Preoperative MRI radiomic analysis for predicting local tumor progression in colorectal liver metastases before microwave ablation.

PURPOSE: Radiomics may aid in predicting prognosis in patients with colorectal liver metastases (CLM). Consistent data is available on CT, yet limited data is available on MRI. This study assesses the capability of MRI-derived radiomic features (RFs) to predict local tumor progression-free survival (LTPFS) in patients with CLMs treated with microwave ablation (MWA). METHODS: All CLM patients with pre-operative Gadoxetic acid-MRI treated with MWA in a single institution between September 2015 and February 2022 were evaluated. Pre-procedural information was retrieved retrospectively. Two observers manually segmented CLMs on T2 and T1-Hepatobiliary phase (T1-HBP) scans. After inter-observer variability testing, 148/182 RFs showed robustness on T1-HBP, and 141/182 on T2 (ICC > 0.7).Cox multivariate analysis was run to establish clinical (CLIN-mod), radiomic (RAD-T1, RAD-T2), and combined (COMB-T1, COMB-T2) models for LTPFS prediction. RESULTS: Seventy-six CLMs (43 patients) were assessed. Median follow-up was 14 months. LTP occurred in 19 lesions (25%).CLIN-mod was composed of minimal ablation margins (MAMs), intra-segment progression and primary tumor grade and exhibited moderately high discriminatory power in predicting LTPFS (AUC = 0.89, p = 0.0001). Both RAD-T1 and RAD-T2 were able to predict LTPFS: (RAD-T1: AUC = 0.83, p = 0.0003; RAD-T2: AUC = 0.79, p = 0.001). Combined models yielded the strongest performance (COMB-T1: AUC = 0.98, p = 0.0001; COMB-T2: AUC = 0.95, p = 0.0003). Both combined models included MAMs and tumor regression grade; COMB-T1 also featured 10th percentile of signal intensity, while tumor flatness was present in COMB-T2. CONCLUSION: MRI-based radiomic evaluation of CLMs is feasible and potentially useful for LTP prediction. Combined models outperformed clinical or radiomic models alone for LTPFS prediction.

Proliferative features of IgG4-related disease.

IgG4-related disease is an immune-mediated disease that can lead to substantial morbidity and organ damage. Capable of affecting nearly any organ system or anatomic site, and showing considerable overlap in clinical presentation with various other diseases, IgG4-related disease often poses a diagnostic challenge for clinicians. Furthermore, there are no diagnostic biomarkers with high specificity for IgG4-related disease, and histopathological examination is nuanced and requires clinical correlation for accurate diagnosis. Therefore, it is crucial for clinicians to recognise the clinical phenotypes of IgG4-related disease. The disease is generally considered to have predominantly fibrotic and proliferative (or inflammatory) manifestations, with distinct clinical, serological and histopathological findings associated with each manifestation. However, the fibrotic and proliferative manifestations of this disease frequently occur together, thereby blurring this dichotomous distinction. In this Series paper, we provide a detailed overview of the clinical manifestations typical of the proliferative features of IgG4-related disease, with an emphasis on the diagnostic evaluation and differential diagnosis of each proliferative disease manifestation. In addition, we summarise the immune mechanisms underlying IgG4-related disease, suggest a framework for how to approach management and monitoring after the diagnosis is established, and highlight current unmet needs for patient care surrounding this disease.

Very Early Recurrence After Curative Resection for Pancreatic Ductal Adenocarcinoma: Proof of Concept for a "Biological R2 Definition".

PURPOSE: Very early recurrence after radical surgery for pancreatic ductal adenocarcinoma (PDAC) has been poorly investigated. This study was designed to evaluate this group of patients who developed recurrence, within 12 weeks after surgery, defined as "biological R2 resections (bR2)." METHODS: Data from patients who underwent surgical resection as upfront procedure or after neoadjuvant treatment for PDAC between 2015 and 2019 were analyzed. Disease-free, disease-specific survival, and independent predictors of early recurrence were examined. The same analysis was performed separately for upfront and neoadjuvant treated patients. RESULTS: Of the 573 patients included in the study, 63 (11%) were classified as bR2. The rate of neoadjuvant treatment was similar in bR2 and in the remaining patients (44 vs. 42%, p = 0.78). After a median follow-up of 27 months, median DFS and DSS for the entire cohort were 17 and 43 months, respectively. Median DSS of bR2 group was 13 months. The only preoperative identifiable independent predictor of very early recurrence was body-tail site lesion, whereas all other were pathological: higher pT (8th classification), G3 differentiation, and high lymph node ratio. These predictors were confirmed for patients undergoing upfront surgery, whereas in the neoadjuvant group the only independent predictor was pT. CONCLUSIONS: One of ten patients with "radical" resected PDAC relapses very early after surgery (bR2); hence, imaging must be routinely repeated within 12 weeks. Despite higher biological aggressiveness and worse pathology, this bR2 cluster eludes our preoperative examinations.

