Outcome of Liver Transplantation in Hepatocellular Carcinoma Patients at Siriraj Hospital.

BACKGROUND: Liver transplantation (LT) is one of the standard treatments for hepatocellular carcinoma (HCC), and the outcomes have become better after introduction of strict patient selection, such as the Milan criteria. However, several expanded criteria, such as the University of California San Francisco (UCSF) criteria, have demonstrated similar survival outcomes. The aim of this study was to verify survival outcomes of LT for HCC at Siriraj Hospital. METHODS: Sixty-three patients diagnosed with HCC who underwent cadaveric LT at Siriraj Hospital from 2002 to 2011 were included. All patients' characteristics, blood chemistries, size and number of tumors, bridging therapy, and survival and recurrence data were retrospectively reviewed and analyzed. RESULTS: Nearly all (62 patients, 98.4%) fulfilled the Milan criteria based on preoperative imaging. Explant pathology revealed that 40 patients (63.5%) were within Milan criteria and 50 patients (83%) within UCSF criteria. Demographic data, clinical laboratory, and bridging therapy were similar in patients within and outside both Milan and UCSF criteria. The 1-, 3-, and 5-year survival rates of patients within Milan were 85%, 75%, and 67.5%, and of those outside Milan were 69.6%, 52.2%, 52.2%, respectively (P = .25). Interestingly, with the use of the UCSF criteria, the 1-, 3-, and 5-year survival rates of patients within UCSF were significantly better than of those outside UCSF (84%, 76%, and 70% vs 61.5%, 30.8%, and 30.8%, respectively; P = .01). CONCLUSIONS: Outcome of LT in HCC patients within Milan criteria demonstrated good long-term survival. However, providing the opportunity for HCC patients by expanding from Milan to UCSF criteria revealed similar outcomes.

Correlation of Hematocrit and Tacrolimus Level in Liver Transplant Recipients.

BACKGROUND: Tacrolimus is the most widely used immunosuppressive drug after liver transplantation. Whole blood tacrolimus level is used for drug monitoring. Because of strong uptake by erythrocytes (95% to 98%), hematocrit level is an important factor for evaluation whole blood tacrolimus level. There has been no formula to calculate the effect of hematocrit on the whole blood tacrolimus level. The aim of this study is to evaluate the effect of hematocrit on the whole blood tacrolimus level. METHODS: Twenty-five patients were included in this study. Blood samples during routine follow-up were used. All patients received tacrolimus for more than 30 days after liver transplantation. Approximately half of the plasma was removed. Blood samples were remixed and remeasured for hematocrit and whole blood tacrolimus levels. Pearson correlation and linear regression were performed to generate a formula for corrected tacrolimus level. RESULTS: Thirteen male and 12 female patients participated in this study. There was a significant positive correlation between hematocrit ratio and tacrolimus ratio (r = 0.765, r(2) = 0.585, P < .001). The pattern of linear relationship between hematocrit ratio and tacrolimus ratio is defined by the regression equation, and the formula to correct tacrolimus level at hematocrit 40% is as follows: [Formula: see text] CONCLUSION: Hematocrit has a significant effect on tacrolimus level. Better dose adjustment for patients should include the consideration of hematocrit levels. Further studies are required to validate this formula and clinical significance.

Systematic Pharmaceutical Educational Approach to Enhance Drug Adherence in Liver Transplant Recipients.

