Hepatic Arterial Buffer Response: Pathologic Evidence in Non-Cirrhotic Human Liver with Portal Vein Thrombosis

poster abstractHepatic arterial buffer response (HABR) is the ability of the hepatic artery (HA) to compensate for changes in portal flow. Experimentally, occlusion of the portal vein leads to compensatory increase in HA flow with minimal parenchymal effects. Wether portal vein thrombosis (PVT) causes similar effects in the human liver is unknown. This study aims to answer this question as well as elucidate any microscopic features that may reliably assist diagnosis of PVT in the non-cirrhotic liver. We studied patients with PVT and no concomitant liver pathology. Age and gender matched livers with normal morphology served as controls. Following parameters were graded as subtle or obvious and focal or diffuse in a blinded fashion: sinusoidal dilatation, central and portal vein (PV) dilatation, PV absence, hepatic plate thinning and thickening. Outer and luminal diameters and wall thickness of HA, and outer diameter of accompanying bile ducts (BD) were measured. There were 16 patients (8 men, 8 women; mean age, 46.5 years) who presented with varices (12), ascites (8) and splenomegaly (11). Subtle and or focal dilatations of CV, PV and sinusoids as well as thinning/thickening of hepatic plates were common findings in both groups but were diffuse and obvious predominantly in cases of PVT. Absence or attenuation of PV was seen only in cases of PVT. The large HA were dilated in resection specimens of patients with PVT, p<0.05. This difference was not seen in biopsy specimens. There was no difference in the small HA in either biopsy or resection specimens or other measurements of HA or BD. In conclusion, septal branches of the HA dilate as a compensatory response to long standing thrombosis. Microscopic features of PVT are subtle but when obvious and/or diffuse in a patient with non-cirrhotic portal hypertension should raise suspicion for this diagnosis

Hypertrophic pulmonary osteoarthropathy, secretory diarrhea and pancoast syndrome in the setting of a large cell neuroendocrine carcinoma of the lung: A case report

Large cell neuroendocrine carcinoma of the lung is a rare and aggressive pulmonary malignancy. Given its peripheral location, patients are frequently asymptomatic at the time of diagnosis or present with non-specific complaints. Moreover, its association with paraneoplastic syndromes or structural intrathoracic complications are highly atypical. Here, we report a case involving a 57-year-old female who presented with two simultaneous paraneoplastic syndromes, including hypertrophic pulmonary osteoarthropathy and secretory diarrhea, prior to the diagnosis of an early-stage large cell neuroendocrine carcinoma of the lung. Both syndromes showcased rapid symptomatic resolution following tumor resection. Upon disease recurrence, the patient developed a presentation consistent with Pancoast syndrome, with gradual improvement following the initiation of chemoradiotherapy. Individually, these conditions are rarely reported in association with large cell neuroendocrine carcinoma of the lung making their combination highly unusual. Furthermore, related symptoms were present both before and at the time of diagnosis, and upon disease recurrence. This highlights the importance of maintaining a high clinical suspicion for atypical manifestations of malignancy

Myeloid sarcoma of the prostate revealed by urinary retention: a case report

Myeloid sarcoma (MS) of the prostate is very uncommon with only 17 reported cases in the literature. Here, a singular case of a MS of the prostate discovered through investigations for urinary retention and revealing an acute leukaemia classified as an acute myeloid leukaemia (AML) with inversion 16 (inv16) according to the World Health Organization (WHO) classification (AML-M4 with inv16 in the French–American–British (FAB) classification) in a 65-year-old man is presented. None of the previously reported and reviewed cases of prostatic MS were of AML-M4 type. Moreover, a translocation t(3;7) was identified in our case. Such a translocation was recently described in some acute myeloid processes. MS treatment consists of combining surgical intervention and chemotherapy. Radiation therapy could be beneficial for the localised disease of the prostate. Allogenic haematopoietic stem cell transplantation is also a promising therapy for MS

Malignant Peritoneal Mesothelioma in the setting of a Ventriculo-Peritoneal Shunt: A novel clinical presentation

We report a case of malignant peritoneal mesothelioma (MPM) in a 31-year-old male with history of cerebral palsy, hydrocephalus, and ventriculoperitoneal shunt (VPS) placed since infancy. He presented with fever, abdominal pain and distension. Computed tomography scan revealed a thick-walled rim-enhancing fluid collection, interpreted as pseudocyst. Intraoperatively, diffuse nodular peritoneal thickening with adhesions was demonstrated. The resection specimen consisted of multiple membranous fragments displaying firm nodules. Microscopic examination revealed a tumefactive malignant-appearing epithelioid proliferation involving the peritoneum, focally invading the underlying fat. Immunohistochemically, the tumor cells expressed keratin AE1/AE3, CK7, CK5/6, Calretinin, WT1 and D2-40, and were negative for CEA and MOC31. The findings were consistent with MPM, epithelioid type. The patient’s condition continued to decline with increasing abdominal distension during the month following the original diagnosis. While atypical mesothelial hyperplasia has been described in association with long standing VPS, well-documented cases of MPM have not been previously reported in such context

Ablation of PDE4B protects from Pseudomonas aeruginosa-induced acute lung injury in mice by ameliorating the cytostorm and associated hypothermia

Pseudomonas aeruginosa is a frequent cause of hospital-acquired lung infections characterized by hyperinflammation, antibiotic resistance, and high morbidity/mortality. Here, we show that the genetic ablation of one cAMP-phosphodiesterase 4 subtype, PDE4B, is sufficient to protect mice from acute lung injury induced by P aeruginosa infection as it reduces pulmonary and systemic levels of pro-inflammatory cytokines, as well as pulmonary vascular leakage and mortality. Surprisingly, despite dampening immune responses, bacterial clearance in the lungs of PDE4B-KO mice is significantly improved compared to WT controls. In wildtypes, P aeruginosa-infection produces high systemic levels of several cytokines, including TNF-α, IL-1β, and IL-6, that act as cryogens and render the animals hypothermic. This, in turn, diminishes their ability to clear the bacteria. Ablation of PDE4B curbs both the initial production of acute response cytokines, including TNF-α and IL-1β, as well as their downstream signaling, specifically the induction of the secondary-response cytokine IL-6. This synergistic action protects PDE4B-KO mice from the deleterious effects of the P aeruginosa-induced cytostorm, while concurrently improving bacterial clearance, rather than being immunosuppressive. These benefits of PDE4B ablation are in contrast to the effects resulting from treatment with PAN-PDE4 inhibitors, which have been shown to increase bacterial burden and dissemination. Thus, PDE4B represents a promising therapeutic target in settings of P aeruginosa lung infections