Impact of primary tumour location on colorectal liver metastases: A systematic review

BACKGROUND Colorectal cancer(CRC)is the third most common cause of cancer-related death worldwide.Despite significant advances in screening,surgical management and adjuvant therapies,average 5-year survival seldom exceeds 60%in most developed nations.Metastatic disease represents the primary cause of mortality in patients with CRC,and the liver is the most common location for distant tumour spread.Up to 25%of patients are found to have synchronous liver metastases at the time of diagnosis and a further 30%-40%will develop metachronous disease in the course of follow-up.It has been suggested that primary tumour location[right side versus left side,primary tumour location(PTL)]can influence oncological outcomes in this patient group and that this should be considered in prognostic models and therapeutic decision-making algorithms.This suggestion is not universally accepted and there have been conflicting reports in the literature to date.AIM To provide a comprehensive summary of the available evidence regarding the impact of PTL on oncological outcomes in patients with colorectal cancer liver metastases(CRCLM).METHODS MEDLINE,EMBASE and COCHRANE were searched for relevant publications using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology.Data on oncological outcomes was then extracted from full text articles that met the predefined inclusion criteria.RESULTS A total of 41 studies were identified that met predefined inclusion criteria for this review.In 21 out of 38 studies that provided data on overall survival,a statistically significant improvement in overall survival was reported in patients with left sided primary tumours.These studies included a total of 13897 patients compared with 4306 patients in the studies that did not show a significant difference.Eight studies noted a similar trend towards improved disease-free or progression-free survival.Several authors observed distinct patterns of relapse after treatment of hepatic metastases according to PTL;for example hepatic recurrence after treatment of CRCLM appears to occur more aggressively with right-sided CRC.CONCLUSION Taken together,the findings of the present review indicate that PTL may have a role as an independent prognostic factor when determining treatment and disease surveillance strategies in CRC.The mechanisms responsible for this variation remain poorly understood,but are likely to relate to molecular,histological and embryological differences,as well as inherent differences in therapeutic sensitivity.

Correlation analysis of liver tumor-associated genes with liver regeneration

AIM: To study at transcriptional level the similarities and differences of the physiological and biochemical activities between liver tumor (LT) and regenerating liver cells. METHODS: LT-associated genes and their expression changes in LT were obtained from databases and scientific articles, and their expression profiles in rat liver regeneration (LR) were detected using Rat Genome 230 2.0 array. Subsequently their expression changes in LT and LR were compared and analyzed. RESULTS: One hundred and twenty one LT-associated genes were found to be LR-associated. Thirty four genes were up-regulated, and 14 genes were down-regulated in both LT and regenerating liver; 20 genes up-regulated in LT were down-regulated in regenerating liver; 21 up-regulated genes and 16 down-regulated genes in LT were up-regulated at some time points and down-regulated at others during LR. CONCLUSION: Results suggested that apoptosis activity suppressed in LT was still active in regenerating liver, and there are lots of similarities and differences between the LT and regenerating liver at the aspects of cell growth, proliferation, differentiation, migration and angiogenesis.

BP180NC16a酶联免疫吸附测定在妊娠期类天疱疮的血清学诊断以及妊娠瘙痒性荨麻疹性丘疹与斑块病鉴别中的作用

Background: Pemphigoid gestationis (PG) is a rare pregnancyassociated subepidermal immunobullous disease that targets hemidesmosomal proteins, particularly BP180. Clinically, PG can resemble the eruption known as polymorphic urticarial papules and plaques of pregnancy (PUPPP), and accurate differentiation between these 2 pruritic pregnancy dermatoses has important implications for fetal and maternal prognoses. Results of epitope mapping studies show that IgG autoantibodies in up to 90%of PG serum samples target the well-defined membrane-proximal NC16a domain of BP180. Objective: To examine the usefulness of a commercially available NC16a domain enzyme-linked immunosorbent assay in the serodiagnosis of PG and in the differentiation of PG from PUPPP. Participants: A total of 412 women consisting of pretreatment patients with PG (n=82), patients with PUPPP (n=164), and age-and sex-matched controls (n=166). Methods: All serum samples were assayed in duplicate. Receiver operating characteristic analyses were performed to determine a cutoff value for the diagnosis of PG and for differentiation from PUPPP and controls. Results: A cutoff value of 10 enzyme-linked immunosorbent assay units was associated with specificity and sensitivity of 96%. Conclusions: The NC16a enzyme-linked immunosorbent assay is highly sensitive and highly specific in differentiating PG from PUPPP, and it is potentially a valuable tool in the serodiagnosis of PG.

