Colorectal cancer in the young - outcomes following surgical management?

INTRODUCTION: Colorectal cancer (CRC) is the third most common cancer, accounting for approximately 10% of all cancer deaths. The incidence of CRC in young adults and the adolescent population is increasing. This study aims to highlight short-term outcomes for young patients with CRC. METHODS: Data were collected retrospectively for all patients aged less than 50 years diagnosed with CRC at a university teaching hospital between October 2012 and June 2018. The primary endpoints were disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 120 patients (65 males, 55 females) with CRC aged under 50 years were initially included; 20 did not receive surgical treatment (12 metastatic adenocarcinoma, 5 metastatic squamous cell cancer (SCC), 3 neuroendocrine tumours (NET)), and 13 patients had insufficient data for analysis and were excluded. A total of 87 patients underwent surgical intervention and 66 with diagnosis of adenocarcinoma were included in survival analysis. Median age of patients was 42 years (19-49 years). Cancer recurrence was seen in 14 patients, 10 showing local, 3 liver and 1 lung metastasis. The median OS was 28 months (3-156 months). The median DFS was 13 months (3-85 months). Overall 5-year survival and DFS were 72% and 59%, respectively. Median survival in the group who did not undergo surgery was 4.5 months (1-15 months). CONCLUSIONS: CRC is often more advanced and aggressive in younger patients. Current guidelines can result in young patients being investigated/treated for other gastrointestinal conditions before referral for CRC investigation.

Immunosuppressive human anti-CD83 monoclonal antibody depletion of activated dendritic cells in transplantation.

Current immunosuppressive/anti-inflammatory agents target the responding effector arm of the immune response and their nonspecific action increases the risk of infection and malignancy. These effects impact on their use in allogeneic haematopoietic cell transplantation and other forms of transplantation. Interventions that target activated dendritic cells (DCs) have the potential to suppress the induction of undesired immune responses (for example, graft versus host disease (GVHD) or transplant rejection) and to leave protective T-cell immune responses intact (for example, cytomegalovirus (CMV) immunity). We developed a human IgG1 monoclonal antibody (mAb), 3C12, specific for CD83, which is expressed on activated but not resting DC. The 3C12 mAb and an affinity improved version, 3C12C, depleted CD83(+) cells by CD16(+) NK cell-mediated antibody-dependent cellular cytotoxicity, and inhibited allogeneic T-cell proliferation in vitro. A single dose of 3C12C prevented human peripheral blood mononuclear cell-induced acute GVHD in SCID mouse recipients. The mAb 3C12C depleted CMRF-44(+)CD83(bright) activated DC but spared CD83(dim/-) DC in vivo. It reduced human T-cell activation in vivo and maintained the proportion of CD4(+) FoxP3(+) CD25(+) Treg cells and also viral-specific CD8(+) T cells. The anti-CD83 mAb, 3C12C, merits further evaluation as a new immunosuppressive agent in transplantation.

RNA trafficking signals in human immunodeficiency virus type 1.

Intracellular trafficking of retroviral RNAs is a potential mechanism to target viral gene expression to specific regions of infected cells. Here we show that the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized extensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2 dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the same RNA trafficking granules and are cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in targeting HIV gene expression is discussed.

Binding of an RNA trafficking response element to heterogeneous nuclear ribonucleoproteins A1 and A2.

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 binds a 21-nucleotide myelin basic protein mRNA response element, the A2RE, and A2RE-like sequences in other localized mRNAs, and is a trans-acting factor in oligodendrocyte cytoplasmic RNA trafficking. Recombinant human hnRNPs A1 and A2 were used in a biosensor to explore interactions with A2RE and the cognate oligodeoxyribonucleotide. Both proteins have a single site that bound oligonucleotides with markedly different sequences but did not bind in the presence of heparin. Both also possess a second, specific site that bound only A2RE and was unaffected by heparin. hnRNP A2 bound A2RE in the latter site with a K(d) near 50 nm, whereas the K(d) for hnRNP A1 was above 10 microm. UV cross-linking assays led to a similar conclusion. Mutant A2RE sequences, that in earlier qualitative studies appeared not to bind hnRNP A2 or support RNA trafficking in oligodendrocytes, had dissociation constants above 5 microm for this protein. The two concatenated RNA recognition motifs (RRMs), but not the individual RRMs, mimicked the binding behavior of hnRNP A2. These data highlight the specificity of the interaction of A2RE with these hnRNPs and suggest that the sequence-specific A2RE-binding site on hnRNP A2 is formed by both RRMs acting in cis.

Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking.

