Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Retinal projections to the lateral posterior-pulvinar complex in intact and early visual cortex lesioned cats

In intact cats, it is generally considered that the lateral posterior-pulvinar complex (LP-pulvinar) does not receive direct retinal terminals, with the exception of the retino-recipient zone known as the geniculate wing. There is, however, some evidence that early lesions of the visual cortex can occasionally induce the formation of novel retinal projections to the LP nucleus. Given the importance of knowing the connectivity pattern of the LP-pulvinar complex in intact and lesioned animals, we used the B fragment of cholera toxin, a sensitive anterograde tracer, to reinvestigate the retinal projections to the LP-pulvinar in normal cats and in cats with early unilateral lesions of the visual cortex (areas 17 and 18). Immunohistochemical localization of the toxin was performed to show the distribution and morphology of retinofugal terminals. A direct bilateral but predominantly contralateral retinal projection reached the caudal portion of LPl and LPm in the form of patches located mainly along its dorsomedial surface and many scattered terminals. The distribution of retinal projections to LP-pulvinar in intact and operated cats did not differ. Contrary to what had been previously reported, we found no evidence for lesion-induced sprouting of retinal axons in these higher-order thalamic nuclei. Retinal input to the LP-pulvinar might modulate visual responses driven by primary visual cortex or superior colliculus.     

Subchondroplasty in the treatment of bone Marrow lesion in early Knee Osteoarthritis: A systematic review of clinical and radiological outcomes

BackgroundKnee osteoarthritis (KOA) is increasingly prevalent in North American society. The significant societal burden it represents makes it essential to promote and target new treatments in earlier phases of the disease. Among others, subchondroplasty is a newly documented technique using calcium phosphate injection targeting the osteochondral lesions preceding KOA, also known as Bone Marrow Lesions (BMLs). This article aimed to review the existing literature on clinical and radiological outcomes of subchondroplasty in the treatment of BMLs in KOA.MethodA systematic review was performed using PubMed, Embase, Medline and Cochrane Database of Systematic Reviews. Studies on calcium phosphate injections into BMLs for KOA and its clinical and radiological outcomes were screened and reviewed by independent evaluators.ResultsAfter screening, ten articles were included, totaling 540 patients. Follow-up ranged from 6 months to 7 years. Overall, the procedure showed significant functional and quality of life improvement, as well as pain relief, as shown by Patients-Reported Outcomes Measures (PROMs). There were very few complications reported, the most important being leakage of calcium phosphate outside the targeted site. Conversion rate to total knee arthroplasty (TKA) ranged from 14 % to 30 % at 2 years post-procedure. Long term radiological outcomes have been poorly documented.ConclusionsSubchondroplasty is a promising avenue for the treatment of KOA. However, quality evidence is still required before any real conclusions and practical management guidelines can be drawn. Prospective, randomized studies with a control group and a rigorous assessment of long-term clinical and radiological outcomes are recommended.     

Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions

von Hippel-Lindau (VHL) disease arises from mutations in the VHL gene and predisposes patients to develop a variety of tumors in different organs. In the kidney, single or multiple cysts and renal cell carcinomas (RCC) may occur. Both inter- and intrafamilial heterogeneity in clinical expression are well recognized. To identify VHL-dependent genetic factors, we investigated the renal phenotype in 274 individuals from 126 unrelated VHL families in whom 92 different VHL mutations were characterized. The incidence of renal involvement was increased in families with mutations leading to truncated protein (MLTP) or large rearrangement, as compared to families with missense changes (81 vs. 63%, respectively; P=0.03). In the latter group, we identified two mutation cluster regions (MCRs) associated with a high risk of harboring renal lesions: MCR-1 (codons 74-90) and MCR-2 (codons 130-136). In addition, the incidence of RCC was higher in families with MLTP than in families with missense changes (75 vs. 57%; P=0.04). Furthermore, mutations within MCR-1 but not MCR-2 conferred genetic susceptibility to develop RCC. Overall, our data argued for a substantial contribution of the genetic change in the VHL gene to susceptibility to renal phenotype in VHL patients.     

PIGQ glycosylphosphatidylinositol‐anchored protein deficiency: Characterizing the phenotype

PIGQ (OMIM *605754) encodes phosphatidylinositol glycan biosynthesis class Q (PIGQ) and is required for proper functioning of an N‐acetylglucosamine transferase complex in a similar manner to the more established PIGA, PIGC, and PIGH. There are two previous patients reported with homozygous and apparently deleterious PIGQ mutations. Here, we provide the first detailed clinical report of a patient with heterozygous deleterious mutations associated with glycosylphosphatidylinositol‐anchored protein (GPI‐AP) biosynthesis deficiency. Our patient died at 10 months of age. The rare skeletal findings in this disorder expand the differential diagnosis of long bone radiolucent lesions and sphenoid wing dysplasia. This clinical report describes a new and rare disorder—PIGQ GPI‐AP biosynthesis deficiency syndrome.     

Initiation of mouse-killing behavior following amygdaloid lesions in the rat(author's transl)]

Long-Evans hooded rats were tested for emotionality and observed by pairs in an open field for 6 consecutive days. Postoperative observations indicated that both emotionality and social cohesiveness were dramatically altered by ventromedial and anterolateral hypothalamic lesions. Tegmental, interpeduncular and habenular lesions were shown to have no effect on these behaviors. Alterations in behavior observed following hypothalamic ablations were related to septal and amygdaloid effects, and the possibility of separate projection systems for emotionality and social cohesiveness was discussed.     

