Fatal pulmonary thromboembolism associated with uterine carcinosarcoma

Uterine carcinosarcoma (USC), also known as malignant mixed Müllerian tumor, is a rare and high-grade endometrial cancer composed of epithelial and mesenchymal elements.1 UCS accounts for 4.3% of all uterine corpus cancer, with a worldwide annual incidence of 0.5-3.3 cases per 100.000 women.1 Common risk factors include obesity, nulliparity, chronic endogenous or exogenous hyperestrogenism exposure, older age (with a median age of 70 years), African-American ethnicity, genetic predisposition, tamoxifen therapy, and prior pelvic irradiation.2 Typical UCS-related symptoms, unfortunately, associated with an already advanced stage of the disease, are large masses occupying the abdominal cavity, postmenopausal metrorrhagia, and abdominal pain. One of the most important complications of endometrial tumors, especially in UCS, is venous thromboembolism (VTE), with an incidence of 8.1%.3-4 It may also involve pulmonary arteries and is usually associated with aggressive tumor characteristics and poor patient health.3-4 While Trans-Vaginal Sonography (TVS) is the first-line method for the assessment of UCS, as it can detect neoformations of the myometrium, diagnosis can usually be made by the histopathological examination of targeted endometrial biopsies, possibly associated with hysteroscopy.5-6 Magnetic resonance imaging (MRI) is the best imaging modality for staging. Furthermore, it shows a typical high enhancement with a “spotty” distribution, which may suggest bleeding and is a distinct hallmark of carcinosarcoma.6-7 Depending on the histopathologic assessment of the tumor (depth of invasion and presence or absence of metastases) and clinical presentation,8 the management of UCS requires a multimodality treatment comprised of surgery, systemic therapy, and radiotherapy. The estimated 5-year survival rate ranges from 33 to 39%, but the recurrence rate remains high.2,8 Figure 1 refers to a 61-year-old woman found dead in her flat, dressed in a sanitary napkin and a nightgown. Because the woman lived alone and had no family members, no health information could be achieved. An autopsy was performed to determine the cause of death. The body was in a good state of preservation; it weighed 85 kg and was 158 cm long (BMI = 34 Kg/m2 - Class I obesity). The sanitary napkin was smeared with a yellow-green-blackish creamy material upon external examination,. At dissection, both branches of the pulmonary artery trunk were occupied by red-brownish clots with multiple whitish streaks extending along the intraparenchymal course of the dividing branches of the pulmonary arteries (Figure 1A). They appeared to adhere tenaciously to the intimal surface, replicating the shape of the vascular lumen as a mold. All these characteristics were confirmed upon slicing, and a friable consistency was noted. On the abdominal incision, abundant yellow-green-blackish material of pasty consistency and purulent appearance was noted near the pelvic notch and between some intestinal loops. The uterus (longitudinal diameter = 18 cm, transversal = 11 cm, anteroposterior = 5 cm) appeared to be increased in volume, and the wall had a wall thickness of 1.5 cm. Inside the uterine cavity, a vegetative neoformation was detected (longitudinal diameter = 6 cm, transversal = 5 cm, anteroposterior = 4 cm), almost occluding the lumen. It was associated with abundant material resembling in color and consistency that was found in the abdomen. This neoformation adhered to the lateral walls and fundus of the uterus, extending almost to the cervix (Figure 1B). The ovaries were unscathed. Figure 1 A - Macroscopic view of lungs showing red-brownish clots in the pulmonary artery trunk extending along the intraparenchymal branches (scale bar= 8 cm); B - Macroscopic view of the uterus after dissection with a vegetative neoformation almost occluding its lumen, in association with abundant yellow-green-blackish material of pasty consistency (scale bar= 7 cm); C - Photomicrograph of the endometrial tumor with remnants of neoplastic glandular epithelial component and of residual glandular pseudo-lumen with multi-layered epithelium and cellular atypia (H&E, 200x); D - Photomicrograph of the endometrial tumor with sarcomatous component partly with fused cellularity, partly in the form of compact bundles with marked nuclear atypia and partly with a myxoid-like structure with foci arranged in bundles associated with a scattered cell neoplastic component (H&E; 100x).: Histopathologic examination of the mass revealed features of carcinosarcoma consisting almost entirely of a sarcomatous component and small foci of endometrioid- type adenocarcinoma, with neoplastic embolization of the intraparietal venous vessels. An inflammatory infiltrate associated with marked tumor necrosis was also noted (Figures 1C and 1D). With this background, the abdominal findings were interpreted as purulent discharge and necrosis following the adjoining uterine cancer. At the end of all investigations, the cause of death was identified as massive pulmonary arterial thrombosis in a subject with uterine carcinosarcoma. For completeness, we also considered peritonitis and sepsis as possible co-participation in the cause of death. However, we considered this hypothesis unlikely based on the macroscopic and microscopic findings. Specifically, the peritoneum, abdominal viscera, and serosa were shiny, without fibrinous deposits, and of normal consistency. The purulent-looking material appeared free and not adherent to the abdominal wall and intestinal loops, as would be the case with recent extravasation, and was not organized. The histologic findings confirmed these considerations, which revealed no evidence of septic embolism. Overall, there were no postmortem findings suggestive of peritonitis and sepsis. Had the massive and acutely fatal pulmonary arterial thrombosis not occurred, local or systemic septic complications most likely could have developed. The case was considered of interest because of the rare neoplasm, its size, and the very advanced stage of the disease. Another peculiarity was that one of the most lethal direct complications of this neoplasm, pulmonary arterial thrombosis, was observed. Unfortunately, the absence of family members and health information does not allow further clinical considerations, but the severity of the disease found is glaringly the result of neglected and untreated disease. This case demonstrates that such scenarios are still possible today, despite the increased importance of prevention campaigns. In this context, the observed anatomopathological findings are crucial as they enrich the knowledge of uterine carcinosarcoma, and their images may help forensic pathologists who have not previously encountered this rare disease

