dual-energy computed tomography (DECT) iodine maps might serve as a replacement of CT perfusion maps at reduced radiation exposure. This study aimed to evaluate the optimal acquisition delays of DECT for the replacement of parameter maps calculated with the Patlak model in pancreatic adenocarcinoma by corresponding iodine maps. Materials and methods: Dual-source dynamic DECT acquisitions at 80 kVp/Sn140 kVp of 14 patients with pancreatic carcinoma were used to calculate CT perfusion maps of blood volume and permeability with the Patlak model. DECT iodine maps were generated from individual DECT acquisitions, matching acquisition times relative to prior bolus-triggered three-phase CT acquisitions for investigating different acquisition delays. Correlation between perfusion parameters and iodine concentrations was determined for acquisition delays between -6 s and 33 s. Results: Correlation between iodine concentrations and perfusion parameters ranged from -0.05 to 0.63 for blood volume and from -0.05 to 0.71 for permeability, depending on potential trigger delay. The correlation was significant for potential acquisition delays above 1.5 s for blood volume and above 9.0 s for permeability (both p < 0.05). Maximum correlation occurred at an acquisition delay of 15.0 s for blood volume (r = 0.63) and at 25.5 s for permeability (r = 0.71), with significantly lower iodine concentrations in carcinoma (15.0 s: 1.3 ± 0.5 mg/ml; 22.5 s: 1.4 ± 0.7 mg/ml) than in non-neoplastic pancreatic parenchyma (15.0 s: 2.3 ± 0.8 mg/ml; 22.5 s: 2.4 ± 0.6 mg/ml; p < 0.05). Discussion: In the future, well-timed DECT iodine maps acquired with bolus tracking could provide an alternative to permeability and blood volume maps calculated with the Patlak model.

Lymphoepithelial cyst of the pancreas: can common imaging features help to avoid resection?

BACKGROUND: Differentiation of cystic pancreatic neoplasms remains a challenging task for radiologists regarding the main aim of identifying malignant and premalignant lesions. PURPOSE: The study aimed to compare the radiological features of lymphoepithelial cysts (LEC) with other cystic pancreatic lesions, which could help to differentiate them in order to avoid unnecessary resection. MATERIAL AND METHODS: We retrospectively reviewed 10 cases of resected and histopathologically confirmed LECs during a 12-year period with available imaging studies; 20 patients with mucinous cystic neoplasms (MCN), 20 patients with branch-duct intraductal papillary mucinous neoplasms (BD-IPMN), and 20 patients with serous cystic neoplasms (SCN) were selected to serve as control groups. Imaging findings as well as clinical data were analyzed. RESULTS: The following imaging morphology of LEC was identified: simple cystic appearance (20%) and mixed cystic-solid appearance (80%) with either a diffuse subsolid component (30%) or mural nodule(s) (50%). All lesions revealed exophytic location with a strong male predominance (9:1). MCNs occurred exclusively in middle-aged women, IPMN in both sexes showed slight male predominance (13:7), and SCN showed female predominance (5:15). Median patient age in LEC (48.5, IQR 47-54.5) was significantly younger compared to IPMN (p < 0.001) and SCN (p = 0.02). Unenhanced CT attenuation of LEC was higher than MCNs (p = 0.025) and IPMNs (p = 0.021), showing no significant difference to SCN (p = 0.343). CONCLUSION: The present study provides key radiological features of LEC for the differentiation from other cystic pancreatic lesions such as increased CT attenuation in the unenhanced phase, absence of a connection to the main pancreatic duct (MPD), and exophytic location. In addition to these imaging features, clinical data, such as male predominance in LEC, must be considered for the differentiation of cystic pancreatic lesions.

IL-17A-producing CD8+ T cells promote PDAC via induction of inflammatory cancer-associated fibroblasts.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is characterised by an abundant desmoplastic stroma composed of cancer-associated fibroblasts (CAF) and interspersed immune cells. A non-canonical CD8+ T-cell subpopulation producing IL-17A (Tc17) promotes autoimmunity and has been identified in tumours. Here, we evaluated the Tc17 role in PDAC. DESIGN: Infiltration of Tc17 cells in PDAC tissue was correlated with patient overall survival and tumour stage. Wild-type (WT) or Il17ra-/- quiescent pancreatic stellate cells (qPSC) were exposed to conditional media obtained from Tc17 cells (Tc17-CM); moreover, co-culture of Tc17-CM-induced inflammatory (i)CAF (Tc17-iCAF) with tumour cells was performed. IL-17A/F-, IL-17RA-, RAG1-deficient and Foxn1nu/nu mice were used to study the Tc17 role in subcutaneous and orthotopic PDAC mouse models. RESULTS: Increased abundance of Tc17 cells highly correlated with reduced survival and advanced tumour stage in PDAC. Tc17-CM induced iCAF differentiation as assessed by the expression of iCAF-associated genes via synergism of IL-17A and TNF. Accordingly, IL-17RA controlled the responsiveness of qPSC to Tc17-CM. Pancreatic tumour cells co-cultured with Tc17-iCAF displayed enhanced proliferation and increased expression of genes implicated in proliferation, metabolism and protection from apoptosis. Tc17-iCAF accelerated growth of mouse and human tumours in Rag1-/- and Foxn1nu/nu mice, respectively. Finally, Il17ra-expressed by fibroblasts was required for Tc17-driven tumour growth in vivo. CONCLUSIONS: We identified Tc17 as a novel protumourigenic CD8+ T-cell subtype in PDAC, which accelerated tumour growth via IL-17RA-dependent stroma modification. We described a crosstalk between three cell types, Tc17, fibroblasts and tumour cells, promoting PDAC progression, which resulted in poor prognosis for patients.