Association of autoimmune pancreatitis and intraductal papillary mucinous neoplasm. A retrospective analysis from a tertiary care referral center.

BACKGROUND: Autoimmune Pancreatitis (AIP) is a rare chronic inflammatory disease affecting the pancreas. Chronic pancreatic inflammation represents a risk factor for pre-neoplastic conditions such as Intraductal Papillary Mucinous Neoplasia (IPMN). Due to the rarity of AIP, the incidence, and clinical features of IPMN occurring in AIP patients remains unknown. AIMS: In the present study we aimed to explore the relationship between AIP and IPMN and to characterize the clinical features and outcomes of IPMN occurring in the context of AIP. METHODS: We retrospectively (2008-2020) analyzed the clinical and radiological records of a large single center cohort of patients with AIP and investigated the prevalence of IPMN. We then compared the clinical, laboratory and radiological characteristics of patients with IPMN and AIP with a cohort of patients with isolated IPMN. RESULTS: Five hundred and nineteen patients were included in this retrospective study. Sixteen patients had concomitant IPMN and AIP(3%); 61 patients had isolated AIP (12%); 442 patients had isolated IPMN (85%). The prevalence of IPMN in patients with AIP was higher than that observed in the general population (21%vs8-10%). Worrisome Features and High-Risk Stigmata were more frequently observed in IPMN occurring together with AIP compared to isolated IPMN(p < 0.05). Based on radiological features IPMN in the context of AIP was more frequently of main-duct type compared to isolated IPMN(p < 0.05). CONCLUSION: Our data suggest that AIP represents a chronic inflammatory condition that might favor IPMN development with high-risk features. Prolonged surveillance of these patients and longitudinal studies are required to further test the association with AIP and malignant and pre-malignant conditions.

Macklin Effect: From Pathophysiology to Clinical Implication.

Air leak syndromes (such as pneumomediastinum, pneumothorax, or subcutaneous emphysema) are frequent complications of acute respiratory distress syndrome (ARDS). Unfortunately, the development of air leaks is associated with worse outcomes. In addition, it has been hypothesized that the development of pneumomediastinum could be a marker of disease severity in patients with respiratory failure receiving noninvasive respiratory support or assisted ventilation. The so-called Macklin effect (or pulmonary interstitial emphysema) is the air dissection of the lung bronchovascular tree from peripheral to central airways following injury to distal alveoli. Ultimately, the progression of the Macklin effect leads to the development of pneumomediastinum, subcutaneous emphysema, or pneumothorax. The Macklin effect is identifiable on a chest computed tomography (CT) scan. The Macklin effect could be an accurate predictor of barotrauma in patients with ARDS (sensitivity = 89.2% [95% CI: 74.6-96.9]; specificity = 95.6% [95% CI: 90.6-98.4]), and may be a marker of disease severity. Accordingly, the detection of the Macklin effect on a chest CT scan could be used to select which patients with ARDS might benefit from different treatment algorithms, including advanced respiratory monitoring, early intubation, or, potentially, the institution of early extracorporeal support with or without invasive ventilation. In this video, the authors summarize the pathophysiology and potential clinical significance and applications of the Macklin effect in patients with acute respiratory failure.

Exploring the optimal therapeutic management of stage ypIA pancreatic ductal adenocarcinoma patients in the era of primary chemotherapy.

BACKGROUND: Data on the proper post-surgical chemotherapy (PSC) in pancreatic ductal adenocarcinoma (PDAC) patients already treated with neoadjuvant therapy (NAT) are lacking, especially for stage ypIA. AIM AND METHODS: We retrospectively analyzed ypT1N0M0 (ypIA) PDAC patients resected after NAT between 2015 and 2020 at our Institution. Primary endpoint was median disease free-survival (DFS) according to PSC treatment. RESULTS: Seventy-five out of 363 patients achieved a pathological ypIA after NAT (20.6%) and 72 were analyzed. Among the study population 34 patients (47%) were treated with NAT ≤4 months and 38 (53%) >4 months. After surgery, 10 patients (14%) received PSC using the same multidrug NAT regimen (Group A); 35 (49%) received PSC with a different regimen (Group B), with either single agents in 24 patients (68.5%) or combination schedules in 11 (31.5%); 27 patients (14%) did not receive any PSC (Group C). DFS was longer in group A and C as opposed to group B (p = 0.006). CONCLUSION: Patients affected by ypIA PDAC treated with a proper multi-agent chemotherapy for more than 4 months show an improved DFS, regardless of the peri­operative or totally pre-surgical administration of treatment.

