Clinical outcomes of intermittent panitumumab based-therapy for previously treated older patient with metastatic colorectal cancer: a case report and review of literature.

Background: Metastatic colorectal cancer is one of the most common causes of cancer death worldwide, and its incidence increases with age. Treating an older RAS and BRAF wild-type patient represents a challenge for the medical oncologist, even more so for those patients defined as "vulnerable" and undergoing at least two lines of therapy. In this context, recent evidence supports the role of retreatment with anti-EGFR inhibitors and the use of liquid biopsy. However, frequent skin toxicity constitutes a limitation of therapy, especially in older people. Since it has been described that continuous administration of these monoclonal antibodies leads to acquired resistance to anti-EGFRs, with consequent therapeutic failure, an intermittent strategy with chemotherapy plus an anti-EGFR could help maintain the efficacy of the treatment over time, delaying the resistance and improving patients' quality of life. Case presentation: In this case report, we describe the case of an older RAS and BRAF wild-type patient reporting a clinical response after first-line chemotherapy with FOLFOX + panitumumab, subsequently interrupted in the absence of disease progression. After radiological worsening and two additional lines of therapy, the reintroduction of panitumumab plus 5-fluorouracil, administered with a stop-and-go strategy, allowed the patient to benefit from the same drugs for 2 years from diagnosis, to achieve a clinical response during fourth-line treatment lasting more than 3 years, to delay resistance and to avoid unacceptable anti-EGFR skin toxicity. This patient, who died from a myocardial infarction more than 5 years after diagnosis, represents the case of a good synergy between molecular profile of disease and reintroduction of an anti-EGFR with intermittent strategy.

Safe and Informed Use of Gadolinium-Based Contrast Agent in Body Magnetic Resonance Imaging: Where We Were and Where We Are.

Gadolinium-based contrast agents (GBCAs) have helped to improve the role of magnetic resonance imaging (MRI) for the diagnosis and treatment of diseases. There are currently nine different commercially available gadolinium-based contrast agents (GBCAs) that can be used for body MRI cases, and which are classifiable according to their structures (cyclic or linear) or biodistribution (extracellular-space agents, target/specific-agents, and blood-pool agents). The aim of this review is to illustrate the commercially available MRI contrast agents, their effect on imaging, and adverse reaction on the body, with the goal to lead to their proper selection in different clinical contexts. When we have to choose between the different GBCAs, we have to consider several factors: (1) safety and clinical impact; (2) biodistribution and diagnostic application; (3) higher relaxivity and better lesion detection; (4) higher stability and lower tissue deposit; (5) gadolinium dose/concentration and lower volume injection; (6) pulse sequences and protocol optimization; (7) higher contrast-to-noise ratio at 3.0 T than at 1.5 T. Knowing the patient's clinical information, the relevant GBCAs properties and their effect on body MRI sequences are the key features to perform efficient and high-quality MRI examination.

Accuracy of computed tomography in staging acute appendicitis and its impact on surgical outcome and strategy: a multi-center retrospective case-control study.

INTRODUCTION: The aims of this study were to evaluate the concordance between AAST-CT appendicitis grading criteria, first published in 2014, and surgical findings and to assess the impact of CT staging on the choice of surgical approach. METHODS: This was a multi-center retrospective case-control study including 232 consecutive patients undergoing surgery for acute appendicitis and who had undergone preoperative CT evaluation between 1 January 2017 and 1 January 2022. Appendicitis severity was classified in 5 grades. For each degree of severity, the surgical outcome between patients undergoing open and surgical approach was compared. RESULTS: An almost perfect agreement (k = 0.96) was found between CT and surgery in staging acute appendicitis. The vast majority of patients with grade 1 and 2 appendicitis underwent laparoscopic surgical approach and showed low morbidity rate. In patients with grade 3 and 4 appendicitis, laparoscopic approach was adopted in 70% of cases and was associated, if compared to open, with a higher prevalence of postoperative abdominal collections (p = 0.05; fisher's exact test) and a significantly lower prevalence of surgical site infections (p = 0.0007; fisher's exact test). All the patients with grade 5 appendicitis were treated by laparotomy. CONCLUSIONS: AAST-CT appendicitis grading system seems to show a relevant prognostic value and a potential impact on the choice of surgical strategy, directing toward a laparoscopic approach in patients with grade 1 and 2, an initial laparoscopic approach, replaceable by the open one, for grade 3 and 4 and an open approach in patients with grade 5.

