Acute kidney injury following orthotopic liver transplantation: incidence, risk factors, and effects on patient and graft outcomes.

BACKGROUND: Liver transplant recipients frequently develop acute kidney injury (AKI), but the predisposing factors and long-term consequences of AKI are not well understood. The aims of this study were to identify predisposing factors for early post-transplant AKI and the impact of AKI on patient and graft survival and to construct a model to predict AKI using clinical variables. METHODS: In this 5-year retrospective study, we analysed clinical and laboratory data from 424 liver transplant recipients from our centre. RESULTS: By 72 h post-transplant, 221 patients (52%) had developed AKI [according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria]. Predisposing factors for development of AKI were female sex, weight (>100 kg), severity of liver disease (Child-Pugh score), pre-existing diabetes mellitus, number of units of blood or fresh frozen plasma transfused during surgery, and non-alcoholic steatohepatitis as the aetiology of end-stage liver disease (P≤0.05). Notably, preoperative serum creatinine (SCr) was not a significant predisposing factor. After fitting a forward stepwise regression model, female sex, weight >100 kg, high Child-Pugh score, and diabetes remained significantly associated with the development of AKI within 72 h (P≤0.05). The area under the receiver operator characteristic curve for the final model was 0.71. The incidence of new chronic kidney disease and requirement for dialysis at 3 months and 1 yr post-transplant were significantly higher among patients who developed AKI. CONCLUSIONS: Development of AKI within the first 72 h after transplant impacted short-term and long-term graft survival.

NOD2/CARD15 variants in Malaysian patients with sporadic colorectal cancer.

Colorectal cancer (CRC) is one of the most common types of cancer in both developed and developing countries. This disease is triggered by and progresses via the sequential accumulation of multiple genetic alterations. In addition, the interaction between low-penetrance genes and environmental factors can also increase the risk of developing CRC. Since inflammatory bowel diseases (IBDs) are one of the predisposing factors for CRC, IBD-related genes might, to a certain extent, be associated with cancer initiation. The nucleotide oligomerization domain 2/caspase activating recruitment domain 15 gene (NOD2/CARD15) is the most well-established gene to be associated with increased susceptibility to Crohn's disease. Thus, various studies have been performed to investigate the potential contribution of this gene to CRC risk. In this study, we aimed to determine the frequency of the Arg702Trp, Gly908Arg, 3020insC, Pro268Ser, and JW1 variants of NOD2/CARD15, and to investigate their association with CRC susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this study. Subsequently, real-time polymerase chain reaction with TaqMan was performed for the genotyping of these NOD2/ CARD15 variants. None of the NOD2/CARD15 variants was statistically associated to CRC susceptibility in our Malaysian population. Our findings were remarkably similar to those of other Asian cohorts, which indicated that these NOD2/CARD15 variants exhibit genetic heterogeneity between Caucasian and Asian populations.

Association between EGF and VEGF functional polymorphisms and sporadic colorectal cancer in the Malaysian population.

Growth factors are polypeptides that are critical for the initiation, progression, and metastasis of cancer. Most tumor cells are capable of synthesizing particular growth factors leading to constitutive pathway activation in these cells through autocrine signaling. Epidermal growth factor (EGF) is a potent mitogenic peptide that exerts direct effects on the proliferation and differentiation of tumor cells in carcinogenesis. By contrast, vascular endothelial growth factor (VEGF) is vital for the invasion and metastasis of neoplasms through the formation of new blood vessels from mature endothelial cells. In this study, we investigated the association between functional polymorphisms of both the EGF and VEGF genes and colorectal cancer (CRC) susceptibility. A total of 130 CRC patients and 212 healthy controls were recruited for this case-control study. Genotyping of genetic variants was conducted via real-time polymerase chain reaction (PCR) amplification with allele-specific TaqMan probes. None of the genotypes of the EGF +61 A>G and VEGF +936 C>T variants was significantly associated with CRC susceptibility among the Malaysian subjects evaluated (P > 0.05). The observed frequency distributions of the EGF +61 A>G polymorphism genotypes showed ethnic heterogeneity, which was not the case for the VEGF +936 C>T genotypes. In conclusion, no positive correlation between these functional polymorphisms and CRC risk was found in this Malaysian population. Studies of the EGF and VEGF genes and CRC susceptibility are scarce, and the results reported thus far differ from one population to another. Hence, more replication studies are warranted before any firm conclusions can be made.

Lack of association between TYK2 and STAT3 genes and Crohn's disease in the Malaysian population.

