Interventional radiology in the management of malignant biliary obstruction

Malignant biliary obstruction is commonly due to pancreatic carcinoma,cholangiocarcinoma and metastatic disease which are often inoperable at presentation and carry a poor prognosis.Percutaneous biliary drainage and stenting provides a safe and effective method of palliation in such patients,thereby improving their quality of life.It may also be an adjunct to surgical management by improving hepatic and,indirectly,renal function before resection of the tumor.

The impact of new technology on surgery for colorectal cancer

Advances in technology continue at a rapid pace and affect all aspects of life, including surgery. We have reviewed some of these advances and the impact they are having on the investigation and management of colorectal cancer. Modern endoscopes, with magnifying, variable stiffness and localisation capabilities are making the primary investigation of colonic cancer easier and more acceptable for patients.Imaging investigations looking at primary, metastatic and recurrent disease are shifting to digital data sets, which can be stored, reviewed remotely, potentially fused with other modalities and reconstructed as 3 dimensional (3D) images for the purposes of advanced diagnostic interpretation and computer assisted surgery. They include virtual colonoscopy, trans-rectal ultrasound, magnetic resonance imaging, positron emission tomography and radioimmunoscintigraphy. Once a colorectal carcinoma is diagnosed, the treatment options available are expanding. Colonic stents are being used to relieve large bowel obstruction, either as a palliative measure or to improve the patient's overall condition before definitive surgery. Transanal endoscopic microsurgery and minimally invasive techniques are being used with similar outcomes and a lower mortality, morbidity and hospital stay than open trans-abdominal surgery. Transanal endoscopic microsurgery allows precise excision of both benign and early malignant lesions in the mid and upper rectum. Survival of patients with inoperable hepatic metastases following radiofrequency ablation is encouraging. Robotics and telemedicine are taking surgery well into the 21(st) century. Artificial neural networks are being developed to enable us to predict the outcome for individual patients. New technology has a major impact on the way we practice surgery for colorectal cancer.

Overview of coronary artery variants, aberrations and anomalies

Coronary artery anomalies and variants are relatively uncommon congenital disorders of the coronary artery anatomy and constitute the second most common cause of sudden cardiac death in young competitive athletes. The rapid advancement of imaging techniques, including computed tomography, magnetic resonance imaging, intravascular ultrasound and optical coherence tomography, have provided us with a wealth of new information on the subject. Anomalous origin of a coronary artery from the contralateral sinus is the anomaly most frequently associated with sudden cardiac death, in particular if the anomalous coronary artery has a course between the aorta and the pulmonary artery. However, other coronary anomalies, like anomalous origin of the left coronary artery from the pulmonary artery, atresia of the left main stem and coronary fistulae, have also been implicated in cases of sudden cardiac death. Patients are usually asymptomatic, and in most of the cases, coronary anomalies are discovered incidentally during coronary angiography or on autopsy following sudden cardiac death. However, in some cases, symptoms like angina, syncope, heart failure and myocardial infarction may occur. The aims of this article are to present a brief overview of the diverse coronary variants and anomalies, focusing especially on anatomical features, clinical manifestations, risk of sudden cardiac death and pathophysiologic mechanism of symptoms, as well as to provide valuable information regarding diagnostic workup, follow-up, therapeutic choices and timing of surgical treatment.

Clinical utility of anti-p53 auto-antibody: Systematic review and focus on colorectal cancer

Mutation of the p53 gene is a key event in the carcinogenesis of many different types of tumours. These can occur throughout the length of the p53 gene. Anti-p53 auto-antibodies are commonly produced in response to these p53 mutations. This review firstly describes the various mechanisms of p53 dysfunction and their association with subsequent carcinogenesis. Following this, the mechanisms of induction of anti-p53 auto-antibody production are shown, with various hypotheses for the discrepancies between the presence of p53 mutation and the presence/absence of anti-p53 auto-antibodies. A systematic review was performed with a descriptive summary of key findings of each anti-p53 auto-antibody study in all cancers published in the last 30 years. Using this, the cumulative frequency of anti-p53 autoantibody in each cancer type is calculated and then compared with the incidence of p53 mutation in each cancer to provide the largest sample calculation and correlation between mutation and anti-p53 auto-antibody published to date. Finally, the review focuses onthe data of anti-p53 auto-antibody in colorectal cancer studies, and discusses future strategies including the potentially promising role using anti-p53 auto-antibody presence in screening and surveillance.