Influence of PCL and PHBV on PLLA Thermal and Mechanical Properties in Binary and Ternary Polymer Blends

PLLA, PCL and PHBV are aliphatic polyesters which have been researched and used in a wide range of medical devices, and all three have advantages and disadvantages for specific applications. Blending of these materials is an attractive way to make a material which overcomes the limitations of the individual polymers. Both PCL and PHBV have been evaluated in polymer blends with PLLA in order to provide enhanced properties for specific applications. This paper explores the use of PCL and PHBV together with PLLA in ternary blends with assessment of the thermal, mechanical and processing properties of the resultant polymer blends, with the aim of producing new biomaterials for orthopaedic applications. DSC characterisation is used to demonstrate that the materials can be effectively blended. Blending PCL and PHBV in concentrations of 5-10% with PLLA produces materials with average modulus improved by up to 25%, average strength improved by up to 50% and average elongation at break improved by 4000%, depending on the concentrations of each polymer used. PHBV impacts most on the modulus and strength of the blends, whilst PCL has a greater impact on creep behaviour and viscosity. Blending PCL and PHBV with PLLA offers an effective approach to the development of new polyester-based biomaterials with combinations of mechanical properties which cannot be provided by any of the materials individually

Fatal pulmonary thromboembolism associated with uterine carcinosarcoma

Uterine carcinosarcoma (USC), also known as malignant mixed Müllerian tumor, is a rare and high-grade endometrial cancer composed of epithelial and mesenchymal elements.1 UCS accounts for 4.3% of all uterine corpus cancer, with a worldwide annual incidence of 0.5-3.3 cases per 100.000 women.1 Common risk factors include obesity, nulliparity, chronic endogenous or exogenous hyperestrogenism exposure, older age (with a median age of 70 years), African-American ethnicity, genetic predisposition, tamoxifen therapy, and prior pelvic irradiation.2 Typical UCS-related symptoms, unfortunately, associated with an already advanced stage of the disease, are large masses occupying the abdominal cavity, postmenopausal metrorrhagia, and abdominal pain. One of the most important complications of endometrial tumors, especially in UCS, is venous thromboembolism (VTE), with an incidence of 8.1%.3-4 It may also involve pulmonary arteries and is usually associated with aggressive tumor characteristics and poor patient health.3-4 While Trans-Vaginal Sonography (TVS) is the first-line method for the assessment of UCS, as it can detect neoformations of the myometrium, diagnosis can usually be made by the histopathological examination of targeted endometrial biopsies, possibly associated with hysteroscopy.5-6 Magnetic resonance imaging (MRI) is the best imaging modality for staging. Furthermore, it shows a typical high enhancement with a “spotty” distribution, which may suggest bleeding and is a distinct hallmark of carcinosarcoma.6-7 Depending on the histopathologic assessment of the tumor (depth of invasion and presence or absence of metastases) and clinical presentation,8 the management of UCS requires a multimodality treatment comprised of surgery, systemic therapy, and radiotherapy. The estimated 5-year survival rate ranges from 33 to 39%, but the recurrence rate remains high.2,8 Figure 1 refers to a 61-year-old woman found dead in her flat, dressed in a sanitary napkin and a nightgown. Because the woman lived alone and had no family members, no health information could be achieved. An autopsy was performed to determine the cause of death. The body was in a good state of preservation; it weighed 85 kg and was 158 cm long (BMI = 34 Kg/m2 - Class I obesity). The sanitary napkin was smeared with a yellow-green-blackish creamy material upon external examination,. At dissection, both branches of the pulmonary artery trunk were occupied by red-brownish clots with multiple whitish streaks extending along the intraparenchymal course of the dividing branches of the pulmonary arteries (Figure 1A). They appeared to adhere tenaciously to the intimal surface, replicating the shape of the vascular lumen as a mold. All these characteristics were confirmed upon slicing, and a friable consistency was noted. On the abdominal incision, abundant yellow-green-blackish material of pasty consistency and purulent appearance was noted near the pelvic notch and between some intestinal loops. The uterus (longitudinal diameter = 18 cm, transversal = 11 cm, anteroposterior = 5 cm) appeared to be increased in volume, and the wall had a wall thickness of 1.5 cm. Inside the uterine cavity, a vegetative neoformation was detected (longitudinal diameter = 6 cm, transversal = 5 cm, anteroposterior = 4 cm), almost occluding the lumen. It was associated with abundant material resembling in color and consistency that was found in the abdomen. This neoformation adhered to the lateral walls and fundus of the uterus, extending almost to the cervix (Figure 1B). The ovaries were unscathed. Figure 1 A - Macroscopic view of lungs showing red-brownish clots in the pulmonary artery trunk extending along the intraparenchymal branches (scale bar= 8 cm); B - Macroscopic view of the uterus after dissection with a vegetative neoformation almost occluding its lumen, in association with abundant yellow-green-blackish material of pasty consistency (scale bar= 7 cm); C - Photomicrograph of the endometrial tumor with remnants of neoplastic glandular epithelial component and of residual glandular pseudo-lumen with multi-layered epithelium and cellular atypia (H&E, 200x); D - Photomicrograph of the endometrial tumor with sarcomatous component partly with fused cellularity, partly in the form of compact bundles with marked nuclear atypia and partly with a myxoid-like structure with foci arranged in bundles associated with a scattered cell neoplastic component (H&E; 100x).: Histopathologic examination of the mass revealed features of carcinosarcoma consisting almost entirely of a sarcomatous component and small foci of endometrioid- type adenocarcinoma, with neoplastic embolization of the intraparietal venous vessels. An inflammatory infiltrate associated with marked tumor necrosis was also noted (Figures 1C and 1D). With this background, the abdominal findings were interpreted as purulent discharge and necrosis following the adjoining uterine cancer. At the end of all investigations, the cause of death was identified as massive pulmonary arterial thrombosis in a subject with uterine carcinosarcoma. For completeness, we also considered peritonitis and sepsis as possible co-participation in the cause of death. However, we considered this hypothesis unlikely based on the macroscopic and microscopic findings. Specifically, the peritoneum, abdominal viscera, and serosa were shiny, without fibrinous deposits, and of normal consistency. The purulent-looking material appeared free and not adherent to the abdominal wall and intestinal loops, as would be the case with recent extravasation, and was not organized. The histologic findings confirmed these considerations, which revealed no evidence of septic embolism. Overall, there were no postmortem findings suggestive of peritonitis and sepsis. Had the massive and acutely fatal pulmonary arterial thrombosis not occurred, local or systemic septic complications most likely could have developed. The case was considered of interest because of the rare neoplasm, its size, and the very advanced stage of the disease. Another peculiarity was that one of the most lethal direct complications of this neoplasm, pulmonary arterial thrombosis, was observed. Unfortunately, the absence of family members and health information does not allow further clinical considerations, but the severity of the disease found is glaringly the result of neglected and untreated disease. This case demonstrates that such scenarios are still possible today, despite the increased importance of prevention campaigns. In this context, the observed anatomopathological findings are crucial as they enrich the knowledge of uterine carcinosarcoma, and their images may help forensic pathologists who have not previously encountered this rare disease