BACKGROUND: Drug adherence is one of the most important factors determining graft and patient survivals after liver transplantation. A systematic pharmaceutical educational approach has been implemented to improve adherence in immunosuppressive drugs therapy at Siriraj Hospital. METHODS: This study was a single-center cross-sectional study of liver transplant patients who received pharmaceutical care from transplant pharmacists. The clinical pharmacy services, including medication review to emphasize patients' knowledge and awareness of immunosuppressive and general drug therapies with the use of various tools, were used to educate the patients. Drug-related problems (DRPs) and pre- and post-transplantation educational tests (divided into 3 parts: immunosuppressants [12 points], drug monitoring [6 points], and general drugs [2 points]) were analyzed. RESULTS: From October 2012 to September 2014, a total of 50 liver transplant recipients (86 visits) were enrolled. After the systematic pharmaceutical educational program, the average total score of post-transplantation educational test improved from 3.48 to 13.30 (P < .001). Likewise, the mean scores of all 3 parts significantly increased (part I: 2.28 vs 8.18 [P < .001]; part II: 0.75 vs 3.63 (P < .001); and part III: 0.46 vs 1.50 [P < .001]). The incidences of major DRPs, nonadherence, and adverse drug reactions were 8%, 4%, and 2%, respectively. CONCLUSIONS: A systematic pharmaceutical educational approach can significantly improve patients' knowledge and awareness concerning immunosuppressive drug usage.

Immunosuppressive Medication Adherence in Liver Transplant Recipients.

BACKGROUND: Immunosuppressive medication is one of the pivotal factors in the outcome of liver transplant patients. Nonadherence to immunosuppressive therapy is a common problem after transplantation and affects graft and patient survival. This study aimed to assess immunosuppressive medication adherence in liver transplant recipients. METHODS: Liver transplant recipients who underwent the Siriraj-Support Medication Adherence in Organ Transplantation (S-SMAOT) program were included in this cross-sectional study. Immunosuppressive medication adherence was assessed with the use of the Immunosuppressive Therapy Adherence Scale (ITAS, which is scored from 0 to 12; very poor to excellence adherence). The correlations between ITAS scores and the clinical profiles of the patients, duration after transplantation, and transplant educational scores post-test were also analyzed. RESULTS: From October 2012 to September 2014, a total of 50 liver transplant recipients (86 visits) were enrolled in this study. The ratio of male to female patients was 48:52. The proportions of patients with ITAS scores of 12, 10-11, and 0-9 were 82.6%, 16.3% and 1.2%, respectively. ITAS score was significantly correlated with the duration after transplantation (P < .001) and the educational scores (P = .009). CONCLUSIONS: Consistent assessment of patients' immunosuppressive medication adherence is essential to avoid problems of noncompliance and to improve the outcome after liver transplantation. The S-SMAOT program was an effective approach to significantly improve the medication adherence in liver transplant recipients.

Outcomes of orthotopic liver transplantation in non-malignant end-stage liver diseases.

BACKGROUND: Orthotopic liver transplantation (OLT) is an effective treatment for patients who have end-stage liver disease. The aim of this study is to compare outcomes of OLT in fulminant hepatic failure (FHF) and non-fulminant hepatic failure (non-FHF) patients. METHODS: A retrospective review of adult patients who underwent OLT for non-malignant end-stage liver diseases between 2002 and 2011 at Siriraj Hospital was performed. All explanted liver histopathology results were reviewed. The clinical factors and overall results of OLT were analyzed. RESULTS: Of the 137 patients, 72 patients had non-malignant diagnoses. Eleven patients were diagnosed with FHF, whereas 61 patients were in the non-FHF group. The most common indication for liver transplantation was chronic viral hepatitis. One- and 5-year survival rates (95% confidence interval) in the FHF group were 91% (51%-99%) and 91% (51%-99%), respectively, whereas those in the non-FHF group were 74% (61%-83%) and 66% (52%-77%), respectively. Multivariate cox regression analysis revealed no statistically significant difference of survival between both groups (P = .34). CONCLUSIONS: The post-OLT outcomes in non-malignant patients were comparable between FHF and non-FHF groups in terms of survival. OLT remains the only therapeutic option for the FHF patients.

Renal dysfunction after orthotopic liver transplantation.

