Magnetic resonance imaging for acute appendicitis in pregnancy: can clinical scores predict when imaging is needed?

PURPOSE: Advanced imaging may augment the diagnostic milieux for presumed acute appendicitis (AA) during pregnancy, however it is not clear when such imaging modalities are indicated. The aim of this study was to assess the sensitivity and specificity of clinical scoring systems with the findings on magnetic resonance imaging (MRI) of AA in pregnant patients. METHODS: A retrospective cohort study between 2019 and 2021 was performed in two tertiary level centers. Pregnant patients presenting with suspected AA and non-diagnostic trans-abdominal ultrasound who underwent MRI as part of their evaluation were identified. Patient demographics, parity, gestation, presenting signs, and symptoms were documented. The Alvarado and Appendicitis Inflammatory Response (AIR) score for each patient were calculated and correlated with clinical and MRI findings. Univariate analysis was used to identify factors associated with AA on MRI. RESULTS: Of the 255 pregnant patients who underwent MRI, 33 (13%) had findings of AA. On univariate analysis, presentation during the second/third trimester, migration of pain, vomiting and RLQ tenderness correlated with MRI findings of AA. Whilst 5/77 (6.5%) of patients with an Alvarado score ≤4 had signs of AA on MRI, a score of ≥5 had a sensitivity, specificity, negative and positive predictive value of 84.8%, 36.6%, 94.0% and 17.2%. For an AIR score ≥ 5, this was 78.8%, 41.5%, 93.0%, and 16.7%, respectively. CONCLUSIONS: Whilst clinical scoring systems may be useful in identifying which pregnant patients require MRI to be performed when AA is suspected, the low sensitivity implies further research is needed to refine the use of this valuable resource.

Age-related Changes of the Prostate on Magnetic Resonance Imaging: Quantitative and Qualitative Evaluation in a Screening Cohort of BRCA Mutation Carriers.

BACKGROUND: Age-related changes in multiparametric magnetic resonance imaging (mpMRI) of the prostate have been reported in the general population but not in screening cohorts. OBJECTIVES: To evaluate age-related changes on prostatic mpMRI in a screening cohort of BRCA1/2 mutation carriers. METHODS: Asymptomatic BRCA1/2 mutation carriers underwent mpMRI as part of a screening program. All included patients were followed for 3 years with no evidence of prostate cancer. mpMRIs were retrospectively evaluated by two abdominal radiologists for peripheral zone (PZ) patterns on T2 (homogenous hyperintensity, wedge-shaped hypointensities, patchy hypointensities, or diffuse hypointensity), and transition zone (TZ) pattern on T2 (homogenous, heterogeneous, nodular). Apparent diffusion coefficient (ADC) values of PZ and TZ were measured. Statistical analysis was performed using a predefined age cutoff of 50 years old. RESULTS: Overall, 92 patients were included: 38 in the younger age group (40-49 years) and 54 in the older age group (50-69 years). PZ homogenous hyperintensity and wedge-shaped hypointensities were more common in the older patients, whereas diffuse hypointensity was more common in younger patients (P < 0.001 for both readers) with substantial inter-reader agreement between the readers (kappa=0.643). ADC values were lower in young patients in the PZ (P < 0.001) and TZ (P = 0.003). CONCLUSIONS: Age-related differences in mpMRI were validated in BRCA mutation carriers. As some features overlap with prostatic carcinoma, awareness is crucial, specifically to diffuse T2 hypointensities of the PZ and lower ADC values in the PZ and TZ, which are more common in younger patients.

Diffusion Is Directional: Innovative Diffusion Tensor Imaging to Improve Prostate Cancer Detection.