Cytoplasmic transport and localization of mRNA has been reported for a range of oocytes and somatic cells. The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 response element (A2RE) is a 21-nucleotide segment of the myelin basic protein mRNA that is necessary and sufficient for cytoplasmic transport of this message in oligodendrocytes. The predominant A2RE-binding protein in rat brain has previously been identified as hnRNP A2. Here we report that an 11-nucleotide subsegment of the A2RE (A2RE11) was as effective as the full-length A2RE in binding hnRNP A2 and mediating transport of heterologous RNA in oligodendrocytes. Point mutations of the A2RE11 that eliminated binding to hnRNP A2 also markedly reduced the ability of these oligoribonucleotides to support RNA transport. Oligodendrocytes treated with antisense oligonucleotides directed against the translation start site of hnRNP A2 had reduced levels of this protein and disrupted transport of microinjected myelin basic protein RNA. Several A2RE-like sequences from localized neuronal RNAs also bound hnRNP A2 and promoted RNA transport in oligodendrocytes. These data demonstrate the specificity of A2RE recognition by hnRNP A2, provide direct evidence for the involvement of hnRNP A2 in cytoplasmic RNA transport, and suggest that this protein may interact with a wide variety of localized messages that possess A2RE-like sequences.

Prediction of neonatal alloimmune thrombocytopenia using PCR.

Neonatal alloimmune thrombocytopenia (NAIT) is a potentially fatal condition and in the majority of cases is associated with maternal antibodies to the HPA-1a (PLA1) haplotype. Early diagnosis in utero can enhance survival rates. The application of DNA genomic analysis and PCR technology for the determination of the HPA-1a/HPA-1b (PLA1/PLA2) locus is described and applied in a family study where the fetus was diagnosed to have NAIT. This rapid technique differentiated between the 3 haplotypes HPA-1a/HPA-1a, HPA-1b/HPA-1b and HPA-1a/HPA-1b using the polymorphism at base 196 of the GPIIIa gene. This is the first Australian report on the establishment of this technology for platelet genotype typing and the application in the diagnosis of NAIT. This technique can be performed on DNA extracted from any nucleated cells and avoids the difficulty of requiring fetal platelets for serological typing when NAIT is suspected. The PCR technique of genomic DNA analysis has an important application in the prediction and management of this potentially severe condition.

Occult posttraumatic osteochondral lesions of the knee: prevalence, classification, and short-term sequelae evaluated with MR imaging.

The prevalence, characterization, and classification of acute, post-traumatic, occult subcortical fractures of the knee, identified at magnetic resonance (MR) imaging, were evaluated prospectively in 120 consecutive patients first seen with acute posttraumatic hemarthrosis of the knee. Occult subcortical femoral and tibial fractures were identified in 72% of patients. A modified MR imaging classification is suggested based on a combination of the appearances of such lesions at MR imaging and their short-term osteochondral sequelae. Among 67% of a cohort of 21 patients first seen with what have been described as occult geographic subcortical fractures, osteochondral sequelae were seen at follow-up MR imaging 6-12 months later. The evidence from this study indicates that specific subcategories of occult subcortical knee fractures are associated with an inordinately high prevalence of osteochondral sequelae, especially significant cartilage damage.

The film-reporting session as a qualifying examination in diagnostic radiology.

To assess the value of a film-reporting session as a qualifying examination in radiology, 11 residents were allowed 1 hour to interpret and dictate reports on 20 test cases. Reports were marked by four examiners; two used a standardized marking scheme and two a simple pass or fail assessment. The marking schemes were compared and the scores were related to the level of training and performance on the American College of Radiology (ACR) practice examination. With pass or fail marking, there was 55% agreement between markers and poor correlation with the candidates' training level. There was 100% marker agreement using the standardized scheme and better correlation with the level of training. There was poor correlation with the ACR scores. Preliminary results suggest that a film-reporting session with standardized marking is feasible and may be a useful addition to current evaluation methods in diagnostic radiology.

Destructive joint disease following replantation of digits of the hand.

Microsurgical techniques now often allow the repair of severed digits. After noticing destructive joint changes in a patient who underwent such repair, the authors examined the postoperative radiographs of 27 other patients who underwent repair of severed digits at the University Hospital, London, Ontario, between 1984 and 1987. They found five patients who were similarly affected. The mechanism of destruction is not known, but the authors believe that osteonecrosis plays a role or that the cause may be neurovascular.

Anteroposterior radiographs of the osteoarthritic knee.

Destruction of the articular cartilage is the first change seen on gross examination of the knee in osteoarthritis. Weight-bearing radiographs are conventionally taken with the knee in full extension. Biomechanical studies have shown, however, that the major contact stresses in the femorotibial articulation occur when the knee is flexed about 28 degrees. Arthroscopy has confirmed that cartilage loss occurs in a more posterior portion of the femoral condyles than is revealed by radiographs taken in full extension. The 'standing tunnel view' is a weight-bearing postero-anterior radiograph taken with the knee in 30 degrees of flexion. The radiographs of 64 patients have been used to compare the conventional with the standing tunnel view. In 10 knees in which the conventional view suggested normal cartilage the standing tunnel view revealed severe degeneration.