Chemotherapy plus percutaneous radiofrequency ablation in patients with inoperable colorectal liver metastases

AIM:To access the efficacy of chemotherapy plus radiofrequency ablation(RFA)as one line of treatment in inoperable colorectal liver metastases.METHODS:Eligible patients were included in three PhaseⅡstudies.In the first study percutaneous RFA was used first followed by 6 cycles of 5-fluorouracil,leucovorin and irinotecan combination(FOLFIRI)(adjunctive chemotherapy trial).In the other two,chemotherapy(FOLFIRI or 5-fluorouracil,leucovorin and oxaliplatin combination)up to 12 cycles was used first with percutaneous RFA offered to responding patients (primary chemotherapy trials).RESULTS:Thirteen patients were included in the adjunctive chemotherapy trial and 17 in the other two.At inclusion they had 1-4 liver metastases(up to 6.5 cm in size).Two patients died during chemotherapy.All patients in the adjunctive chemotherapy trial and 44%in the primary chemotherapy studies had their metastases ablated.Median PFS and overall survival in the adjunctive study were 13 and 24 mo respectively while in the primary chemotherapy studies they were 10 and 21 mo respectively.Eighty one percent of the patients had tumour relapse in at least one previously ablated lesion.CONCLUSION:Chemotherapy plus RFA in patients with low volume inoperable colorectal liver metastases seems safe and relatively effective.The high local recurrence rate is of concern.

Novel therapies for constipation

Constipation is a common medical problem and when standard laxatives fail it can be difficult to treat.Different aetiologies require tailored therapeutic approaches.Simple constipation may only require dietary manipulation while severe neurological or slow transit constipation may need pharmacologic intervention.Recently new drug therapies have been introduced.PubMed and Ovid were searched for reviews,systematic reviews and meta-analysis published since 2003 using the terms:constipation,Prucalopride,Linaclotide and Lubiprostone.This review summarizes potential novel therapies identified as effective in the management of chronic constipation.Prucalopride is a selective 5-hydroxytryptamine receptor agonist.The prucalopride study was in patients,largely women with idiopathic constipation showed improved spontaneous complete bowel movement(SCBM)at a dose of 2 mg a day with few adverse events reported.Linaclotide is a 14-amino acid peptide guanylate cyclase-C agonist.The linaclotide study was carried out in patients with irritable bowel syndrome,constipation group(IBS-C).There was significant improvement of bowel evacuation and symptom resolution in patients on the active treatment arm.Lubiprostone activates type-2 chloride channels,increasing intestinal fluid secretion.In the trials of this drug,the lubiprostone arms had a greater mean number of SCBM.The novel therapies,prucalopride,lubiprostone,and linaclotide had very different modes of action yet,all three have been shown to be efficacious and safe in the treatment dose for constipation.

Prevention of post-ERCP pancreatitis

Post-procedure pancreatitis is the most common complication of endoscopic retrograde cholangio pan-creatography(ERCP) and carries a high morbidity and mortality occurring in at least 3%-5% of all procedures. We reviewed the available literature searching for "ERCP" and "pancreatitis" and "post-ERCP pancreatitis". in PubMed and Medline. This review looks at the diag-nosis, risk factors, causes and methods of preventing post-procedure pancreatitis. These include the evidence for patient selection, endoscopic techniques and phar-macological prophylaxis of ERCP induced pancreatitis. Selecting the right patient for the procedure by a risk benefits assessment is the best way of avoiding unnec-essary ERCPs. Risk is particularly high in young women with sphincter of Oddi dysfunction(SOD). Many of the trials reviewed have rather few numbers of subjects and hence difficult to appraise. Meta-analyses have helped screen for promising modalities of prophylaxis. At present, evidence is emerging that pancreatic stent-ing of patients with SOD and rectally administered non-steroidal anti-inflammatory drugs in a large unselected trial reduce the risk of post-procedure pancreatitis. A recent meta-analysis have demonstrated that rectally administered indomethecin, just before or after ERCP isassociated with significantly lower rate of pancreatitis compared with placebo [OR = 0.49(0.34-0.71); P = 0.0002]. Number needed to treat was 20. It is likely that one of these prophylactic measures will begin to be increasingly practised in high risk groups.