In the prostate, water diffusion is faster when moving parallel to duct and gland walls than when moving perpendicular to them, but these data are not currently utilized in multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) detection. Diffusion tensor imaging (DTI) can quantify the directional diffusion of water in tissue and is applied in brain and breast imaging. Our aim was to determine whether DTI may improve PCa detection. We scanned patients undergoing mpMRI for suspected PCa with a DTI sequence. We calculated diffusion metrics from DTI and diffusion weighted imaging (DWI) for suspected lesions and normal-appearing prostate tissue, using specialized software for DTI analysis, and compared predictive values for PCa in targeted biopsies, performed when clinically indicated. DTI scans were performed on 78 patients, 42 underwent biopsy and 16 were diagnosed with PCa. The median age was 62 (IQR 54.4-68.4), and PSA 4.8 (IQR 1.3-10.7) ng/mL. DTI metrics distinguished PCa lesions from normal tissue. The prime diffusion coefficient (λ1) was lower in both peripheral-zone (p < 0.0001) and central-gland (p < 0.0001) cancers, compared to normal tissue. DTI had higher negative and positive predictive values than mpMRI to predict PCa (positive predictive value (PPV) 77.8% (58.6-97.0%), negative predictive value (NPV) 91.7% (80.6-100%) vs. PPV 46.7% (28.8-64.5%), NPV 83.3% (62.3-100%)). We conclude from this pilot study that DTI combined with T2-weighted imaging may have the potential to improve PCa detection without requiring contrast injection.

A noninferiority within-person study comparing the accuracy of transperineal to transrectal MRI-US fusion biopsy for prostate-cancer detection.

BACKGROUND: Magnetic resonance imaging (MRI) and ultrasound (US) fusion prostate-biopsies can be performed in a transrectal (TR-fusion) or transperineal (TP-fusion) approach. Prospective comparative evidence is limited. In this study we compared the detection rate of clinically-significant prostate-cancer (csPCa) within an index lesion between TR and TP-fusion. PATIENTS AND METHODS: This was a prospective, noninferiority, and within-person trial. Men scheduled for MRI-US-fusion with a discrete MRI PI-RRAD ≥ 3 lesion were included. A dominant index lesion was determined for each subject and sampled by TR and TP-fusion during the same session. The order of biopsies was randomized and equipment was reset to avoid chronological and incorporation bias. For each subject, the index lesion was sampled 4-6 times in each approach. All biopsies were performed using Navigo fusion software (UC-Care, Yokneam, Israel). csPCa was defined as: Grade Group ≥ 2 or cancer-core length ≥ 6 mm. We used a noninferiority margin of 10% and a one-sided alpha level of 5%. RESULTS: Seventy-seven patients completed the protocol. Median age was 68.2 years (IQR:64.2-72.2), median PSA was 8.9 ng/ml (IQR:6.18-12.2). Ten patients (13%) were biopsy naive, others (87%) had a previous biopsy. csPCa was detected in 32 patients (42%). All of these cases were detected by TP-fusion, while only 20 (26%) by TR-fusion. Absolute difference for csPCa diagnosis was 15.6 (CI 90% 27.9-3.2%) in favor of TP-fusion (p = 0.029). TP-fusion was noninferior to TR-fusion. The lower boundary of the 90% confidence-interval between TP-fusion and TR-fusion was greater than zero, therefore TP-fusion was also found to be superior. Exploratory subgroup analyses showed TP-fusion was consistently associated with higher detection rates of csPCa compared with TR-fusion in patient and index-lesion derived subgroups (size, location, PI-RADS, PSA, and biopsy history). CONCLUSIONS: In this study, TP-fusion biopsies were found to be noninferior and superior to TR-fusion biopsies in detecting csPCa within MRI-visible index lesion. Centers experienced in both TP and TR-fusion should consider these results when choosing biopsy method.

A phase I clinical trial of dTCApFs, a derivative of a novel human hormone peptide, for the treatment of advanced/metastatic solid tumors.

