Abstract The presentation, pathology and treatment of 30 patients with acute bleeding from gastric malignancies has been reviewed. Patients usually have a history of symptoms of less than 6 months prior to bleeding. Adenocarcinoma was the commonest type of tumour, and 74per cent were stage IV lesions. The proportion of lesions in the body of the stomach (57per cent) was greater than expected, suggesting that these are different populations of gastric tumour. Laparotomy was undertaken in 20 patients, 12 of whom had a resection. Resection was associated with a median survival of 17·0 months. Those with unresectable tumours or who were treated only by supportive measures had a median survival of only 2·5 months (P < 0·01). Evidence of peritoneal or liver involvement should contraindicate surgical intervention as these patients have a high postoperative mortality rate.
Abstract Background The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients. Objectives To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. Methods OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. Results Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar. Conclusions Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials. What is already known about this topic? Cutaneous squamous cell carcinoma (cSCC) is significantly more common in immunocompromised individuals including organ transplant recipients (OTRs) compared with immunocompetent populations. cSCC chemoprevention activity of sunscreen and 5-fluorouracil-based (5-FU) actinic keratosis (AK) treatments has been demonstrated in randomized controlled trials (RCTs) in immunocompetent populations but not in OTRs. AKs are cSCC precursors and their clearance and prevention are generally regarded as surrogate endpoint biomarkers for potential cSCC chemoprevention activity. What does this study add? SPOT (SCC Prevention in OTRs using Topical treatments) has confirmed that RCTs of OTR-cSCC chemoprevention with topical AK treatments are feasible. It also suggests that topical 5-FU may be superior to 5% imiquimod and sunscreen in AK clearance and prevention. Together with recent evidence from several RCTs in the general population, these data provide a compelling rationale for further studies of intervention with 5-FU-based topical chemoprevention approaches in OTR-cSCC prevention.
Low-grade gliomas represent the most frequent primary brain tumors in children, and are also an important category of brain neoplasms in young adults. They are characterized by slow growth, but often associated with increased morbidity, as well as mortality in the subset that develop histologic progression. Pathologically they correspond to WHO grade I or II and include pilocytic astrocytoma (PA), pilomyxoid astrocytoma variant, angiocentric glioma, diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, and pleomorphic xanthoastrocytoma (PXA). Although all low-grade glioma subtypes may develop in children and adults, and be histologically indistinguishable in these two populations, there are important clinical and molecular differences. As a rule, low-grade gliomas in adults have a greater tendency for histologic progression and more aggressive clinical behavior than those in children. With respect to genetic alterations, activating BRAF alterations and increased MAPK pathway signaling are near universal features of the circumscribed low-grade glioma group (e.g., PA and PXA). Whole exome/genome sequencing efforts and high resolution copy number platforms have also provided important biologic insights in these tumors, with adult low-grade diffuse gliomas containing frequent ATRX, TP53 mutations (astrocytomas), as well as 1p19q co-deletions, CIC, FUBP1 and TERT promoter mutations (oligodendrogliomas). Conversely, alterations in FGFR1, MYB, and MYBL1 are frequent events in pediatric low-grade diffuse gliomas. In this review we summarize our current knowledge of the diagnostic and molecular pathology of these tumors, and explore possible avenues for targeted therapeutics.
Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited.
Summary Del (9q) is a recurrent cytogenetic abnormality in acute myeloid leukaemia (AML). We report an analysis of 81 patients with del(9q) as a diagnostic karyotypic abnormality entered into the Medical Research Council AML trials 10, 11 and 12. Patients were divided into three groups: (i) Sole del (9q), 21 patients; (ii) Del(9q) in association with t(8;21), 29 patients; (iii) Del(9q) in association with other cytogenetic abnormalities, 31 patients. Sole del(9q) was associated with a characteristic bone marrow phenotype at diagnosis: a single Auer rod was found in all cases examined. There was also an association with erythroid dysplasia (74%) and granylocytic lineage vacuolation (90%). The incidence of all three of these features was significantly higher ( P < 0·05) in the sole del(9q) group compared with control cases lacking del(9q). The overall survival (OS) of all 81 patients was compared with a control group of 1738 patients with normal cytogenetics entered in the same trials over the period of investigation. The 5‐year OS for patients with del(9q) was 45%, compared with 35% for the control group ( P = 0·09). Patients with del(9q) in association with t(8;21) had a 5‐year OS of 75%, which was significantly better than the groups with either sole del(9q) (40%) and del(9q) with other abnormalities (26%; P = 0·008). Karyotyping indicated a common area of deletion in the region 9q21–22, which was present in 94% of cases. It is likely that the deletion of single or multiple tumour suppressor genes located in this region may underlie the pathogenesis of del (9q) AML.
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