Development and course of heart failure after a myocardial infarction in younger and older people

Background Acute myocardial infarction （AMI） is a common cause of heart failure （HF）, which can develop soon after AMI and may persist or resolve or develop late. HF after an MI is a major source of mortality. The cumulative incidence, prevalence and resolution of HF after MI in different age groups are poorly described. This study describes the natural history of HF after AMI according to age. Methods Patients with AMI during 1998 were identified from hospital records. HF was defined as treatment of symptoms and signs of HF with loop diuretics and was considered to have resolved if loop diuretic therapy could be stopped without recurrence of symptoms. Patients were cate- gorised into those aged 〈 65 years, 65-75 years, and 〉 75 years. Results Of 896 patients, 311,297 and 288 were aged 〈 65, 65-75 and 〉75 years and of whom 24%, 57% and 82% had died respectively by December 2005. Of these deaths, 24 （8%）, 68 （23%） and 107 （37%） oc- curred during the index admission, many associated with acute HF. A further 37 （12%）, 63 （21%） and 82 （29%） developed HF that persisted until discharge, of whom 15, 44 and 62 subsequently died. After discharge, 53 （24%）, 55 （40%） and 37 （47%） patients developed I-IF for the first time, of whom 26%, 62% and 76% subsequently died. Death was preceded by the development of HF in 35 （70%）, 93 （91%） and 107 （85%） in aged 〈 65 years, 65-75 years and 〉75 years, respectively. Conclusions The risk of developing HF and of dying after an MI in- creases progressively with age. Regardless of age, most deaths after a MI are preceded by the development of HF.

Differential effects of atrial and brain natriuretic peptides on human pulmonary artery:An in vitro study

BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection,as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared.Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61gf was applied.After equilibration for 60 min,rings were pre-constricted with 11.21μmol/L PGF2α(EC80),and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96±0.21 and 7.54±0.18,respectively,and the maximum efficacy(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax of ANP reduced from-0.96gf to-0.675gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries,and inhibits relaxation to ANP.Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure.This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.

N末端B型利钠肽前体对心房颤动患者严重结构性心脏病的诊断性效用

目的:用受试者操作特征(ROC)分析评估N末端B型利钠肽前体(NT-proBNP)在诊断房颤(AF)患者严重结构性心脏病(MSHD)中的作用,并与窦性心律(SR)患者进行比较。

慢性心力衰竭患者以磁共振血管造影检出肾动脉狭窄的流行病学特征、相关因素及预后

作者的目的是观察慢性心力衰竭(HF)患者中显著肾动脉狭窄(RAS)相关的患病率、发病率以及死亡率,同时探讨3年随访期内血管紧张素转换酶(ACE)抑制剂和利尿剂在该人群中的使用情况。确定了97例显著肾功能不全(RD;定义为计算所得肾小球滤过率<60ml/min)患者和38例无RD的患者,

经腹腔镜右半结肠切除术与开腹右半结肠切除术:一项病例对照研究

PURPOSE: The purpose of our study was to examine all laparoscopic right hemicolectomies performed for cancer in our unit and to compare them with a case control series of open right hemicolectomies, with emphasis on long term survival. METHODS: In a retrospective case control series of right hemicolectomies, those done laparoscopically were compared with an age matched and stage matched series of patients who underwent open surgery. Survival was analyzed with the Kaplan Meier method. RESULTS: Ninety nine patients were included in the study, 33 laparoscopic and 66 open. Mean age 69.7 years. Dukes staging was the same between the two groups and mean follow up period was 65.7 months. There were six laparoscopic conversions. The number of days patients were kept nil by mouth was significantly less in the laparoscopic cohort, with a mean of 2.4 days vs. a mean of 3.65 days (P = 0.005, Mann Whitney U test). The number of days during which patients required parenteral opiates was significantly less in the laparoscopic cohort, with a mean number of days of 2.5, in contrast to 4.5 days in the open group (P = 0.008, Mann Whitney U test). When overall survival was compared between the open and laparoscopic groups, no difference was found, with a mean overall survival of 40 months in the laparoscopic cohort and 39.4 months in the open cohort (P = 0.348, log rank test). CONCLUSION: Laparoscopic right hemicolectomy for cancer does not compromise long term survival and affords the advantage of a shorter period of postoperative ileus and decreased analgesia requirements.

Severe monobacterial necrotizing soft tissue infection by group A Streptococcus:A surgical emergency

Eight percent of necrotizing soft tissue infections(NSTI) are attributable to group A Streptococci(GAS),and among these,50%develop streptococcal toxic shock syndrome.The reported mortality associated with NSTI reaches 32%.We present cases of two healthy individuals with minor GAS skin infection which developed to a rapidly progressed NSTI and sepsis despite of the antibiotic treatment,aiming to discuss the lessons learned from the course and management of these patients.