This study aimed to investigate the potential association of TYK2 and STAT3 genes with the susceptibility to Crohn's disease (CD) among Malaysians. DNA samples were obtained from 80 CD patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism methods were employed for genotyping, followed by statistical analysis. In our current study, none of the single nucleotide polymorphisms of either TYK2 or STAT3 was statistically associated with the susceptibility to CD in our local population (P > 0.05). In contrast, there was a statistically significant association between the G/G homozygotes of the STAT3 rs2293152 and the healthy control group (χ(2) = 6.229, P < 0.05). In conclusion, our study does not support the role of the TYK2 and STAT3 genes influencing CD susceptibility.

Pulmonary thromboembolism during adult liver transplantation: incidence, clinical presentation, outcome, risk factors, and diagnostic predictors.

BACKGROUND: Intraoperative pulmonary thromboembolism (PTE) is an often overlooked cause of mortality during adult liver transplantation (LT) with diagnostic challenge. The goals of this study were to investigate the incidence, clinical presentation, and outcome of PTE and to identify risk factors or diagnostic predictors for PTE. METHODS: Four hundred and ninety-five consecutive, isolated, deceased donor LTs performed in an institution for a 3 yr period (2004-6) were analysed. The standard technique was a piggyback method with veno-venous bypass without prophylactic anti-fibrinolytics. The clinical diagnosis of PTE was made with (i) acute cor pulmonale, and (ii) identification of blood clots in the pulmonary artery or observation of acute right heart pressure overload with or without intracardiac clots with transoesophageal echocardiography. RESULTS: The incidence of PTE was 4.0% (20 cases); cardiac arrest preceded the diagnosis of PTE [75% (15)] and PTE occurred during the neo-hepatic phase [85% (17)], especially within 30 min after graft reperfusion [70% (14)]. Operative and 60 day mortalities of patients with PTE were higher (P<0.001) than those without PTE (30% vs 0.8% and 45% vs 6.5%). Comparison of perioperative data between the PTE group (n=20) and the non-PTE group (n=475) revealed cardiac arrest and flat-line thromboelastography in three channels (natural, amicar, and protamine) at 5 min after graft reperfusion as the most significant risk factors or diagnostic predictors for PTE with an odds ratio of 154.32 [95% confidence interval (CI): 44.82-531.4] and 49.44 (CI: 15.6-156.57), respectively. CONCLUSIONS: These findings confirmed clinical significance of PTE during adult LT and suggested the possibility of predicting this devastating complication.

Central venous thrombosis and perioperative vascular access in adult intestinal transplantation.

BACKGROUND: Venous access is crucial in intestinal transplantation, but a thrombosed venous system may prevent the use of central veins of the upper body. The incidence of venous thrombosis and the necessity to perform alternative vascular access (AVA) in intestinal transplant recipients have not been fully investigated. METHODS: Records of adult patients who underwent intestinal transplantation between January 1, 2001, and December 31, 2009, were reviewed. Contrast venography was performed as pre-transplantation screening. Vascular accesses at the transplantation were categorized as I (percutaneous line via the upper body veins), II (percutaneous line via the lower body veins), and III (vascular accesses secured surgically, with interventional radiology, or using non-venous sites). Categories II and III were defined as AVA. Risk factors for central venous thrombosis and those for requiring AVA were analysed, respectively. RESULTS: Among 173 patients, central venous obstruction or stenosis (<50% of normal diameter) was found in 82% (141 patients). AVA was required in 4.6% (eight patients: four in each category II and III). Large-bore infusion lines were placed via the femoral arteries in all category III patients without complications. Existing inferior vena cava filter and hypercoagulable states were identified as the risk factors for the use of AVA, but not for central venous thrombosis. Outcomes of patients who underwent AVA were similar to those of patients without AVA. CONCLUSIONS: The majority of adult patients undergoing intestinal transplantation had at least one central venous stenosis or obstruction. The recipient outcomes were comparable when either standard vascular access or AVA was used for transplantation.

Co-inheritance of variants/mutations in Malaysian patients with Crohn's disease.

Crohn's disease is a chronic, relapsing inflammatory bowel disease; it affects the mucosa and deeper layers of the digestive wall. Two Crohn's disease patients who carried the JW1 variant and two patients who carried the SNP5 variant were investigated for other co-inherited polymorphisms that could influence Crohn's disease development. Based on the sequencing results, a homozygous 5'-UTR-59 G to A variant in exon 1 (SNP6) was observed in a patient who carried SNP5, while a heterozygous SNP6 variant was detected in the other patient who carried SNP5. No other associated mutations or polymorphisms were detected in the two patients who carried the JW1 variant of the CARD15/NOD2 gene.