Morphologic, dynamic and high-resolution microscopy MRI in early-onset spondyloarthritis finger dactylitis.

OBJECTIVE: Up to now, the pathophysiology of SpA dactylitis has not been entirely clarified. It is not clear which are the involved tissues and which is the primary lesion of the "sausage-like" digit. The aim of our study was to examine the finger structures in early-onset finger dactylitis using high-resolution microscopy MRI together with morphologic and dynamic MRI. SUBJECTS AND METHODS: In a 6-month period, 13 SpA patients (7 females and 6 males), mean age 54.07 years (range 37-73 years) and mean disease duration 7.07 years (range 1-44 years) with early-onset finger dactylitis (less than 3 months) were recruited. Nine patients had PsA, 3 HLA-B27-positive uSpA and 1 HLA-B27-negative uSpA. One patient had 2 dactylitis fingers. Ten healthy volunteers matched for age and sex with no personal and family history of SpA were enrolled. All dactylitis fingers and randomly selected fingers of the normal control subjects were imaged by morphologic, dynamic and high-resolution microscopy MRI. RESULTS: We have found flexor tenosynovitis in all the 14 dactylitis fingers, joint synovitis in 5 and oedema in the finger soft tissue in 10. In 2 dactylitis fingers, there was oedema at the insertion of the joint capsule suggesting enthesitis. In 5 dactylitis fingers, there was only mild enhancement at the enthesis organ (collateral ligament, flexor and extensor tendons). CONCLUSIONS: Our MRI study on early-onset dactylitis demonstrates that flexor tenosynovitis, joint synovitis and oedema of the digit soft tissue are the predominant alterations visible in the early phase of evolution of dactylitis and that, therefore, enthesitis may not be considered the primary lesion of dactylitis.

Macklin effect on baseline chest CT scan accurately predicts barotrauma in COVID-19 patients.

PURPOSE: To validate the role of Macklin effect on chest CT imaging in predicting subsequent occurrence of pneumomediastinum/pneumothorax (PMD/PNX) in COVID-19 patients. MATERIALS AND METHODS: This is an observational, case-control study. Consecutive COVID-19 patients who underwent chest CT scan at hospital admission during the study time period (October 1st, 2020-April 31st, 2021) were identified. Macklin effect accuracy for prediction of spontaneous barotrauma was measured in terms of sensitivity, specificity, positive (PPV) and negative predictive values (NPV). RESULTS: Overall, 981 COVID-19 patients underwent chest CT scan at hospital arrival during the study time period; 698 patients had radiological signs of interstitial pneumonia and were considered for further evaluation. Among these, Macklin effect was found in 33 (4.7%), including all 32 patients who suffered from barotrauma lately during hospital stay (true positive rate: 96.9%); only 1/33 with Macklin effect did not develop barotrauma (false positive rate: 3.1%). No barotrauma event was recorded in patients without Macklin effect on baseline chest CT scan. Macklin effect yielded a sensitivity of 100% (95% CI: 89.1-100), a specificity of 99.85% (95% CI: 99.2-100), a PPV of 96.7% (95% CI: 80.8-99.5), a NPV of 100% and an accuracy of 99.8% (95% CI: 99.2-100) in predicting PMD/PNX, with a mean advance of 3.2 ± 2.5 days. Moreover, all Macklin-positive patients developed ARDS requiring ICU admission and, in 90.1% of cases, invasive mechanical ventilation. CONCLUSIONS: Macklin effect has high accuracy in predicting PMD/PNX in COVID-19 patients; it is also an excellent predictor of disease severity.

Radiologist-rheumatologist multidisciplinary approach in the management of axial spondyloarthritis: a Delphi consensus statement.