The aim of the present phase I first-in-human study was to investigate the safety/efficacy of dTCApFs (a novel hormone peptide that enters cells through the T1/ST2 receptor), in advanced/metastatic solid tumors. The primary objective of this open-label dose-escalation study was to determine the safety profile of dTCApFs. The study enrolled patients (aged ≥18 years) with pathologically confirmed locally advanced/metastatic solid malignancies, who experienced treatment failure or were unable to tolerate previous standard therapy. The study included 17 patients (64% male; median age, 65 years; 47% colorectal cancer, 29% pancreatic cancer). The patients received 1-3 cycles of escalating dTCApFs doses (6-96 mg/m2). The mean number ± standard deviation of treatment cycles/patient was 3.2±1.4; no dose-limiting toxicities were observed up to a dose of 96 mg/m2, and the maximum tolerated dose was not reached. Half-life, maximal plasma concentration, and dTCApFs exposure were found to be linearly correlated with dose. Five patients were treated for ≥3 months (12, 24, 48 mg/m2) and experienced stable disease throughout the treatment period, and 1 experienced pathological complete response. Analysis of serum biomarkers revealed decreased levels of angiogenic factors at dTCApFs concentrations of 12-48 mg/m2, increased levels of anticancer cytokines, and induction of the endoplasmic reticulum (ER) stress biomarker GRP78/BiP. Efficacy and biomarker data suggest that patients whose tumors were T1/ST2-positive exhibited a better response to dTCApFs. In conclusion, dTCApFs was found to be safe/well-tolerated, and potentially efficacious, with linear pharmacokinetics. Consistent with preclinical studies, the mechanism through which dTCApFs exerts anticancer effects appears to involve induction of ER stress, suppression of angiogenesis, and activation of the innate immune response. However, further studies are warranted.

Stereotactic body radiation therapy (SBRT) for definitive treatment and as a bridge to liver transplantation in early stage inoperable Hepatocellular carcinoma.

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) is an emerging modality for definitive treatment of Hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included all early stage HCC patients who were not candidates for primary resection and/or local therapy, treated with SBRT between 11/2011 and 1/2016. RESULTS: Twenty-three patients were included. The median age was 62 years; 70% males; 30% females; 70% viral hepatitis carriers; 100% cirrhotic; 13 Child Pugh [CP]-A and 10 [CP]-B. The median tumor volume was 12.7cm3 (range, 2.2-53.6 cm3). Treatment was well tolerated. With the exception of one patient who developed RILD, no other patient had significant changes in 12 weeks of laboratory follow-up. SBRT was a bridge to transplantation in 16 patients and 11 were transplanted.. No surgical difficulties or complications were reported following SBRT, and none of the transplanted patients had local progression before transplantation. The median prescribed dose to the tumor was 54Gy (range, 30-54Gy), the median dose to the uninvolved liver was 6.0Gy(range, 1.6-12.6Gy). With a median follow-up time of 12 months, the median overall-survival for the 11 transplanted patients was not reached (range, 2.0-53.7+ months) and was 23 months for the 12 non-transplanted patients. The median progression-free survival for the transplanted patients was not reached (54+ months) and was 14.0 months for the non-transplanted patients. There was no SBRT-related mortality. Liver explant post SBRT revealed pathological complete response in 3(27.3%), pathological partial response in 6(54.5%), and pathological stable disease in 2(18.2%) tumors. CONCLUSIONS: SBRT is safe and effective and can be used as a bridge to transplantation without comprising the surgical procedure.

Radiotherapy and Sorafenib in the Management of Patients with Hepatocellular Carcinoma Have Led to Improved Survival: A Single Center Experience.

BACKGROUND & AIMS: Hepatocellular Carcinoma (HCC) is the sixth most common malignancy and the third most common cause of cancer mortality worldwide. We aimed to assess the effect of novel treatment options on the survival of HCC patients. METHODS: This retrospective study included all HCC patients diagnosed between 2000 and 2013 referred to the Davidoff center and treated by a multidisciplinary team. RESULTS: The analysis included 321 patients (median age, 64 years; 74.8% males; 74.1% viral carriers; 76.0% cirrhosis; 56.7% diagnosis at an early stage). The estimated hazard ratio by multivariate analysis for the effect of the period of diagnosis (2007-2013 vs. 2000-2006) on survival was 0.72 (95% CI: 0.54-0.96; p=0.027). There was no difference in the distribution by CP score, by BCLC stage at diagnosis or in the proportion of patients undergoing surgical procedures (liver transplantation or resection). In the later time frame, there was a significant decrease in the proportion of patients undergoing percutaneous treatments (14.6% vs.4.2%, p=0.004) and embolization (46.9% vs.24.6%, p=0.001), and a significant increase in radiotherapy (1.5% vs. 8.4%, p=0.009) and treatment with sorafenib (6% vs. 18.3%, p=0.002). CONCLUSION: Technological/pharmaceutical innovations have led to advancement in HCC treatment. Since there was no significant difference in the proportion of patients undergoing surgical procedures during the evaluated timeframe, the improved survival may stem from better management of advanced stage patients by a multidisciplinary team.