Imaging findings of extensive splenic infarction after cyanoacrylate injection for gastric varices--a case report.

Endoscopic injection of N-Butyl-2-cyanoacrylate is a widely accepted treatment for esophagogastric varices. This procedure is commonly associated with minor complications which include transient pyrexia and abdominal discomfort. Serious vascular complications secondary to systemic embolization of cyanoacrylate have rarely been reported. We describe the CT findings of extensive splenic infarction in a patient following cyanoacrylate injection for gastric varices.

Chemoprevention of colorectal cancer with nonsteroidal anti-inflammatory drugs.

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti-inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)-2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.

Colorectal cancer in Asians: a demographic and anatomic survey in Malaysian patients undergoing colonoscopy.

BACKGROUND: Colorectal cancer is one of the most common forms of gastrointestinal cancer in the world today. In the Asia-Pacific area, it is the fastest emerging gastrointestinal cancer. AIM: To determine the basic demographic features of patients with colorectal cancer and the anatomic distribution and characteristics of the tumour in a local Asian population. METHODS: We conducted a review of consecutive patients who had undergone colonoscopy from 1999 to 2003 at the University of Malaya Medical Center, Kuala Lumpur, Malaysia. RESULTS: Analysis was carried out on 3404 patients who underwent colonoscopy. A total of 228 patients (7%) were diagnosed with carcinoma. The mean age of diagnosis (+/-s.d.) was 64.4 +/- 13.1 years. The male to female ratio was 1.15. Polyps were noted in 470 patients (14%). Polyps detected concomitantly with a colorectal cancer were noted in 55 patients (2%). Four patients (0.1%) were diagnosed to have familial adenomatous polyposis coli. Of the 228 patients 209 (92%) had tumours at only one site whereas 19 (8%) had synchronous lesions. Tumours were mainly left sided [198 of 248 patients (80%)] with the majority located in the recto-sigmoid region. Detailed records of treatment were available only in 176 patients. A total of 147 of 176 patients (84%) underwent surgery and 50 (28%) also received adjuvant or palliative chemotherapy (28%). Seven of 154 patients (5%) were diagnosed to have stage A cancers, 64 (42%), stage B, 23 (15%), stage C and 60 (39%), stage D. Multivariate analysis using multiple logistic regression analysis showed that age > or =65 years (OR = 1.78; 95% CI: 1.35- 2.36) and Malay (OR = 2.09; 95% CI: 1.30-3.35) and Chinese (OR = 1.77; 95% CI: 1.77-2.69) race were significant independent predictive factors for colorectal cancer. CONCLUSIONS: The demography of colorectal cancer is different from western patients. Tumours were mainly left sided in our patients. However, no differences in anatomic location were found between races, men and women and younger and older age groups. Colorectal cancer presented in an advanced stage in the majority of patients.

Orthotopic liver transplantation in patients over 60 years old.

A retrospective examination was performed, including a case control study, of 40 patients aged 60 years and over who underwent liver transplantation at King's College Hospital, London, UK, between 1988 and September 1993. There was no significant difference between elderly patients and younger patients in preoperative condition, intraoperative interventions, or outcome assessed by survival, complication rate, and duration of stay on the intensive care unit. The only significant difference between age groups was the median length of hospital stay, which was 24 days for the elderly versus 20 days for younger patients. We conclude that age up to 70 years should not be a barrier to liver transplantation.

Analysis of major complications associated with arterial catheterisation.

INTRODUCTION: Arterial catheterisation is used for continuous haemodynamic monitoring in patients undergoing surgery and in critical care units. Although it is considered a safe procedure, a major complication such as arterial occlusion and limb gangrene can occur. OBJECTIVE: To determine the incidence, outcome and potential to avoid complications associated with arterial catheterisation. METHODS: The number of arterial catheterisation was determined using an anaesthesiology and critical care medicine billing database over a period of 4 years (1 January 2003 to 31 December 2006). Possible major complications were identified from two hospital databases; all identified charts were screened and then reviewed by an expert panel that determined causation. A major complication was defined as requiring operative intervention and/or resulting in permanent harm. RESULTS: 15 (0.084%) major complications were identified among 17 840 instances of arterial catheterisation insertions. Of 15 arterial catheterisations, nine were performed in the operating room and six in the intensive care unit. Nine patients suffered ischaemic injury, which progressed to gangrene in three patients. Three patients developed haematoma that required surgical evacuation; two of these required vascular repair. One patient had compartment syndrome requiring fasciotomy and two patients had sheared catheter fragments that needed to be removed. All 15 patients had multiple comorbidities, and those in the operating room had an American Society of Anesthesiologists score of >or=3. Seven (46.6%) had arterial catheterisation done under emergent circumstances. Six (40%) died during hospitalisation because of complications unrelated to arterial catheterisation. CONCLUSION: Arterial catheterisation had a very low rate of major complications. They seem associated with high severity of illness and emergency surgery.