Fractures of the base of the fifth metatarsal.

In 1902 Sir Robert Jones described a fracture of the fifth metatarsal which he incurred while dancing. Since that time, fractures of the base of the fifth metatarsal have been called "Jones fractures". Fractures of the tuberosity at the base of the fifth metatarsal are common and usually respond readily to conservative treatment. Less frequently the fracture occurs more distally through the proximal metaphysis. Eleven patients with fractures of the proximal metaphysis were reviewed to determine if they represented a clinically distinct subgroup. Seven of the patients were men between 19 and 25 years of age who fractured the fifth metatarsal playing sports. The fractures were slow to heal and one required internal fixation with bone grafting. Fractures of the proximal metaphysis of the fifth metatarsal have a different mechanism of injury and a less favourable prognosis than do tuberosity fractures. When they occur in young athletes, more aggressive treatment is required.

Radiology seminars using teaching kits.

Clinico-radiological seminars are an effective method of teaching medical students. However, in busy departments it is often difficult to provide enough radiologists for small group instruction. This can be facilitated by the use of prepared teaching kits. Each kit contains a set of duplicated films and a syllabus which gives a short clinical history for each patient and a series of questions to be used to direct the discussion. Each diagnostic problem is chosen to demonstrate core material. We have been using these teaching kits for organ system teaching in the pre-clerkship year. Teaching kits offer several advantages. They make it easier to recruit seminar leaders through efficient use of their time. The use of duplicated films and a syllabus ensures that all students cover the same material. The syllabus can be used to generate examination questions for reinforcement of important concepts. The kits are also available to students to review alone and can be readily updated as required.

Brief communication: a simple model for teaching double-contrast examinations of the gastrointestinal tract.

Good double-contrast studies of the stomach and colon demand a meticulous examination technique. The radiology resident learning this technique often has difficulty understanding the effect of patient positioning on the barium and air. A simple three-dimensional model is described here which helps the resident understand the rationale for the sequence of manoeuvres required to move the barium and air through the gut.

Digital teleradiology: Seaforth--London network.

A total digital teleradiology system using a prototype DuPont laser beam scanner (DTR 2000) and a Bell Canada digital transmission network was evaluated. A total of 489 radiographic and ultrasonographic examinations were transmitted for interpretation from a 41-bed rural community hospital in Seaforth to the University Hospital in London, Ontario, 80 km away. There was concurrence in 98% of these examinations, i.e. the laser-sensitive facsimile film clearly duplicated the original film findings and allowed a confident interpretation to be made. We conclude that this system could readily serve the needs of family physicians in rural communities for radiologic consultation, diagnosis, management, and triage of patients 24 hours per day.

Accuracy of nonorthogonal magnetic resonance imaging in acute disruption of the anterior cruciate ligament.

A controlled, prospective study of 30 patients with suspected acute internal derangement of the knee was undertaken to evaluate the sensitivity, specificity, predictive value, and accuracy of nonorthogonal (oblique) sagittal magnetic resonance imaging (MRI) in the assessment of anterior cruciate ligament (ACL) injuries. Thirty patients with acute hemarthroses underwent MRI within 12 days of injury, followed by arthroscopy within 24 h of the MRI. A control population of 30 chondromalacia patients underwent similar evaluation. In the acute hemarthrosis patient population, the incidence at arthroscopy of acute complete ACL tears was 60% (18/30); of partial ACL tears, 13.3% (4/30); and of chronic tears, 10% (3/30). A normal ACL was found in 16.6% (5/30) of patients. In the MRI evaluation of patients with suspected ACL injury the following results were obtained for both acute and chronic complete disruption on orthogonal (sagittal) and nonorthogonal (oblique sagittal) imaging, respectively: sensitivity, 61 (16/26) versus 100%; specificity, 70 (21/34) versus 100%; positive predictive value, 61 (16/26) versus 100%; negative predictive value 70 (24/34) versus 100%; and accuracy, 66 (40/60) versus 100%. In the evaluation of partial ACL injury, four partial tears were correctly diagnosed on nonorthogonal MRI, with one false-positive diagnosis. Orthogonal imaging failed to correctly identify any of the partial ACL injuries. Two patients in the control population demonstrated evidence of chronic ACL tears. We believe that we have demonstrated the superiority of T2-weighted nonorthogonal sagittal over conventional orthogonal sagittal ACL MRI in the evaluation of ACL injury.