OBJECTIVES: The aim of this study was to develop a Delphi consensus statement between rheumatologists and radiologists for the diagnosis and monitoring of axial spondyloarthritis (axial-SpA). METHODS: Following an extensive literature search to identify unmet needs and potential goals for a multidisciplinary approach, a scientific board comprising 28 Italian hospital-based rheumatologists (n=19) and radiologists (n=9) identified 8 "starting points", resulting in the development of 23 consensus statements covering issues from current practice guidelines to specific MRI protocols for the assessment of axial-SpA. Each participant anonymously expressed a level of agreement for each statement using a 5-point Likert scale (1="strongly disagree"; 5="strongly agree") via an online Delphi method.Total cumulative agreement (TCA) was defined as the sum of the percentage of response to items 4 ("agree") and 5 ("absolutely agree"). Consensus was defined as ≥80% total cumulative agreement for each statement. RESULTS: After the first round of voting (28 participants), positive consensus was reached for 28/31 (90.3%) statements. Statements without consensus (n=3) were discussed in a face-to-face plenary session prior to the second vote (28 participants). After the second round voting, positive consensus was attained for all 31 statements, with mean final TCA of 95.5% (range 82.1-100%). CONCLUSIONS: This Delphi consensus statement provides an aid to rheumatologists and radiologists for the diagnosis and monitoring of axial-SpA.

Unexpected and durable response with regorafenib in a metastatic colorectal cancer patient without KDR mutation: A case report.

RATIONALE: Regorafenib is an oral multikinase inhibitor and is approved as salvage therapy in the standard treatment of advanced colorectal cancer (CRC). Due to its limited efficacy, toxicity profile, and cost, it is necessary to identify those patients who may have the most benefit from regorafenib. In a previous case report, kinase insert domain receptor (KDR) mutation has been associated with exceptional clinical response (CR) in an elderly patient treated with a low dose of regorafenib; thus, it was hypothesized that it could represent a new predictive marker of drug response. PATIENT CONCERNS: A heavily pretreated 67-year-old man with a wide peripancreatic recurrence of colon carcinoma and liver metastases was subjected to treatment with regorafenib. DIAGNOSES: After 3 months of therapy, a computed tomography scan showed an impressive reduction of disease. INTERVENTIONS: Regorafenib was given at full doses (160 mg/die for 21 days, every 4 weeks). OUTCOMES: A lasting response without relevant toxicity. No KDR mutation relief was detected. After 13 months from the start of treatment, the patient died after the diagnosis of encephalic metastases. LESSONS: Regorafenib can lead to an unexpected and durable CR with consistent progression-free survival and overall survival benefit even in patients affected by polychemotherapy refractory metastatic CRC. Further studies are needed to establish the benefit of KDR mutation as predictive marker for regorafenib sensitivity for patients with CRC. We include a detailed revision of prognostic and predictive factors of clinical outcome identified in literature to optimize the use of regorafenib in this setting.

Nontraumatic adrenal hemorrhage: the adrenal stress.

Bilateral adrenal hemorrhage is a rare condition, which is burdened by potentially life-threatening consequences related to the development of acute adrenal insufficiency. Despite treatment with stress-dose glucocorticoids, a mortality rate of 15% has been reported, which varies according to the severity of underlying predisposing illness and could be much more higher if the adrenal insufficiency is not promptly recognized. An early diagnosis is crucial, though, because of nonspecific clinical and laboratory findings, adrenal hemorrhage is rarely suspected. Therefore, imaging has a pivotal role for the diagnosis of this uncommon condition but, despite adrenal hematomas characteristically appear round or oval with peripheral fat stranding, their initial presentation could be ambiguous. The authors describe a case of postoperative bilateral adrenal hemorrhage initially presenting at computed tomography scan as thickening of both glands surrounded by fat stranding, which led to close monitoring of adrenal function before unequivocal hemorrhage developed.

Idiopathic Renal Infarction Mimicking Appendicitis.

