Association of Large Vessel Aneurysm/Pseudo-Aneurysm/Aortitis and Deep Vein Thrombosis in Patients with Behçet’s Disease: A Case Report

Background: Behçet’s disease (BD) is a complex vasculitis with some vascular manifestations including venous thrombosis, arterial thrombosis/aneurysm/pseudoaneurysm, and co-associated venous thrombosis and arterial lesions. We present two patients with Behçet’s disease came with progressive both arterial and venous involvement. Case Presentation: The first patient was a young man with recurrent oral aphthosis and skin folliculitis and referred with complaint of new abdominal pain and 2 months severe headache. He had not referred to a physician due to COVID-19 pandemic until that time. In addition, he gradually developed a lower extremity edema and eventually was diagnosed with BD complicated with brain sagittal sinus vein thrombosis, abdominal aortic aneurysms and aortitis and deep vein thrombosis (DVT) of femoral vein. The second patient was a young woman with previous history of uveitis, DVT and recurrent oral and genital aphthosis presented with a large inguinal mass due to large iliac artery pseudoaneurysm impending to rupture, and after the operation, due to poor follow-up, developed a new femoral DVT. Conclusion: It seems the same inflammatory process is responsible for arterial and venous involvement in patients with BD, so it should be considered that involvement in one side (venous/arterial) can be a risk factor for the other side (venous/arterial) and early immunosuppressive treatment should always be considered to improve the prognosis.

Total neoadjuvant FOLFIRINOX or gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2): A nationwide multicenter randomized controlled trial.

TPS4171 Background: Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials (including the Dutch PREOPANC trial) have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including gemcitabine-based chemoradiotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether total neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine (i.e. the intervention arm of the PREOPANC trial) in patients with resectable or borderline resectable pancreatic cancer. Methods: This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) added during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients, assuming an accrual period of 3 years and 1.5 years follow-up. Between June 2018 and January 2021, 375 patients were enrolled in 20 centers in the Netherlands and accrual is complete. Final analyses are expected at the end of 2022. Netherlands Trial Register: NL7094. Clinical trial information: NL7094.

The pattern of cardiovascular manifestations in Egyptian Behçet’s patients and its relation to disease activity

Background Behçet’s disease (BD) is also referred to as vascular BD when it frequently involves the heart and vessels. This study aimed to describe the cardiovascular manifestations in patients with BD and its correlation to disease activity. We conducted a cross-sectional study on 40 patients diagnosed with BD according to the International Criteria for Behçet’s Disease 2014. All the patients were subjected to detailed history taking, full clinical examination, lab investigations, resting electrocardiogram, trans-thoracic echocardiography, and carotid artery duplex for measuring intimal thickness, peripheral arterial and venous duplex, computed tomography pulmonary angiography, and full ophthalmological examination. Regarding the activity of the disease, it was assessed according to the score of Behçet’s Disease Current Activity Form (BDCAF). Results The most common cardiac manifestation was valvular lesion (67.5%) where the most frequently affected valve was the tricuspid valve (27.5%). Although 25% of patients had left ventricular diastolic dysfunction, only 5% had intracardiac masses. Approximately 52.5% of patients had vascular lesion (deep venous thrombosis 45%, arterial involvement 7.5% [as pulmonary artery thrombosis 5% and aneurysm 2.5%]). Increase in intima media thickness (IMT) was observed in 7.5% of patients, while 60% had abnormal lipid profiles. Hypercholesterolemia was the most common lipid abnormality (50%). BDCAF score range was 4–12, which was significantly correlated to multiple cardiovascular parameters as a mitral, tricuspid valve, and vascular venous involvement (p < 0.05), while not significantly correlated to lipid profile (p > 0.05). Conclusion Cardiovascular complications are frequent among patients with BD, even those who are asymptomatic; therefore, these complications must be screened for early detection and proper management.