Surgical Margins Status Assessment After Breast Conserving Surgery: Is There a Difference Between Surgeon and Radiologist Evaluation?

Background: The aim of this study is to evaluate the accuracy of intra-operative specimen mammography (ISM) in surgical margins status assessment and highlight the concordance between the interpretations of the surgeon and the radiologist. Methods: Our cross-sectional study included 130 patients with early breast cancer, surgically treated between October 2013 and September 2017 in the multidisciplinary breast center of the A.O.U. City of Health and Science (which is a complex of several hospitals) in Turin, Italy. All recruited patients underwent breast conservative surgery. Surgical margins were evaluated intraoperatively, using intra-operative specimen mammography. A standard compression intra-operative specimen mammography was obtained by the surgeon using the dedicated radiological equipment (Faxitron®, BioVision). After the surgeon's evaluation of the margins, Faxitron images were sent to PACS. All ISMs images were analyzed by the same specialized radiologist in remote access to confirm the surgeon evaluation. We used kappa formula to report concordance. Results: The discordance rate of positive readings between the surgeon and the radiologist was 5.3% while that of negative readings was 6.9%. The concordance rate between radiologist and pathologist assessments was 100%. Intra-operative specimen mammography specificity was 94% (95% CI: 88–97), and sensitivity was 47% (95% CI: 38–56), with PPV found to be 53% (95% CI: 95% 44-62) and NPV determined to be 92% (95% CI: 86–96), when the assessment was made by the surgeon. Conclusion: Intra-operative specimen mammography is a helpful tool to identify infiltrated margins and to reduce the rate of secondary surgeries by recommending targeted re-excisions of corresponding orientations in order to obtain a final negative margin status. In our experience, not only radiologists but also surgeons could correctly read Faxitron® intra-operative specimen mammography

Anxiety, Depression, and Body Weight in Children and Adolescents With Migraine

Background: There is a lack of studies that explore the possible association between body weight, psychological symptoms, and migraine severity in pediatric populations. The purpose of the study was to explore: (1) the association between body weight and the frequency of migraine attacks, (2) the possible differences in anxiety and depression symptoms according to the frequency of attacks and body weight, and (3) the possible mediating role of anxiety and/or depression in the association between body weight and frequency of migraine attacks in children.Methods: One hundred and eleven children/adolescents with migraine were included (47 boys and 64 girls; mean age 11.7; +/- 2.4 years). The patients were classified as: (1) high frequency patients, reporting from weekly to daily episodes and (2) low frequency patients, with <= 3 episodes per month. According to their body mass index percentiles, the patients were divided in "Normal weight" (from >= 5 to <85 percentile), "Overweight" (from >= 85 to <95 percentile), and "Obese" (>= 95 percentile). Given the low number of obese patients, the overweight and obese groups were considered together in the "Overweight" group. Anxiety and depression symptoms were assessed by the Self-Administered Psychiatric Scales for Children and Adolescents (SAFA).Results: Fifty-four patients were normal in weight (49.6%), while 56 patients (50.4%) were overweight. The overweight patients showed a higher frequency of migraine attacks (64.7%; p < 0.05). Patients with a high frequency of attacks reported higher scores in all SAFA-Anxiety subscales (SAFA-A Tot: F = 15.107; p = 0.000). Overweight patients showed a significantly higher score in the "Separation anxiety" subscale (F = 7.855; p = 0.006). We found a mediating role between the overweight and high frequency for total anxiety (z = 2.11 +/- 0.03; p < 0.05) and social anxiety (z = 2.04 +/- 0.03; p < 0.05).Conclusions: Our results suggest that, among the children suffering from migraine, the overweight status is associated with a higher frequency of attacks and separation anxiety symptoms. In particular, our study provides the first evidence of the role of anxiety in linking overweight and the frequency of migraine attacks in children and adolescents