与眼内硅油充填相关的中心暗点在硅油取出前形成

Background: Unexplained sudden visual loss after removal of silicone oil from the eye has recently been described. We report the occurrence and features of unexplained central scotoma developing with silicone oil in situ in the vitreous cavity. Methods: A retrospective case series of five patients (from two centres)-who reported a central scotoma commencing during silicone oil tamponade was studied. All patients had vitrectomy for macula-on retinal detachment, with ultra-purified silicone oil tamponade (four out of five had giant retinal tear). Investigations included visual acuity, intraocular pressure, optical coherence tomography, fluorescein angiography, visual fields and electrophysiology. Results: All patients reported a central scotoma that appeared during oil tamponade. Visual acuity fell by a mean of 0.93 LogMAR units after onset of the scotoma. After cataract extraction and oil removal, vision remained reduced by a mean of 0.8 units. The mean duration of oil in the eye was 2.7months when the scotoma was noted by the patient. Investigations were performed after removal of oil. Fluorescein angiography (FFA) was performed in two cases and optical coherence tomography (OCT) in five patients. No abnormality was demonstrated. Electrophysiology was performed in five patients with pattern electroretinography suggestive of macular dysfunction in four patients. Conclusion: This is the first case series describing central scotoma as sociated with silicone oil in situ. Electrophysiology indicated macular dysfunction in most cases. We suggest that early removal of oil in cases with good visual potential should be considered to avoid this sightthreatening complication.

玻璃体内注射曲安奈德治疗非缺血性中央静脉阻塞的黄斑囊样水肿

PURPOSE: The effectiveness of intravitreal triamcinolone acetonide in the treatment of cystoid macular edema from central retinal vein occlusion (CRVO) was investigated. DESIGN: A noncomparative, prospective, interventional case series. METHODS: In a clinical practice, 18 patients were enrolled with nonischemic CRVO and cystoid macular edema. Two milligrams of triamcinolone acetonide were injected into the vitreous of only one eye from each patient. The outcome measures were 1-mm mean central retinal thickness on optical coherence tomography and visual acuity. RESULTS: Mean duration of symptoms before surgery was 2 months (SD, 1.3 months). Ten patients required repeated injections for recurrent cystoidmacular edema (mean,1.8 injections). Mean visual acuity significantly improved from 20/300 to 20/166 (P=.007) at 1 month, 20/100 (P=.0005) at 2 months, 20/130 (P=.007) at 3 months, and 20/150 (P=.02) at 6 months but deteriorated again to 20/270 (not significant) at 12 months. There was a significant improvement in retinal thickness from presentation 518 μm, to 363 μm (P=.03) at 1 month, 304 μm (P=.04) at 2 months, and 353 μm (P=.01) at 3 months but not from presentation at 6 months (mean, 383 μm) and 12 months (mean, 406 μm). Eleven patients suffered intraocular pressure rises requiring intervention. Intravitreal triamcinolone acetonide did not prevent collateral circulation formation, which was seen in 10 patients. CONCLUSION: Intravitreal corticosteroid injection is very effective in reversing cystoid macular edema and improving visual acuity in recent-onset nonischemic CRVO in the first 6 months, but this is unfortunately not sustained at 1 year.

与斑贴试验反应强度有关的副-苯二胺过敏患者的分析

Background: Despite having a positive patch test reaction to para-phenylenediamine (PPD), some patients continue to dye their hair, while others are forced to give up or abandon this practice. This difference in patient behaviour could be due to the degree of sensitization. Objectives: To establish whether the ability to continue dyeing hair in PPD allergic patients is related to the strength of patch test reaction. To note differences in other clinical features in relation to the strength of patch test reaction. Methods We analysed retrospectively the patch test records of 400 sequential PPD-positive patients for the strength of patch test reaction (+, ++, +++) and different clinical features. Data were analysed using Cochran-Mantel-Haenszel χ2 tests. Results: There was a strong linear relationship between the strength of patch test reaction and continuation with hair dyeing. Patients were more likely to report a history of hair dye reaction with increasing strength of patch test reaction. There was no difference in strength of patch test reaction in relation to age, site of rash, occupation (hairdressing) or history of atopic eczema. Overall concomitant reactivity with related aromatic amine allergens (benzocaine,N-isopropyl-Nphenyl-para-phenylenediamine, para-aminobenzoic acid) was infrequent. Conclusions: Patients with stronger patch test reactions (++, +++) are more likely to have a clear history of reacting to hair dye and are less likely to still be dyeing their hair.