Enhanced responsiveness of human extravisual areas to photic stimulation in patients with severely reduced vision

Lesions in the primary visual cortex induce severe loss of visual perception. Depending on the size of the lesion, the visual field might be affected by small scotomas, hemianopia, or complete loss of vision (cortical blindness). In many cases, the whole visual field of the patient is affected by the lesion, but diffuse light-dark discrimination remains (residual rudimentary vision, RRV). In other cases, a sparing of a few degrees can be found (severely reduced vision, SRV).In a follow-up study, we mapped visually induced cerebral activation of three subjects with SRV using functional magnetic resonance imaging. We were especially interested in the visual areas that would be activated if subjects could perceive the stimulus consciously although information flow from V1 to higher visual areas was strongly reduced or virtually absent. Because subjects were only able to discriminate strong light from darkness, we used goggles flashing intense red light at a frequency of 3 Hz for full visual field stimulation. Besides reduced activation in V1, we found activation in the parietal cortex, the frontal eye fields (FEF), and the supplementary eye fields (SEF). In all patients, FEF activation was pronounced in the right hemisphere. These patterns were never seen in healthy volunteers. In a patient who recovered completely, we observed that extrastriate activation disappeared in parallel with the visual field restitution. This result suggests that damage to the primary visual cortex changes the responsiveness of parietal and extravisual frontal areas in patients with SRV. This unexpected result might be explained by increased stimulus-related activation of attention-related networks.     

An Autopsy Case of Metastatic Foci of Hepatocellular Carcinoma in Adenomatous Hyperplasias of the Liver

Adenomatous hyperplasia of the liver is known as a preneoplastic or early developmental stage of hepatocellular carcinoma, in which overt malignant foci occasionally develop. We have recently experienced an autopsy case (a 70-year-old male) of liver cirrhosis with hepatocellular carcinoma and two nodules of adenomatous hyperplasia. The latter two nodules contained several microscopic foci of moderately differentiated hepatocellular carcinoma. There were a number of tumor microemboli in portal vein branches within areas of adenomatous hyperplasia in addition to areas surrounding cirrhotic liver, some of which grew into the parenchyma of adenomatous hyperplasia and cirrhotic regenerative nodules. These findings and the fact that adenomatous hyperplasia contained portal tracts including portal venous branches, suggest that malignant foci in adenomatous hyperplasia of the liver in this case might represent metastases from hepatocellular carcinoma in other parts of the liver via the intrahepatic portal venous system. Acta Pathol Jpn 41: 911 915, 1991.     

Renal cell adenomas and carcinomas in hemodialysis patients: Relationship between hemodialysis period and development of lesions

Step-sections of 96 whole kidneys from 50 chronic hemodialysis patients were subjected to a histopathological and quantitative investigation with regard to the development of renal neoplastic lesions. The range of hemodialysis duration was from 1 to 222 months. A total of 349 renal cell adenomas were found in 41 cases (82%). They were commonly multiple and present bilaterally. Renal cell carcinomas were evident in four cases (8%), with hemodialysis durations of 54, 57, 112 and 222 months. The incidence of adenomas increased in a hemodialysis duration-dependent manner, indicating a high risk of renal cell tumor development in chronic hemodialysis patients. Furthermore, acquired cystic disease of the kidney (ACDK) was also observed in 12 cases (24.0%), where the mean hemodialysis period was 143.4 ± 48.0 months. This value was significantly longer than that of non-ACDK cases (P < 0.001). There was, however, no clear relationship between the appearance of ACDK and renal cell tumors. The present results underline the necessity for attention to possible neoplasia of the kidney in patients on long-term hemodialysis.     

Clinical significance of suprascapular nerve mobilization

The anatomy of the suprascapular nerve is important to surgeons when focal nerve lesions necessitate surgical repair. Recent experience with a patient who had a complete suprascapular nerve lesion in the retroclavicular region (combined with axillary and musculocutaneous nerve lesions) is presented to illustrate that successful direct nerve repair is possible despite resection of a neuroma. Specifically, we found that neurolysis and mobilization of the suprascapular nerve and release of the superior transverse scapular ligament provided the necessary nerve length to achieve direct nerve repair after the neuroma was removed. A combined supraclavicular and infraclavicular approach to the suprascapular nerve provided excellent visualization, especially in the retroclavicular region. Postoperatively, the patient recovered complete shoulder abduction and external rotation with the direct repair, an outcome uncommonly achieved with interpositional grafting. Based on our operative experience, we set out to quantify the length that the suprascapular nerve could be mobilized with neurolysis. Mobilization of the nerve and release of the superior transverse scapular ligament generated an average of 1.6 cm and 0.7 cm of extra nerve length respectively, totaling 2.3 cm of additional usable nerve length overall. The ability to expose the suprascapular nerve in the retroclavicular/infraclavicular region and to mobilize the suprascapular nerve for possible direct repair has not been previously emphasized and is clinically important. This surgical approach and technique permits direct nerve repair after resection of a focal neuroma in the retroclavicular or infraclavicular region, thus avoiding interpositional grafting, and improving outcomes.