Imaging of hepatocellular carcinoma recurrence after liver transplantation

Liver transplantation (LT) provides the highest survival benefit to patients with unresectable hepatocellular carcinoma (HCC). The Milan criteria have been developed for the selection of LT candidates with the goal of improving survival and maintaining an acceptable risk of HCC recurrence. Despite this, recurrence of HCC after LT occurs in up to 20% of cases and represents a major concern due to the poor prognosis of these patients. Furthermore, several extended criteria for the selection of LT candidates have been proposed to account for the growing demand for organs and the resultant increase in the risk of HCC recurrence. Radiologists should be aware that HCC can recur after LT with multiple organ involvement. Knowledge of the location and radiologic appearance of recurrent HCC is necessary to ensure the choice of the most appropriate therapy. This paper aims to comprehensively summarize the spectrum of HCC recurrence after LT and to examine and discuss the imaging features of these lesions. CRITICAL RELEVANCE STATEMENT: This paper aims to share a review of imaging findings of HCC recurrence after LT and to make radiologists familiar with the spectrum of this disease

Pathophysiological Rationale and Clinical Evidence for Neurohormonal Modulation in Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome resulting from the interaction between cardiac diseases, comorbidities and ageing. HFpEF is characterised by the activation of neurohormonal axes, namely of the renin-angiotensin-aldosterone system and the sympathetic nervous system, although to a lesser extent compared with heart failure with reduced ejection fraction. This provides a rationale for neurohormonal modulation as a therapeutic approach for HFpEF. Nonetheless, randomised clinical trials have failed to demonstrate a prognostic benefit from neurohormonal modulation therapies in HFpEF, with the sole exception of patients with left ventricular ejection fraction in the lower range of normality, for whom the American guidelines suggest that such therapies may be considered. In this review, the pathophysiological rationale for neurohormonal modulation in HFpEF is summarised and the clinical evidence on pharmacological and nonpharmacological approaches backing current recommendations discussed

An osteochondral bio-engineered model to in vitro mimicking osteoarthritis

To date, treatments of Osteoarthritis are not able to provide the pathology regression. In vitro models are therefore necessary to: i) investigate the mechanisms involved in the disease evolution, ii) identify pharmacological targets, and iii) perform predictive tests for new drug delivery strategies

Eligibility for vericiguat in a real‐world, contemporary heart failure population

Aims: Vericiguat is a soluble guanylate cyclase stimulator and improves survival in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and an increased risk of decompensation. As real-world data on how many patients could be eligible for vericiguat therapy derive from outdated registries, we aimed to assess eligibility in a prospective cohort of patients with HF. Methods and results: Data from consecutive HF patients undergoing an elective ambulatory visit at five university hospitals from 3 July to 28 July 2023 were collected. Independent investigators assessed which patients (i) met the eligibility criteria of the VICTORIA trial, (ii) complied with HF guideline recommendations, (iii) met regulatory agency criteria, or (iv) met criteria for refundability according to the Italian regulatory agency. Patients (n = 346, 72% men, median age 69 years) had HFrEF in 57% of cases, left ventricular ejection fraction < 45% in 68%, and New York Heart Association class II-IV symptoms in 76%. Patients meeting the eligibility criteria of the VICTORIA trial or European and American HF Guideline recommendations were 9% and 13%, respectively. Patients meeting Food and Drug Administration (FDA) or European Medicines Agency (EMA) label criteria were 19% and 17%, respectively. Drug costs would be covered by the Italian National Health System in 10% of patients [if a sodium-glucose cotransporter-2 inhibitor (SGLT2i) is not mandatory] or in 8% (if an SGLT2i is requested). Conclusions: In a real-world study, 9% of patients met the eligibility criteria of the VICTORIA trial, but up to 13% complied with guideline recommendations and up to 19% met FDA or EMA criteria. In Italy, drug costs would be covered by up to 10% of patients