由依诺肝素继发的湿疹样斑疹

Low-molecular-weight heparins are used extensively in acute medicine. They are generally well tolerated but may cause a rare, eczema-like type IV hypersensitivity reaction. We report 3 cases of this eruption and speculate that it may be significantly under-reported due to misidentifying the causal drug, which may have serious consequences. We discuss treatment alternatives such as fondaparinux sodium, which may rarely cross-react.

染色体1完全性父系等二倍体导致Herlitz交界型大疱性表皮松解症

Herlitz junctional epidermolysis bullosa (JEB) is an autosomal recessive mecha nobullous disorder that results from loss-of-function mutations in the genes e ncoding the basement membrane component, laminin 5. Typically, there are framesh ift, splice site or nonsense mutations on both alleles of either theLAMA3,LAMB3o rLAMC2genes,withaffectedindividuals inheriting one mutated allele from each pare nt. In this report, we describe a patient with Herlitz JEB in whom DNA analysis revealed homozygosity for the recurrent nonsense mutation R635X in LAMB3, locate d on chromosome 1q32.2. However, screening of parental DNA showed that although the patient’s father was a heterozygous carrier of this mutation, the mother’s DNA showed only wild-type sequence. Subsequent genotype analysis using 13 micr osatellite markers spanning chromosome 1 revealed that the affected child was ho mozygous for the entire seriesofmarkerstestedandthatalloftheallelesoriginatedfro m the father. These results indicate that the Herlitz JEB phenotype in this pati ent is due to complete paternal isodisomy of chromosome 1 and reduction to homoz ygosity of the mutant LAMB3 gene locus. This is the fourth case of uniparental d isomy to be described in Herlitz JEB, but it represents the first example of com plete paternal isodisomy for chromosome 1 with a pathogenic mutation in the LAMB 3 gene. These findings have important implications for mutation screening in JEB and for genetic counselling.

妊娠期肝内胆汁淤积症与妊娠期瘙痒患者的谷胱甘肽S转移酶和肝功能

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancyspecific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (±2) weeks compared with controls (400%difference; 95%CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433%difference; 95%CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.

Clinico-pathological aspects of colorectal serrated adenomas

AIM： To study the association of colorectal serrated adenomas （SAs） with invasive carcinoma, local recurrence, synchronicity and metachronicity of lesions. METHODS： A total of 4536 polyps from 1096 patients over an eight-year period （1987-1995） were retrospectively examined. Adenomas showing at least 50% of serrated architecture were called SAs by three reviewing pathologists. RESULTS： Ninety-one （2%） of all polyps were called SAs, which were found in 46 patients. Invasive carcinomas were seen in 3 out of 46 （6.4%） patients, of whom one was a case of familial adenomatous polyposis （FAP）. A male preponderance was noted and features of a mild degree of dysplasia were seen in majority （n=75, 83%） of serrated adenomas. Follow-up ranged 1-12 years with a mean time of 5.75 years. Recurrences of SAs were seen in 3 （6.4%） cases, synchronous SAs in 16 （34.8%） cases and metachronous SAs in 9 （19.6%） cases. CONCLUSION： Invasive carcinoma arising in serrated adenoma is rare, accounting for 2 （4.3%） cases studied in this series.

伴有下方破裂的原发性孔源性视网膜脱离的治疗

Background: Rhegmatogenous retinal detachments (RRD) with inferior breaks are usually treated by scleral buckling (SB) or pars plan a vitrectomy (PPV) or a combination of both methods. However, applying a SB duri ng PPV may produce a risk of choroidal haemorrhage. Following a recent pilot stu dy showing that such cases can be safely treated by PPV without SB the authors r e examined their management of RRD in which inferior breaks were present. Metho ds: All patients had a detached vitreous and a complex configuration of retinal breaks. A case control study was performed to analyse the surgical methods and results of PPV on 48 consecutive patients with RRD associated with inferior brea ks and 48 age/sex matched controls who underwent PPV for RRD without inferior br eaks. Exclusion criteria were giant retinal tears, retinal dialysis, trauma, pro liferative vitreoretinopathy (PVR) grade B or higher, schisis detachments, and e yes that had been operated previously for RRD. A simple algorithm was followed t o manage patients with inferior breaks. All patients underwent a standard three port PPV with intraocular gas tamponade without supplementary SB. Patients were asked to posture face up or right or left side down for 1 week. Results: 39 of t he 48 patients (81.3%) with inferior breaks were treated successfully with one operation. 41 of 48 patients (85.4%) control patients achieved primary success. The final success rate was 95.8%in both groups. There was no statistical diffe rence between the two groups. When all the cases of RRD were analysed (including external plomb/non drain procedures) the primary success rate was 89%and fina l success rate 97.5%Conclusions: This study has shown that acceptable success r ates can be achieved using PPV alone to treat RRD with inferior breaks. Complica tions are minimised and patients in this high risk group have an 81%chance of p rimary success. Pars plana vitrectomy and gas will successfully reattach the ret ina and a supplementary SB, to support the inferior retina, is unnecessary as th e intraocular gas, and face up or, right or left side down positioning will tamp onade breaks satisfactorily.