Demography and clinical course of ulcerative colitis in a multiracial Asian population: a nationwide study from Malaysia.

OBJECTIVE: To establish the clinical course of ulcerative colitis (UC) in the Malaysian population, comparing the three major ethnic groups: Malay, Chinese and Indian. METHODS: Patients who were diagnosed with UC from seven major medical referral centers in Malaysia were recruited. Their baseline characteristics, and the extent of the disease, its clinical course and complications were recorded. RESULTS: A total of 118 patients was included. The extent of disease was as follows: proctitis alone in 22 (18.6%), sigmoid colon in 23 (19.5%), descending colon in 16 (13.6%), transverse colon in 11 (9.3%), ascending colon and pancolitis 46 (39%). Most patients had chronic intermittent disease. Extra-intestinal complications were seen in 27 (22.9%) patients and fulminant colitis was seen in four (3.4%). None developed colorectal cancer. The overall cumulative colectomy rates at 1, 5 and 10 years were 3.4% (CI: 0.9-8.5), 5.9% (CI: 1.9-13.2) and 15.6% (CI: 6.5-29.4), respectively. There was a higher prevalence of extra-intestinal manifestations and a trend towards more extensive disease among Indian patients. However, no significant differences were seen in the age of onset, the severity of disease (fulminant colitis, refractory disease) and the colectomy rate. CONCLUSION: As in developed countries, most of our patients have a remitting and relapsing pattern of disease but the clinical course appears to be milder, with lower rates of colectomies. There are differences in clinical presentation among the three major ethnic groups, with Indians having a higher prevalence of extra-intestinal manifestations and a trend towards more extensive disease.

Improved haemodynamic stability with administration of aprotinin during orthotopic liver transplantation.

In a placebo-controlled, double-blind study, we have investigated the hypothesis that patients for orthotopic liver transplantation (OLT) treated with high-dose aprotinin (serum concentrations > or = 200 kiu ml-1) show greater haemodynamic stability on graft reperfusion. We studied 55 adult patients presenting for OLT, and 52 were included in the analysis. The treatment and placebo groups were similar in patient characteristics. The anaesthetic regimen used was standardized, and veno-venous bypass were used in all patients. Cardiac output measurements and haemodynamic profiles were recorded at intervals throughout anaesthesia and surgery. Arterial and mixed venous oxygen saturations were measured by co-oximetry. Derived variables were measured using standard formulae. Aprotinin treated patients had greater values for systemic vascular resistance on reperfusion, with a lesser cardiac index and calculated oxygen delivery. Oxygen consumption, however, was significantly greater, despite reduced delivery.

Effects of intraoperative N-acetylcysteine in orthotopic liver transplantation.

N-acetylcysteine (NAC) is an antioxidant agent which has been shown to benefit patients with fulminant hepatic failure. We have examined its effect in patients with chronic liver disease undergoing orthotopic liver transplantation by giving NAC during operation. In a prospective, randomized, double-blind, placebo-controlled study of 50 patients, NAC appeared to induce mild vasodilatation, improve oxygen delivery and consumption, and reduce base deficit, but data interpretation was difficult. There were no significant effects on mortality, morbidity or postoperative graft function.

The hyperventilation of cirrhosis: progesterone and estradiol effects.

Progesterone and estradiol are metabolized in the liver and are elevated in patients with cirrhosis. Progesterone stimulates ventilation by activating progesterone receptors in the central nervous system; estradiol may facilitate progesterone's actions by increasing progesterone receptors. This study evaluated whether progesterone and estradiol contribute to the respiratory alkalosis common in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels were obtained in 50 patients with cirrhosis. Multiple linear regression revealed a statistically significant correlation between PaCO2 and progesterone and estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or = 30 mm Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of magnitude lower than those associated with hyperventilation in pregnant patients, the increased ventilatory effect may be because of the altered blood-brain barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to contribute to the hyperventilation in cirrhotic patients.