Single-Center Retrospective Study Comparing Double Vein Embolization via a Trans-Jugular Approach with Liver Venous Deprivation via a Trans-Hepatic Approach.

PURPOSE: To compare safety, technical and clinical outcomes of double vein embolization (DVE) via a trans-jugular approach with liver venous deprivation (LVD) via a trans-hepatic approach. MATERIALS AND METHODS: A single-center retrospective analysis was conducted on patients undergoing simultaneous portal and hepatic veins embolization in view of a major hepatectomy (June 2019-November 2022). Hepatic vein embolization was performed either by transjugular plug (DVE) or by transhepatic plug followed by glue injection (LVD). Inclusion criteria were availability of pre-procedural CT scan, and availability of CT scans acquired 10 days and 25 days post-procedure. Comparative data included complication rate, fluoroscopy time, dose area product (DAP), Future Liver Remnant volume and function increase (FLR-V and FLR-F increase, respectively) and clinical outcomes. RESULTS: Thirty-six patients (n = 14 DVE; n = 22 LVD) were included. No baseline significant differences were observed among the two groups. One grade-3 complication (2.8%) was observed in the LVD group; one case of technical failure (2.8%) was observed in the DVE group. Fluoroscopy time and DAP were similar between DVE and LVD (29 ± 17.7 vs. 25 ± 8.2 min, p = 0.97; 105.1 ± 63.5 vs. 143.4 ± 79.5 Gy·cm2, p = 0.15). No differences arose at either time-point in FLR-V increase (46.7 ± 23.1% vs. 48.2 ± 28.2%, 52.9 ± 30.9% vs. 53.2 ± 29%, respectively, p = 0.9). FLR-F increase also did not differ significantly (62.8 ± 55.2 vs. 67.4 ± 57.5, p = 0.9). No differences in drop-out rate from surgery were observed. (28.6% vs. 27.3%, p = 0.93). One case of grade-B post-hepatectomy liver failure (2.8%) was observed in the LVD group. CONCLUSION: LVD via transhepatic approach and DVE via transjugular approach seem equally safe and effective. Level of Evidence Level 3, Retrospective Cohort Study.

Feasibility, safety and efficacy of COVID-19 severe acute respiratory distress syndrome management without invasive mechanical ventilation.

BACKGROUND: COVID-19 acute respiratory distress syndrome (ARDS) is often managed with mechanical ventilation (MV), requiring sedation and paralysis, with associated risk of complications. There is limited evidence on the use of high flow nasal cannula (HFNC). We hypothesized that management of COVID-19 ARDS without MV is feasible. METHODS: Included were all adult patients diagnosed with COVID-19 ARDS, with PaO2/FiO2 ratio <100 at admission, and whose management was initially performed without MV. We evaluated need for intubation during ICU stay, mortality and hospital/ICU length of stay (LOS). RESULTS: Out of 118 patients, 41 were managed only with HFNC from hospital admission (and at least during first 24 hours in ICU) and had a PaO2/FiO2 ratio <100 (72.9±13.0). Twenty-nine out of 41 patients never required MV: 24 of them survived and were discharged home. Their median ICU LOS was 11 (7-17) days, and their hospital LOS was 29 (18-45) days. We identified PaO2/FiO2 ratio at ICU admission as the only significant predictor for need for MV during ICU stay. We also identified age, length of non-invasive respiratory support before ICU admission, mean value of PaO2/FiO2 ratio during first half and whole ICU stay as predictors of mortality. CONCLUSIONS: It is safe to monitor in ICU and use HFNC in patients affected by COVID-19 ARDS who initially present data suggesting an early need for intubation. The 41 patients admitted with a PaO2/FiO2 ratio <100 and initially treated only with HFNC show a 22% mortality that is in the lower range of what is reported in recent literature.

Barotrauma during Noninvasive Respiratory Support in COVID-19 Pneumonia Outside ICU: The Ancillary COVIMIX-2 Study.

BACKGROUND: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting. METHODS: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded. RESULTS: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls (p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO2/FiO2 (p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001). CONCLUSIONS: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Limited impact of discretization/interpolation parameters on the predictive power of CT radiomic features in a surgical cohort of pancreatic cancer patients.