BACKGROUND: Identification of risk factors of acute renal failure (ARF) after orthotopic liver transplantation (OLT) may avoid the development and attenuate the impact on patient outcome. Therefore, the incidence and risk factors of ARF after OLT at Siriraj Hospital were analyzed. METHODS: The study was retrospectively analyzed from the OLT patients at the Siriraj Hospital between January 2002 and December 2009. ARF was defined as an increased in serum creatinine level more than 1.5 times within the first week postoperation compared with the preoperative level. RESULTS: A total of 81 liver transplant patients were analyzed. The mean age was 52.45 years (range, 22 to 71) and there were 25 women (30.86%) and 56 men (69.14%). Indications for OLT were end-stage liver cirrhosis (n = 43, 53.09%), hepatocellular carcinoma (n = 36, 44.44%), and fulminant hepatic failure (n = 2, 2.47%). Fifty-eight patients (71.60%) developed ARF, and the perioperative mortality of these was 18.97%. The univariate analysis identified the presence of preoperative coagulopathy, prolonged intraoperative hypotension, more blood loss, and postoperative hypotension as the risk factors of ARF. By the multivariate analysis, prolonged intraoperative hypotension more than 30 minutes and presence of postoperative hypotension were the independent risk factors of ARF. During the intraoperative and postoperative periods, ARF group required more blood and blood components transfusion, longer intensive care unit stay, and higher in-hospital mortality. Seven patients (12.07%) in the ARF group required postoperative renal replacement therapy. Four patients (9.52%) developed chronic renal failure, and one of them required long-term hemodialysis. CONCLUSIONS: ARF was a common complication after OLT, which caused increased morbidity and mortality. Although some patients required dialysis, most of them recovered normal renal function. Prolonged intraoperative hypotension and presence of postoperative hypotension were the independent risk factors of ARF after OLT.

Analysis of donor risk factors associated with graft outcomes in orthotopic liver transplantation.

BACKGROUND: In orthotopic liver transplantation (OLT), the critical shortage of organ donors is the reason for accepting marginal donors. Although the outcome of OLT does not entirely seem to have been affected by the use of such donors identification of predictive risk factors is challenging. This study sought to identify significant risk factors associated with graft outcomes in our institute. METHODS: We retrospectively analyzed donor-associated factors for recipients who underwent liver transplantation from January 2002 to December 2009 for displaying primary dysfunction (PDF) as primary nonfunction (PNF) and initial poor function (IPF). RESULTS: We examined 97 post-liver transplant patients (male:female 70:27) whose average age was 52.74 years. The majority of indications for OLT were hepatitis B and/or C cirrhosis, alcoholic cirrhosis, and hepatocellular carcinoma. The incidence of PDF was 31.9% (31/97) including 7.2% PNF (7/97) and 24.7% IPF (24/97), versus 68.1% (66/97) with immediate function. The donors last serum alanine aminotransferase value being more than 65 IU/L was the only risk factor for poor graft function (P=.034). Donor peak and last serum sodium were potential risk factors. CONCLUSION: Although many factors including a high serum sodium level are associated with a marginal liver graft, Last donor alanine aminotransferase level was the only significant factor that predicted the PDF.

Recipient and perioperative risk factors associated with liver transplant graft outcomes.

BACKGROUND: Orthotopic liver transplantation (OLT) is currently considered to be the ultimate form of therapy for most patients with end-stage liver diseases. The identification of recipient and various perioperative factors that may affect the graft outcomes is critical. This study sought to analyze the preoperative and perioperative factors associated with graft outcomes in our institute. METHODS: This retrospective study of liver transplanted patients from January 2002 to December 2009 determined the incidence of 2 forms of primary dysfunction (PDF): Primary nonfunction (PNF) and initial poor function (IPF). RESULTS: The 97 posttransplant patients included in the study had an average age of 52.74 years. The majority of indications for OLT were hepatitis B and/or C cirrhosis, alcoholic cirrhosis, and hepatocellular carcinoma. The incidence of PDF was 31.9% (31/97) with 7.2% (7/97) PNF and 24.7% (24/97) IPF. Additionally, we observed 68.1% (66/97) to display immediate function (IF). Warm ischemic time (WIT) and operative time were significantly longer in the PDF compared with the IF group. The logistic regression model showed a WIT of >45 minutes to be a risk factor leading to PDF (odds ratio, 11.74; P<.05). An operative time of >6 hours and operative blood loss of >2 L were possible risk factors. CONCLUSION: Prolonged WIT (>45 minutes) was the only significant risk factor among other established parameters for graft function. Nevertheless, reduced operative times and blood loss may improve the outcomes of OLT.