An Overview of Venous Abnormalities Related to the Development of Lesions in Multiple Sclerosis

The etiology of multiple sclerosis (MS) is currently understood to be autoimmune. However, there is a long history and growing evidence for disrupted vasculature and flow within the disease pathology. A broad review of the literature related to vascular effects in MS revealed a suggestive role for abnormal flow in the medullary vein system. Evidence for venous involvement in multiple sclerosis dates back to the early pathological work by Charcot and Bourneville, in the mid-nineteenth century. Pioneering work by Adams in the 1980s demonstrated vasculitis within the walls of veins and venules proximal to active MS lesions. And more recently, magnetic resonance imaging (MRI) has been used to show manifestations of the central vein as a precursor to the development of new MS lesions, and high-resolution MRI using Ferumoxytol has been used to reveal the microvasculature that has previously only been demonstrated in cadaver brains. Both approaches may shed new light into the structural changes occurring in MS lesions. The material covered in this review shows that multiple pathophysiological events may occur sequentially, in parallel, or in a vicious circle which include: endothelial damage, venous collagenosis and fibrin deposition, loss of vessel compliance, venous hypertension, perfusion reduction followed by ischemia, medullary vein dilation and local vascular remodeling. We come to the conclusion that a potential source of MS lesions is due to locally disrupted flow which in turn leads to remodeling of the medullary veins followed by endothelial damage with the subsequent escape of glial cells, cytokines, etc. These ultimately lead to the cascade of inflammatory and demyelinating events which ensue in the course of the disease.

Cribriform colon cancer: a morphological growth pattern associated with extramural venous invasion, nodal metastases and microsatellite stability

BackgroundCribriform comedo-type adenocarcinoma was a colon cancer subtype recognised in the previous WHO classification of tumours that is no longer included in the recent edition. Previous reports have described colon cancers with cribriform growth as having worse overall survival and being associated with microsatellite stability. We sought to validate whether cribriform carcinoma (CC) is a distinct morphological subtype with clinical relevance in the context of modern colon cancer diagnosis.MethodsConsecutive cases of non-neoadjuvantly treated colon cancer resections were identified (n=177) and reviewed to evaluate for CC and other histopathological and clinical features. CC was defined as solid nests of cancer with round, ‘punched out’ spaces and intraluminal bridges, reminiscent of ductal carcinoma in situ of the breast.ResultsCC was present in 18.6% of the consecutive case cohort. Compared with all other cases, CC was associated with positive lymph nodes, increased depth of invasion, extramural venous involvement (EMVI), and microsatellite stability, and was less likely to have tumour infiltrating lymphocytes (p<0.05). In contrast to previous reports, we did not find significantly worse overall, disease-specific or recurrence-free survival for CC. Morphological features mimicking CC occurred in 33.3% of all other colon cancer cases.ConclusionIdentifying CC may be useful due to its association with worse stage at presentation and EMVI, but given that cribriform-like appearance may be found in many colon cancer cases and that we did not find a survival difference for CC, CC may not necessitate its own subtype classification.

Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial

Background Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients. Methods This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up. Discussion The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer. Trial registration Primary registry and trial identifying number: EudraCT: 2017–002036-17. Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register – NL7094, NL61961.078.17, MEC-2018-004.

COMPARATIVE STUDY OF LIPID PROFILE BETWEEN ISCHEMIC AND HAEMORRHAGIC STROKE AT MEDICINE DEPARTMENT OF JLNMCH, BHAGALPUR, BIHAR

Background: Stroke is one of the major global health problems. Stroke is the most common clinical manifestation of cerebrovascular disease of which more than 99% are due to arterial involvement and less than 1% due to venous involvement in the form of Cerebral Venous Thrombosis (CVT). Among arterial causes 85% are due to infarction and 15% due to haemorrhage. There is difference in serum lipid levels in subtypes of strokes to guide lipid-lowering therapy which can reduce incidence of stroke and stroke related mortality by adapting primary and secondary preventive measures. Authors have endeavoured to correlate severity of lipid derangement and stroke. Methods: In this study 64 consecutive eligible ischaemic stroke cases and 64 eligible hemorrhagic stroke cases would be included. Cases of strokes will be divided into ischaemic and hemorrhagic as per clinical features and with help of brain imaging by CT scan and MRI at the time of admission and 8 hour fasting lipid profile was collected from all cases. All this information will be filled in preformed format. Results: Serum lipid profile of two categories of stroke showed raised serum total cholesterol in 39.1% patients of ischaemic stroke in contrast to 18.8% patients with haemorrhagic stroke (p=0.019). Stroke patients showed raised in LDL cholesterol in 29.7% patients of ischaemic stroke in contrast to 9.4% patients with haemorrhagic stroke, (p=0.007). Conclusions: Based on the finding of our study we conclude that ischemic stroke patient had higher lipid derangement as compare to haemorrhagic stroke in terms of raise total cholesterol, LDL cholesterol and decrease HDL cholesterol.