High prevalence of increased posterior tibial slope in ACL revision surgery demands a patient-specific approach.

PURPOSE: To determine the prevalence of an "increased posterior tibial slope (PTS)" (PTS ≥ 12°) in a population with one, two or ≥ three anterior cruciate ligament (ACL) graft insufficiencies. Furthermore, to investigate whether the prevalence of an increased PTS and the absolute PTS increases with an increasing number of ACL graft insufficiencies, as well as to determine the survival time of the first ACL graft. METHODS: Patients diagnosed with an ACL graft insufficiency between January 2021 and March 2022 were included. The PTS was measured using the proximal anatomical tibial axis on long lateral knee radiographs. Patients were divided into 3 groups depending on the number of ACL graft insufficiencies: group A (1 graft insufficiency), group B (2 graft insufficiencies) and group C (≥ 3 graft insufficiencies). The prevalence of increased PTS and absolute PTS between groups was compared alongside the survival of the first ACL graft between patients with or without increased PTS. RESULTS: Two-hundred and six patients (147 males/59 females) met the inclusion criteria. 73 patients showed an increased PTS [prevalence 35% [95% confidence interval (CI) (29%; 42%)]. 155 patients were found in category A, 42 patients in B and 9 patients in C. The prevalence of increased PTS for group A, B and C was, 32% [95% CI (25%; 40%)], 38% [95% CI (23%; 53%)] and 78% [95% CI (51%; 100%)], respectively. The prevalence of increased PTS and mean PTS did not increase significantly between group A and B. However, both parameters increased significantly between group A and C, and group B and C (p < 0.05). The survival time of the first ACL graft in patients with or without an increased PTS was 3 (interquartile range (IQR) 5) and 6 years (IQR 9), respectively (p < 0.05). CONCLUSION: There is a 35% prevalence of increased PTS in the studied ACL graft insufficient patient cohort. The survival of the first ACL graft is shorter in patients with an increased PTS. Surgeons should be aware of the high prevalence of increased PTS when consulting patients for revision ACL reconstruction as it is an important risk factor for recurrent instability.

Celiac Axis Stenosis is an Underestimated Risk Factor for Increased Morbidity After Pancreatoduodenectomy.

OBJECTIVE: To assesses the prevalence and severity of CAS in patients undergoing PD/total pancreatectomy and its association with major postoperative complications after PD. SUMMARY OF BACKGROUND DATA: CAS may increase the risk of ischemic complications after PD. However, the prevalence of CAS and its relevance to major morbidity remain unknown. METHODS: All patients with a preoperative computed tomography with arterial phase undergoing partial PD or TP between 2014 and 2017 were identified from a prospective database. CAS was assessed based on computed tomography and graded according to its severity: no stenosis (<30%), grade A (30%-<50%), grade B (50%-≤80%), and grade C (>80%). Postoperative complications were assessed and uni- and multivariable risk analyses were performed. RESULTS: Of 989 patients, 273 (27.5%) had CAS: 177 (17.9%) with grade A, 83 (8.4%) with grade B, and 13 (1.3%) with grade C. Postoperative morbidity and 90-day mortality occurred in 278 (28.1%) patients and 41 (4.1%) patients, respectively. CAS was associated with clinically relevant pancreatic fistula ( P =0.019), liver perfusion failure ( P =0.003), gastric ischemia ( P =0.001), clinically relevant biliary leakage ( P =0.006), and intensive care unit ( P =0.016) and hospital stay ( P =0.001). Multivariable analyses confirmed grade B and C CAS as independent risk factors for liver perfusion failure; in addition, grade C CAS was an independent risk factor for clinically relevant pancreatic fistula and gastric complications. CONCLUSIONS: CAS is common in patients undergoing PD. Higher grade of CAS is associated with an increased risk for clinically relevant complications, including liver perfusion failure and postoperative pancreatic fistula. Precise radiological assessment may help to identify CAS. Future studies should investigate measures to mitigate CAS-associated risks.