Quality of life among liver transplantation patients.

BACKGROUND: Orthotopic liver transplantation (OLT) is the treatment of choice for end-stage disease. It offers a chance to return to an active and prolonged life. Recently, more attention is being paid to the health-related quality of life (HRQoL) of patients and their spouses or caregivers after OLT. The aim of this study was to analyze the pre- versus posttransplantation HRQoL of patients and their spouses or caregivers using generic and disease-specific health questionnaires. MATERIAL AND METHODS: The study was performed between October 2010 and January 2011 using the Short Form-36 (SF-36) and the Chronic Liver Disease Questionnaire (CLDQ) to evaluate the HRQoL. RESULTS: Posttransplantation patients (N=59, mean age 53.39 [range, 23 to 76] years, male 63.2%, female 36.8%) and their spouses and caregivers showed significantly better generic SF-36 HRQoL scores, namely, physical and social functioning, role limitations because of physical or emotional problems, bodily pain, vitality, as well as general and mental health compared with pretransplantation patients (N=57, mean age 54.56 (range, 22 to 69) years, male 71.2%, female 28.8%). Similarly, the posttransplantation group showed significantly improved CLDQ scores in all domains: fatigue, activity, abdominal symptoms, systemic symptoms, emotional function, and worry. CONCLUSION: OLT improved HRQoL of end-stage liver patients and their spouses or caregivers.

The 37-year kidney transplantation experience at Siriraj Hospital.

With 37-years of experience, a total of 801 kidney transplantations (59.4% were deceased donors and 40.6% were living donors) performed at Siriraj hospital were reported. The point system parallel to OPTN/UNOS for waitlists was utilized. Most of the recipients of deceased donor kidney transplantations had 3 HLA mismatches. Due to the point allocation system, none of them had 6 HLA mismatches. Extended criteria donor comprised 7.8% of all deceased donors. Mean duration of dialysis prior to deceased donor transplant was 53 +/- 34 months. Delayed graft function (DGF) was found in 54% of deceased donor kidney transplantation and resulted in significantly higher rate of 1 year biopsy-proven acute rejection, longer duration of kidney transplant admission, higher admission cost and lower patient survival compared to those with immediate graft function. Most of living donor kidney transplant recipient had 1 haplotype match. Mean donor age was 35.9 +/- 9.8 years. 95.6% of the recipients were on hemodialysis prior to transplantation. The current standard regimen includes calcineurin inhibitor, Mycophenolic acid and prednisolone. Interleukin-2 receptor monoclonal antibody has been used in the high immunological risk or high risk for DGF recipients that were 50% of the recipients. There was no statistically significant difference in the biopsy-proven acute rejection (BPAR) free survival between deceased and living donor transplantation. Proportion of cases with the diagnosis of acute rejection according to Banff 2007 classification is as follows: 32.4% acute cellular rejection (ACR), 39.4% antibody-mediated rejection (AMR) and 21.1% mixed cellular and antibody-mediated rejection. Seventy two patients, 35 deceased donor and 37 living donor kidney transplant recipients, had biopsy-proven glomerular disease after transplantation which IgA nephropathy is the most common form of glomerulonephritis. Median graft survival was 7.6 and 13.2 years and median patient survival was 12.1 and 15.5 years for recipient of deceased and living donor transplant respectively. The follow up program of living donors was introduced in 2003 and there were not any donors who required renal replacement therapy.

The minimal flush volume for washout of preservation fluid in liver transplantation.