头痛和偏头痛的初级护理:大样本人群的会诊、用药和转诊率

Background/Aims: Headache is the most common new neurological symptom seen by general practitioners and neurologists. This study describes headache consultation, prescription, and referral rates in a large sample of UK general practices. Methods: Analysis of data from patients ≥15 years registered at 253 UK general practices diagnosed with headache/migraine from 1992 to 2000. Rates were age standardised using the European standard population for reference. Results: There were 13.2 million patient years of observation. Headache consultation rates were 6.4/100 patients/year in women and 2.5 in men. They were highest at 15-24 years (15.8/100 in women; 5.8/100 in men), decreasing with age. Antimigraine drugs were prescribed at 36.7%of consultations for women and 26.6%for men. Among refer rals to specialists, 55%were to neurology and 30%to general medicine. The neurology referral rate in patients with headache was 2.1/100, and was higher in men (2.7/100) than women (1.9/100). Conclusions: These results provide precis e age specific and age standardised estimates for headache consulting in general practice, in addition to prescribing and referral to specialist care. Consultat ion rates are highest in young women; hospital referrals peak in middle aged men . Research is needed into reasons for referral, and on better ways of delivering headache services.

CD56+免疫表型的蕈样肉芽肿

We report 3 cases of mycosis fungoides (MF) with a CD56+cytotoxic immunophenotype. Each patient presented with a different clinical phenotype:one exhibited limited poikilodermatous patches (skin stage T1); one, widespread hypopigmented lesions (skin stage T2); and one, poikiloderma with a single cutaneous tumor (skin stage T3). MF was confirmed both histologically and by the presence of a T cell receptor clone in lesional skin in all cases. CD56 and T cell intracellular antigen-1 were expressed by the malignant lymphocytes in all patients and two expressed CD8. No sample demonstrated loss of the pan T-cell markers CD2 or CD3. None of the 3 developed systemic disease and T-cell receptor gene analysis of peripheral blood was polyclonal in all cases. Only 3 cases of CD56+MF have been reported previously, none of which exhibited tumor-stage disease. Currently, the disease in our patients appears to be behaving in a manner similar to that predicted for MF with a normal immunophenotype but the prognosis has to be guarded in view of the rarity of this subtype.

皮肤对CS喷雾的非特异性反应

CS spray (2-chlorobenzylidenemalononitrile 5%w/v inmethyl isobutyl ketone) has been used by the police force in the UK as an incapacitant for nearly a decade. It causes a number of wellrecognized cutaneous reactions, which are generally regarded as short-lived. These include skin burning, erythema and blistering. However, a range of unpredictable cutaneous reactions to CS spray may also occur. We have found contact allergy, leukoderma, initiation or exacerbation of seborrhoeic dermatitis, and aggravation of rosacea following CS spray exposure in 6 police officers and 1 doorman. These skin reactions have required long-term changes in working practice for the affected individuals. Police officers may have repeated exposure to CS spray during their training and in their work, and designated police officers carry CS spray canisters daily in the line of duty. They may therefore be at greater risk of exposure to CS spray and its unintended effects than many assailants.Chemical exposure and symptoms of hand dermatitis in construction

社区相关的耐甲氧西林金黄色葡萄球菌:对儿科医师的警示

Community associated methicillin resistant Staphylococcus aureus(CA-MRSA) is an emerging pathogen typically associated with skin and soft tissue infection, with occasional reports of fatality in previously healthy children and young adults. We report a case of invasive CA-MRSA and highlight the potential impact of such infections on empirical treatment of staphylococcal infections.