Characterization of optimal resting tension in human pulmonary arteries

AIM To determine the optimum resting tension(ORT) for in vitro human pulmonary artery(PA) ring preparations.METHODS Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution(Krebs).The pulmonary arteries were then cut into 2 mm long rings.PA rings were mounted in 25 m L organ baths or 8 m L myograph chambers containing Krebs compound(37 ℃,bubbled with 21% O_2:5% CO_2) to measure changes in isometric tension.The resting tension was set at 1-gram force(gf) with vessels being left static to equilibrate for duration of one hour.Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf.Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension(1.2,1.4,1.6,1.8 and 2.0 gf).RESULTS Twenty PA rings of internal diameter between 2-4 mmwere prepared from 4 patients.In human PA rings incrementing the tension during rest stance by 0.6 gf,up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension.Further enhancement of active tension by 0.4 gf,up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction.Both Myograph and the organ bath demonstrated identical conclusions,supporting that the radial optimal resting tension for human PA ring was 1.61 g.CONCLUSION The radial optimal resting tension in our experiment is 1.61 gf(15.78 m N) for human PA rings.

Pancreatic cancer:A model cancer for the study of the therapeutic effects of anticoagulants

Cancer-related thromboembolic disease is a well recognized syndrome since first described by Armand Trousseau in 1865.Preventing the morbidity and mortality related to thromboembolism in these patients is becoming a priority research area with the advent of new anti-coagulants.It is only recently that randomized trials of improved quality are been undertaken to study this question.Many of these trials however are still not accounting for the heterogeneity of "cancer" in terms of anatomical site,histology,stage and treatment.This editorial review highlights why pancreatic cancer may serve as a model malignancy to study this question.

Can palliative radiotherapy influence prostate-specific antigen response in patients with castrate-resistant prostate cancer treated with systemic therapy(chemotherapy or abiraterone)?——a report of three cases

Palliative radiotherapy(pRT) is primarily employed for palliation of bone pain in patients with castrate-resistant prostate cancer(CRPC). However, evidence that p RT influences prostate-specific antigen response in patients with CRPC on systemic therapy is lacking. We describe three cases of CRPC progressing after treatment with docetaxel(n=2) and abiraterone(n=1), who responded unusually after p RT for bone pain with the development of a significant biochemical response and restoration of response to systemic therapy. The possibility of p RT influencing metastatic disease in CRPC has not been previously reported, and raises the possibility of radiation-induced modulation of anti-tumor immune response mechanisms that may play a role in the restoration of response to systemic treatment.

Review of vedolizumab for the treatment of ulcerative colitis

The review summarises the key data on the efficacy and the safety of vedolizumab in the management of ulcerative colitis.

Sequential maximum androgen blockade(MAB) in minimally symptomatic prostate cancer progressing after initial MAB: two case reports

＂Ihe management of castrate-resistant prostate cancer progressing after maximum androgen blockade （MAB） has evolved in the last decade with the development of several novel therapeutic options. However, the initial therapeutic strategy in these patients usually involves withdrawal of anti-androgen that can be associated with biochemical response in approximately 20% of patients. Notably; we have observed evidence of sustained biochemical response in two patients following second- and third-line MAB using rechallenge schedule of previously administered anti-androgen after latent interval. The possibility of response following sequential MAB using the same anti-androgen agent has not yet been reported.

Inadvertent cardiac phlebography

We are reporting a case of a 80-year-old lady with effort angina who underwent coronary angiography through the right radial artery, using a dedicated radial multipurpose 5 French Optitorque Tiger catheter. The catheter was advanced into the left ventricle and a left ventriculogram was obtained, while the catheter appeared optimally placed at the centre of the ventricle and the pressure waveform was normal. A large posterior interventricular vein draining into the right atrium was opacified, presumably because the catheter's end hole inadvertently cannulated an endocardial opening of a small thebesian vein, with subsequent retrograde filling of the epicardial vein. Our case suggests that caution is needed when a dedicated radial catheter with both an end-hole and a side hole is used for a ventriculogram, as a normal left ventricular pressure waveform does not exclude malposition of the end-hole against the ventricular wall.

<i>In Vitro</i>Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels

Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.