Double level osteotomy for medial osteoarthritis and bifocal varus malalignment has excellent short-term results while maintaining physiologic radiographic joint parameters.

PURPOSE: The purpose of this study was to prospectively evaluate the clinical and radiological results of double level osteotomy (distal femoral lateral closed wedge and proximal tibial medial open wedge) in medial osteoarthritis and varus malalignment due to bifocal deformity of femur and tibia. METHODS: From 2017 to 2019 all cases of DLO in osteoarthritic varus malaligned knees with bifocal deformity (femoral and tibial deformity) were prospectively enrolled into this observational therapeutic study. Evaluation was performed preoperatively, at six, twelve, 18 and 24 months with regard to survival (not requiring arthroplasty), functional outcome [subjective International Knee Documentation Committee score (IKDC), Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome score (KOOS) and Tegner Activity Scale], pain level (numeric rating scale), subjective satisfaction (rating 1-5), radiographic parameters on a pre-and postoperative full leg x-rays (mechanical axis, mechanical proximal tibial and distal femoral angles) and complications. For statistical evaluation student's t test, Mann-Whitney U test and Wilcoxon-signed-rank test were used. RESULTS: Fifty-two consecutive cases in 48 patients were enrolled in the study. Three cases were excluded, resulting in a follow-up rate of 94%. No arthroplasties were performed within follow-up. All functional outcome scores substantially and significantly increased as early as six months after the index procedure and further increased until final follow-up (p < 0.001). Pain level significantly decreased (p < 0.001). At final follow-up all patients stated that they would retrospectively undergo the operation again, and rated the result with 4.5 ± 0.6 out of 5 (3-5). Radiographic parameters were within physiological limits postoperatively. No severe complications occurred. CONCLUSIONS: Double level osteotomy has excellent short-term results while maintaining physiological radiographic parameters. Therefore, it should be an integral part and standard procedure in realignment surgery for monocompartimental osteoarthritis. LEVEL OF EVIDENCE: IV (prospective observational therapeutic study).

Low bone mineral density is a prognostic factor for elderly patients with HCC undergoing TACE: results from a multicenter study.

OBJECTIVES: Low bone mineral density (BMD) was recently identified as a novel risk factor for patients with hepatocellular carcinoma (HCC). In this multicenter study, we aimed to validate the role of BMD as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: This retrospective multicenter trial included 908 treatment-naïve patients with HCC who were undergoing TACE as a first-line treatment, at six tertiary care centers, between 2010 and 2020. BMD was assessed by measuring the mean Hounsfield units (HUs) in the midvertebral core of the 11th thoracic vertebra, on contrast-enhanced computer tomography performed before treatment. We assessed the influence of BMD on median overall survival (OS) and performed multivariate analysis including established estimates for survival. RESULTS: The median BMD was 145 HU (IQR, 115-175 HU). Patients with a high BMD (≥ 114 HU) had a median OS of 22.2 months, while patients with a low BMD (< 114 HU) had a lower median OS of only 16.2 months (p < .001). Besides albumin, bilirubin, tumor number, and tumor diameter, BMD remained an independent prognostic factor in multivariate analysis. CONCLUSIONS: BMD is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. The integration of BMD into novel scoring systems could potentially improve survival prediction and clinical decision-making. KEY POINTS: • Bone mineral density can be easily assessed in routinely acquired pre-interventional computed tomography scans. • Bone mineral density is an independent predictive factor for survival in elderly patients with HCC undergoing TACE. • Thus, bone mineral density is a novel imaging biomarker for prognosis prediction in elderly patients with HCC undergoing TACE.

Generating evidence for diagnosis and therapy of RarE LIVEr disease: the RELIVE Initiative for systematic reviews and meta-analyses.

BACKGROUND: Rare liver lesions and diseases have seldomly aroused major interest of researchers. For most guidelines, presumably similar clinical conditions are pooled without detailed investigations of singularities that they present. MAIN TEXT: A multidisciplinary project aiming to establish evidence-based therapies for rare liver diseases has been founded. A series of systematic reviews and meta-analyses will be the starting point for a structured development of guidelines for rare conditions of the liver affecting pediatric and adult populations. The novel approach will be focusing on case reports and small patient series with distinct rare liver diseases without pooling several presumably acceptably similar conditions. Thus, a vital resource of information will be utilized, which has been largely neglected hitherto. CONCLUSION: Highly specific recommendations based on highest available evidence will therefore be developed for specific conditions, advancing the individualized medicine approach for the afflicted patients.