Personalized prostate cancer screening among men with high risk genetic predisposition- study protocol for a prospective cohort study.

BACKGROUND: Prostate cancer screening among the general population is highly debatable. Nevertheless, screening among high-risk groups is appealing. Prior data suggests that men carrying mutations in the BRCA1& 2 genes may be at increased risk of developing prostate cancer. Additionally, they appear to develop prostate cancer at a younger age and with a more aggressive course. However, prior studies did not systematically perform prostate biopsies and thus cannot determine the true prevalence of prostate cancer in this population. METHODS: This will be a prospective diagnostic trial of screening for prostate cancer among men with genetic predisposition. The target population is males (40-70 year old) carrying a BRCA1 and/or BRCA2 germ line mutation. They will be identified via our Genetic counseling unit. All men after signing an informed consent will undergo the following tests: PSA, free to total PSA, MRI of prostate and prostate biopsy. The primary endpoint will be to estimate the prevalence, stage and grade of prostate cancer in this population. Additionally, the study aims to estimate the impact of these germ line mutations on benign prostatic hyperplasia. Furthermore, this study aims to create a bio-bank of tissue, urine and serum of this unique cohort for future investigations. Finally, this study will identify an inception cohort for future interventional studies of primary and secondary prevention. DISCUSSION: The proposed research is highly translational and focuses not only on the clinical results, but on the future specimens that will be used to advance our understanding of prostate cancer patho-physiology. Most importantly, these high-risk germ-line mutation carriers are ideal candidates for primary and secondary prevention initiatives. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02053805.

CF102 for the treatment of hepatocellular carcinoma: a phase I/II, open-label, dose-escalation study.

BACKGROUND: The A(3) adenosine receptor (A(3)AR) is overexpressed in the tumor and in the peripheral blood mononuclear cells of patients with hepatocellular carcinoma (HCC). The orally active drug candidate CF102, an A(3)AR agonist, induces apoptosis of HCC cells via deregulation of the Wnt signaling pathway. In this open label phase I/II trial, the safety and clinical effects of CF102 were assessed in patients with advanced unresectable HCC. METHODS: The primary objectives of this trial were to examine the safety and pharmacokinetic (PK) behavior of CF102 given orally (1, 5, and 25 mg BID) in 28-day cycles. Evaluation of anti-tumor effects and the utilization of A(3)AR as a biological predictive marker of response to CF102 were the secondary objectives. RESULTS: Eighteen patients received CF102-six at each dose level. No serious drug-related adverse events or dose-limiting toxicities were observed. CF102 demonstrated good oral bioavailability and linear PK behavior. Median overall survival in the study population, 67% of whom had received prior sorafenib, was 7.8 months, and for Child Pugh B patients (28%) it was 8.1 months. Stable disease by RECIST was observed in four patients for at least 4 months. CF102 maintained liver function over a 6-month period. A correlation between receptor overexpression levels at baseline and patients' overall survival was found. One of the patients who presented with skin nodules that were biopsy-proven to be HCC metastases prior to the trial showed complete metastasis regression during three months of treatment with CF102. CONCLUSIONS: CF102 is safe and well-tolerated, showing favorable PK characteristics in Child Pugh A and B HCC patients, justifying further clinical development.

Computed tomography angiography in pulmonary hypertension.