p63基因错义突变R298Q导致的ADULT外胚叶发育异常综合征

Several ectodermal dysplasia syndromes have been shown to result from mutations in the gene that encodes the transcription factor p63. We describe an 11- year-old boy, with clinically normal parents, who had a developmental disorder that resembled EEC (ectrodactyly ectodermal dysplasia-clefting) syndrome (OMIM 604292). He had ectrodactyly and missing middle fingers bilaterally, onychodysplasia, hypodontia with missing teeth, hypohidrosis and lacrimal duct obstruction. DNA sequencing disclosed a heterozygous G ?ú .A substitution at nucleotide 893, that converts an arginine residue (CGA) to glutamine (CAA), the mutation being designated R298Q. This mutation occurs within the DNA-binding domain of p63, and is close to many of the published EEC syndrome mutations. However, R298Q has been described once previously in a large German pedigree, not with EEC syndrome, but another ectodermal dysplasia disorder, ADULT (acro-dermato-unguallacrimal-tooth) syndrome (OMIM 103285). Further clinical assessment in our patient revealed that, apart from not having cleft lip and/or palate, he had an exfoliative dermatitis of his hands and feet, and some freckling on his face and shoulders. Collectively, these features support a diagnosis of ADULT syndrome. This study has identified a specific genotype- phenotype correlation in a rare ectodermal dysplasia syndrome and the findings are useful in improving genetic counselling in this family.

黄斑裂孔的手术效果:手术处理和临床治疗的意义

Purpose: The optimal method and timing of the surgical treatment for idiopathic macular holes remains unknown. The aim of this retrospective study was to identify factors associated with anatomical and visual success in macular hole surgery. Methods: Case records of 55 patients undergoing macular hole surgery at three units in the 2- year period up to July 2002 were reviewed to identify factors associated with anatomical and visual success. The following potential prognosticators were evaluated: patient age, hole stage, hole latency prior to surgery, preoperative acuity, simultaneous phacoemulsification, and intraocular lens implantation, internal limiting membrane peeling with and/or without indocyanine green, and postoperative posturing. Results: The duration of preoperative symptoms, indocyanine green-assisted internal limiting membrane peeling, hole stage, and better preoperative visual acuity were associated with both anatomical success and regaining a postoperative visual acuity of 6/12 or better. Discussion: The closure rate in patients undergoing surgery within 1 year of onset was 94.0% , and in those waiting 1 year or more it was 47.4% . Clinical governance and quality issues should dictate that NHS macular hole surgery is available to all within 1 year of onset. This study showed no adverse effect of ICG dye retinal staining. The results support the use of a “ patient-friendly” approach of simultaneous cataract surgery with no prone postoperative posturing.

正在接受丙型肝炎治疗的一文身男性出现系统性结节病

A heavily tattooed man presented with nodular, ulcerated sarcoidal lesions distributed throughout all the colours of his tattoos. The lesions developed within the confines of his tattoos 4 months into therapy with ribavirin and interferon-α for chronic hepatitis C. This appears to be the first case of sarcoidosis in association with numerous pigment colours as well as dual therapy for hepatitis C.

先天性血管萎缩性皮肤异色症并发汗孔角化症及双侧虹膜发育不全的特殊病例1例

Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive genodermatosis characterized by poikiloderma and the variable presence of other features including skeletal and ocular abnormalities, ectodermal defects, and suscept-ibility to certain malignancies. We report a 40-year-old woman with known RTS who developed porokeratoses on her limbs in adulthood, an association that has not previou-sly been reported. In addition, she had bilateral iris dysgenesis, which has only been described once before in RTS.

硬化性苔癣细胞外基质蛋白-1自身抗体IgG的特征

Although the precise aetiology of lichen sclerosus is unknown, evidence for an autoimmune basis to the disorder is emerging. Indeed, circulating IgG autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been demonstrated in the sera of about 75%of affected individuals. To assess this humoral immune response further, immunoblotting was performed using bacterial recombinant proteins spanning different domains of the ECM1 protein. The aim was to identify autoantibody-reactive sites recognized by 90 lichen sclerosus sera. The subclass distribution of anti-ECM1 IgG autoantibodieswas also determined in 54 lichen sclerosus sera. Immunoblotting showed that the IgG autoantibodies from lichen sclerosus patients recognize multiple antigenic reactive sites on the ECM1 protein within both the amino terminus (50/90, 55.6%) and the protein loop cysteine-rich repeat domains (54/90, 60%), although few sera (7/90, 7.8%) had antibodies to the carboxyl terminus of ECM1. IgG subclass analysis revealed that the anti-ECM1 autoantibodies belong predominantly to the IgG2 subclass (48/54, 88.9%), either IgG2 alone (28/54, 51.9%) or in combination with one or more other IgG subclasses. No correlation was found between the site(s) of the ECM1 epitopes or the anti-ECM1 IgG profile and any specific clinical parameters. Nevertheless, characterization of anti-ECM1 antibodies does provide further insight into humoral immune responses and understanding disease mechanisms in lichen sclerosus.