Renal infarction is a rare cause of referral to the emergency department, with very low estimated incidence (0.004%-0.007%). Usually, it manifests in patients aged 60-70 with risk factors for thromboembolism, mostly related to heart disease, atrial fibrillation in particular. We report a case of idiopathic segmental renal infarction in a 38-year-old patient, presenting with acute abdominal pain with no previous known history or risk factors for thromboembolic diseases. Because of its aspecific clinical presentation, this condition can mimic more frequent pathologies including pyelonephritis, nephrolithiasis, or as in our case appendicitis. Here we highlight the extremely ambiguous presentation of renal infarct and the importance for clinicians to be aware of this condition, particularly in patients without clear risk factors, as it usually has a good prognosis after appropriate anticoagulant therapy.

Cystic dystrophy of the duodenal wall in heterotopic pancreas: an atypical case in non-alcoholic female.

Cystic dystrophy of the duodenal wall in heterotopic pancreas, recently described as paraduodenal pancreatitis, is a rare condition characterized by multiple cysts or pseudocysts located in the submucosa or muscularis propria of a thickened duodenal wall. They result from multiple episodes of obstruction of the small ducts in aberrant pancreatic islets. Cystic dystrophy of the duodenal wall in heterotopic pancreas usually affects alcoholic males, but here we present the case of a female without a history of alcohol abuse who was referred to our emergency department with abdominal pain and vomiting. She was treated by a pancreas-preserving surgical approach, thanks to a proper pre-operative differential diagnosis. Even though differentiating this benign condition from pancreatic cancer is a challenge, some characteristic findings on multidetector CT scan and MRI/MR cholangiopancreatography, such as a thickened duodenal wall containing cysts and sheet-like tissues in the pancreaticoduodenal groove, could lead to the correct diagnosis.

Low frequency of axial involvement in southern Italian Caucasian children with HLA-B27 positive juvenile onset undifferentiated spondyloarthritis.

OBJECTIVES: To establish how many children with HLA B27-positive juvenile undifferentiated spondyloarthritis (JuSpA) living in southern Italy develop axial disease after 5 years of disease. METHODS: All children with B27-positive enthesitis-related arthritis (ERA) consecutively seen in a 7-year period were entered in a special register and were followed prospectively. Each patient was examined at 6-month intervals, even if asymptomatic. In patients with inflammatory spinal pain and/or buttock pain, MRI of the sacroiliac joints and spine was performed. Five years after inclusion, sacroiliac joint plain radiographs were obtained and read blindly after being mixed with those of control subjects. RESULTS: Thirteen children, 9 boys and 4 girls, with B27-positive ERA and one girl with B27-positive isolated SpA dactylitis were seen in the study period. Their median age at disease onset and at our first examination were 10 (range 2-16) and 12 years (range 3-16), respectively. During follow-up, only one patient had axial symptoms, i.e. alternate buttock pain. MRI revealed moderate bone oedema at both sacroiliac joints. After five years of disease, no patient showed reduced spinal movement. No sign of sacroiliitis was seen in any patient and control on plain films. A new MRI of the sacroiliac joints of the patient who showed bone oedema in the first years of disease was normal. CONCLUSIONS: This study confirms that the onset of axial involvement in Italian Caucasian HLA-B27 positive children with ERA is rare in the first five years of disease.

Fast spin echo-T2-weighted sequences with fat saturation in toe dactylitis of spondyloarthritis.

We aimed to establish by using fast spin echo (FSE)-T2-weighted sequences with fat saturation if flexor tendon enthesitis is the primary lesion in spondyloarthritis (SpA) toe dactylitis. Consecutive patients showing toe dactylitis and meeting Amor criteria for the classification of SpA were enrolled. Dactylitic toes and their corresponding normal contralateral digits were studied by FSE-T2-weighted sequences with fat saturation. Twelve dactylitic toes belonging to ten SpA patients were studied. All dactylitic toes showed mild-to-moderate fluid collection in the synovial sheaths of flexor digitorum brevis and longus. Involvement of joint cavity was simultaneously seen in at least one joint of eight (66.6%) out of the 12 toes. A mild-to-severe peritendinous soft tissue edema was observed in all but one of the affected toes. In no dactylitic toe was bone edema observed either near the insertions of the flexor digitorum brevis and longus tendons or in other sites of the phalanges. No lesions were observed in the 12 contralateral clinically normal toes. In SpA toe dactylitis there is no evidence of enthesitis of the flexor digitorum brevis and longus tendons and joint capsules.