BACKGROUND: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers. OBJECTIVES: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests. METHODS: The study included 38 patients with PHT who underwent CT angiography and HRCT as part of their routine evaluation. Diagnoses included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39-92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40-135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans of patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group. RESULTS: Mean main pulmonary artery diameter in the study group was 3.55 +/- 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 +/- 0.29, right pulmonary artery 2.63 +/- 0.49 cm, left pulmonary artery 2.57 +/- 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated with the pressure measurement by echocardiography (P=0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study. CONCLUSIONS: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

Post-traumatic soft tissue tumors: case report and review of the literature a propos a post-traumatic paraspinal desmoid tumor.

BACKGROUND: Antecedent trauma has been implicated in the causation of soft tissue tumors. Several criteria have been established to define a cause-and-effect relationship. We postulate possible mechanisms in the genesis of soft tissue tumors following antecedent traumatic injury. CASE PRESENTATION: We present a 27-year-old woman with a paraspinal desmoid tumor, diagnosed 3-years following a motor vehicle accident. Literature is reviewed. CONCLUSION: Soft tissue tumors arising at the site of previous trauma may be desmoids, pseudolipomas or rarely, other soft tissue growths. The cause-and-effect issue of desmoid or other soft tissue tumors goes beyond their diagnosis and treatment. Surgeons should be acquainted with this diagnostic entity as it may also involve questions of longer follow-up and compensation and disability privileges.

Enhancing component on CT to predict malignancy in cystic renal masses and interobserver agreement of different CT features.

OBJECTIVE: The objective of our study was to determine the CT features of complex cystic renal masses that are the most predictive of malignancy and to assess interobserver variability when interpreting these features. MATERIALS AND METHODS: Two radiologists blinded to pathology results retrospectively reviewed CT scans of 36 consecutive cystic renal masses in 30 patients (19 men and 11 women; age range, 28-76 years; mean age, 59 +/- 13 years) who had undergone surgery. The study population included only masses with a cystic component on gross pathology and imaging. All patients underwent contrast-enhanced CT. The reviewers recorded the CT features of each cystic mass, including the presence of enhancing components. Accuracy values and odds ratio to predict malignancy were calculated for each CT feature. Weighted kappa was used to measure interobserver agreement. RESULTS: There were 21 cystic renal cell cancers and 11 benign cystic lesions. All cystic renal cell carcinomas showed an enhancing septal or nodular component. The mean sensitivity and specificity of the two reviewers in predicting malignancy for the presence of septal enhancement were 83% (95% confidence interval [CI], 65-93%) and 82% (95% CI, 56-94%); for nodular enhancement, 67% (95% CI, 49-81%) and 96% (95% CI, 75-99%); and for either septal or nodular enhancement, 100% (95% CI, 86-100%) and 86% (95% CI, 67-95%), respectively. The interobserver agreements for septal and nodular enhancement were good (kappa = 0.67) and moderate (kappa = 0.57), respectively. CONCLUSION: The presence of either nodular or septal enhancement shows the highest sensitivity for predicting malignancy with moderate to good interobserver agreement.

Sonographic diagnosis of right segmental omental infarction.

PURPOSE: The purpose of this study was to identify the characteristic features of omental infarction so that this entity can be differentiated from other acute conditions in the right lower quadrant of the abdomen. METHODS: A retrospective review was undertaken. We searched our hospital medical records and found 6 patients with the diagnosis of omental infarction in the last 3 years. Clinical, sonographic, and CT findings at the time of hospital admission and at follow-up were studied. RESULTS: In 5 of the 6 patients (83%) sonography demonstrated a moderately hyperechoic, noncompressible ovoid mass located in the omental fat between the umbilicus and the right colon corresponding to the point of maximal tenderness or to the site of a palpable lesion on physical examination. In 1 patient, sonography revealed no abnormalities. In all patients, the diagnosis of omental infarction was confirmed by CT. One patient underwent laparoscopy because of intractable pain; laparoscopy revealed a necrotic segment in the omentum, and pathologic analysis confirmed the original diagnosis. CONCLUSIONS: Omental infarction is a benign self-limited disease that can mimic acute abdomen. The diagnosis can be established preoperatively with sonography and CT, which may avoid unnecessary laparotomy.