PURPOSE: To explore the variation of the discriminative power of CT (Computed Tomography) radiomic features (RF) against image discretization/interpolation in predicting early distant relapses (EDR) after upfront surgery. MATERIALS AND METHODS: Data of 144 patients with pre-surgical high contrast CT were processed consistently with IBSI (Image Biomarker Standardization Initiative) guidelines. Image interpolation/discretization parameters were intentionally changed, including cubic voxel size (0.21-27 mm3) and binning (32-128 grey levels) in a 15 parameter's sets. After excluding RF with poor inter-observer delineation agreement (ICC < 0.80) and not negligible inter-scanner variability, the variation of 80 RF against discretization/interpolation was first quantified. Then, their ability in classifying patients with early distant relapses (EDR, < 10 months, previously assessed at the first quartile value of time-to-relapse) was investigated in terms of AUC (Area Under Curve) variation for those RF significantly associated to EDR. RESULTS: Despite RF variability against discretization/interpolation parameters was large and only 30/80 RF showed %COV < 20 (%COV = 100*STDEV/MEAN), AUC changes were relatively limited: for 30 RF significantly associated with EDR (AUC values around 0.60-0.70), the mean values of SD of AUC variability and AUC range were 0.02 and 0.05 respectively. AUC ranges were between 0.00 and 0.11, with values ≤ 0.05 in 16/30 RF. These variations were further reduced when excluding the extreme values of 32 and 128 for grey levels (Average AUC range 0.04, with values between 0.00 and 0.08). CONCLUSIONS: The discriminative power of CT RF in the prediction of EDR after upfront surgery for pancreatic cancer is relatively invariant against image interpolation/discretization within a large range of voxel sizes and binning.

Two-year multidisciplinary follow-up of COVID-19 patients requiring invasive and noninvasive respiratory support.

BACKGROUND: COVID-19 patients frequently develop respiratory failure requiring mechanical ventilation. Data on long-term survival of patients who had severe COVID-19 are insufficient. We assessed and compared two-year survival, CT imaging, quality of life, and functional recovery of COVID-19 ARDS patients requiring respiratory support with invasive (IMV) versus noninvasive ventilation (NIV). METHODS: Patients with COVID-19 pneumonia admitted up to May 28th, 2020, who required IMV or NIV, and survived to hospital discharge were enrolled. Patients were contacted two years after discharge to assess vital status, functional, psychological, and cognitive outcomes using validated scales. Patients with persistent respiratory symptoms or high burden of residual lung damage at previous CT scan received a two-year chest CT scan. RESULTS: Out of 61 IMV survivors, 98% were alive at two-year follow-up, and 52 completed the questionnaire. Out of 82 survivors receiving NIV only, 94% were alive at two years, and 47 completed the questionnaire. We found no major differences between invasively and noninvasively ventilated patients, with overall acceptable functional recovery. Among the 99 patients completing the questionnaire, 23 have more than moderate exertional dyspnea. Chest CT scans showed that 4 patients (all received IMV) had fibrotic-like changes. CONCLUSIONS: Patients who received mechanical ventilation due to COVID-19 and were discharged from hospital had a 96% survival rate at the two-year follow-up. There was no difference in overall recovery and quality of life between patients who did and did not require IMV, although respiratory morbidity remains high.

Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review.

INTRODUCTION: Recent studies suggested that Macklin sign is a predictor of barotrauma in patients with acute respiratory distress syndrome (ARDS). We performed a systematic review to further characterize the clinical role of Macklin. METHODS: PubMed, Scopus, Cochrane Central Register and Embase were searched for studies reporting data on Macklin. Studies without data on chest CT, pediatric studies, non-human and cadaver studies, case reports and series including <5 patients were excluded. The primary objective was to assess the number of patients with Macklin sign and barotrauma. Secondary objectives were: occurrence of Macklin in different populations, clinical use of Macklin, prognostic impact of Macklin. RESULTS: Seven studies enrolling 979 patients were included. Macklin was present in 4-22% of COVID-19 patients. It was associated with barotrauma in 124/138 (89.8%) of cases. Macklin sign preceded barotrauma in 65/69 cases (94.2%) 3-8 days in advance. Four studies used Macklin as pathophysiological explanation for barotrauma, two studies as a predictor of barotrauma and one as a decision-making tool. Two studies suggested that Macklin is a strong predictor of barotrauma in ARDS patients and one study used Macklin sign to candidate high-risk ARDS patients to awake extracorporeal membrane oxygenation (ECMO). A possible correlation between Macklin and worse prognosis was suggested in two studies on COVID-19 and blunt chest trauma. CONCLUSIONS: Increasing evidence suggests that Macklin sign anticipate barotrauma in patients with ARDS and there are initial reports on use of Macklin as a decision-making tool. Further studies investigating the role of Macklin sign in ARDS are justified.

Prognostic value of preoperative CT scan derived body composition measures in resected pancreatic cancer.

BACKGROUND: It remains unclear whether preoperative body composition may affect the prognosis of pancreatic cancer patients undergoing surgery. The aim of the present study was to assess the extent to which preoperative body composition impacts on postoperative complication severity and survival in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC). METHODS: A retrospective cohort study was performed on consecutive patients who underwent pancreatoduodenectomy with preoperative CT scan imaging available. Body composition parameters including total abdominal muscle area (TAMA), visceral fat area (VFA), subcutaneous fat area and liver steatosis (LS) were assessed. Sarcopenic obesity was defined as a high VFA/TAMA ratio. Postoperative complication burden was evaluated with the comprehensive complication index (CCI). RESULTS: Overall, 371 patients were included in the study. At 90 days after surgery, 80 patients (22%) experienced severe complications. The median CCI was 20.9 (IQR 0-30). At multivariate linear regression analysis, preoperative biliary drainage, ASA score ≥3, fistula risk score and sarcopenic obesity (37% increase; 95%CI 0.06-0.74; p = 0.046) were associated to an increase in CCI. Patient characteristics associated to sarcopenic obesity were older age, male gender and preoperative LS. At a median follow-up of 25 months (IQR 18-49), median disease-free survival (DFS) was 19 months (IQR 15-22). At cox-regression analysis, only pathological features were associated with DFS, while LS and other body composition measures did not show any prognostic role. CONCLUSION: The combination of sarcopenia and visceral obesity was significantly associated with increased complication severity after pancreatoduodenectomy for cancer. Patients' body composition did not affect disease free survival after pancreatic cancer surgery.

The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection.

PURPOSE: Patients with COVID-19 infection are frequently found to have pulmonary barotrauma. Recent work has identified the Macklin effect as a radiographic sign that often occurs in patients with COVID-19 and may correlate with barotrauma. METHODS: We evaluated chest CT scans in COVID-19 positive mechanically ventilated patients for the Macklin effect and any type of pulmonary barotrauma. Patient charts were reviewed to identify demographic and clinical characteristics. RESULTS: The Macklin effect on chest CT scan was identified in a total of 10/75 (13.3%) COVID-19 positive mechanically ventilated patients; 9 developed barotrauma. Patients with the Macklin effect on chest CT scan had a 90% rate of pneumomediastinum (p < 0.001) and a trend toward a higher rate of pneumothorax (60%, p = 0.09). Pneumothorax was most frequently omolateral to the site of the Macklin effect (83.3%). CONCLUSION: The Macklin effect may be a strong radiographic biomarker for pulmonary barotrauma, most strongly correlating with pneumomediastinum. Studies in ARDS patients without COVID-19 are needed to validate this sign in a broader population. If validated in a broad population, future critical care treatment algorithms may include the Macklin sign for clinical decision making and prognostication.

Association of IgG4-related disease and systemic rheumatic disorders.

PURPOSE: Autoimmune disorders can occur together especially in genetically predisposed individuals. We here aimed to assess the occurrence of IgG4-related disease (IgG4-RD) in association with other systemic immune-mediated conditions. METHODS: We retrospectively analyzed the clinical records of patients with IgG4-RD followed at the IgG4-RD Clinic of San Raffaele Hospital (Milan, Italy) for pre-existing or concomitant immune-mediated disorders. IgG4-RD was diagnosed based on histological findings and on the 2011 Comprehensive Diagnostic criteria. Associated immune-mediated disorders were diagnosed based on available classification and/or diagnostic criteria. RESULTS: Two-hundred and thirty-four patients with a definitive diagnosis of IgG4-RD were included in this study. A pre-existing immune-mediated connective tissue disease was reported in 6/234 patients (3%): one case each of sarcoidosis, Takayasu arteritis (TA), eosinophilic granulomatosis with polyangitis (EGPA), and rheumatoid arthritis; and two cases of granulomatosis with polyangitis (GPA). Organs involved by IgG4-RD included the lungs, the pancreas, the peritoneum, lacrimal glands, meninges and orbits. Sarcoidosis, EGPA, and TA preceded the onset of IgG4-RD. GPA preceded IgG4-RD onset in one case and occurred simultaneously in the other case. Rheumatoid arthritis occurred together with IgG4-RD in one case. CONCLUSION: Our observation suggests that "secondary" IgG4-RD can present in the context of pre-existing systemic immune-mediated disorders and complicate systemic autoimmune diseases as well as chronic granulomatous conditions. Further studies are needed to define whether this peculiar clinical scenario is associated with different genetic backgrounds, pathological bases, and long-term outcomes.