OBJECTIVES: Organ preservation is one of the important steps that predicts the patient outcome. However, after revascularization, the high concentration of potassium that influxes into the circulation might cause immediate postreperfusion hyperkalemia. To prevent this complication, the portal vein has been washed out with flush fluid to remove preservation fluid before reperfusion. Up to now, it has not been established what exact amount volume of albumin provides washout of the UW solution. METHODS: Eleven of 20 patients who underwent orthotopic liver transplantation (OLT) between December, 2003, and June, 2005, were enrolled in this study. OLT was performed following the standard technique. Five percent albumin (1000 mL) was flushed through the portal vein canula before reperfusion of the donor liver. Every 100 mL of flush fluid effluent was collected from an incomplete infrahepatic inferior vena cava anastomosis for electrolyte measurement. The 10 flushed fluid samples were measured for potassium concentration. Mean arterial pressure was monitored preoperatively, at 1-minute intervals after reperfusion and at 60 minutes after reperfusion. RESULTS: We observed that 61.5% of potassium was removed after only 100 mL of flush fluid, and 90.8% after 500 mL. Only one patient in this study had an effluent potassium reduction that did not achieved 90% after 500- or 1000-mL flush. However, this patient did not develop either postreperfusion syndrome or hyperkalemia. One patient did experience postreperfusion hyperkalemia (6.20 mEq) with severe hypothermia and cardiac arrest. Five patients had stable hemodynamic profiles and five patients, transient, reversible hypotension without postreperfusion hyperkalemia. DISCUSSION AND CONCLUSIONS: We propose that the minimal flush volume for washout of preservation fluid in liver transplantation is 500 mL, to reduce the risk of postreperfusion syndrome and hyperkalemia.

The effect of N(G)-monomethyl-L-arginine and tamoxifen on nitric oxide production in breast cancer cells stimulated by oestrogen and progesterone.

OBJECTIVE: To examine the capacity of oestrogen, or progesterone, or both to elicit the release of nitric oxide (NO) from T47D breast cancer cells in vitro. DESIGN: Prospective, longitudinal, controlled in vitro experiment. SETTING: University Medical School, United Kingdom. MATERIAL AND INTERVENTIONS: T47D breast cancer cells were stimulated by micromolar to picomolar doses of 17beta-oestradiol, or progesterone, or both, with or without inhibition of NO or tamoxifen at 24 and 48 hours. MAIN OUTCOME MEASURES: Concentration of NO metabolites (nitrite + nitrate) in the culture medium measured by chemiluminescence. RESULTS: Both hormones dose-dependently increased the proliferation of T47D without toxic effects over the range 10(-12)-10(-6) M. Both stimulated NO production at 24 hours, micomolar doses producing a pronounced (2-4 fold) increase in the concentration of NO metabolites in culture medium (p = 0.002 and p < 0.001 for oestradiol and progesterone, respectively). By contrast, incubation with hormones for 48 hours had little effect on the concentrations of NO metabolites. NO production induced by hormones was completely inhibited by the NO synthesis inhibitor N(G)-monomethyl-L-arginine (10(-5)-10(-3) M) and by tamoxifen (10(-8)-10(-4) M) (p < 0.001 in each case). CONCLUSIONS: Oestrogen and progesterone have a role in stimulating NO production in T47D breast cancer cells. Inhibition of NO synthesis might be a novel therapeutic approach for reducing hormone-associated angiogenesis in breast cancer.

Genomic homogeneity in fibrolamellar carcinomas.

BACKGROUND: Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC) with distinctive clinical and histological features. To date there have been few studies on the genotypic aspects of FLC and no previous attempts have been made to use the arbitrarily primed-polymerase chain reaction (AP-PCR) technique to detect genetic alterations in this disease. AIM: The aim of this study was to assess the degree of genomic heterogeneity of FLC using the AP-PCR technique. METHODS: A total of 50 tissue samples of primary and metastatic FLCs from seven patients were microdissected. AP-PCR amplification of each genomic DNA sample was carried out using two arbitrary primers. RESULTS: DNA fingerprints of the primary FLCs and all their metastatic lesions (both synchronous and metachronous disease) were identical in an individual patient. The fingerprints were different between tumours of different patients. No evidence of intratumour heterogeneity was observed. CONCLUSIONS: Such genomic homogeneity in FLCs may explain their indolent growth. The absence of clonal evolution, which is present in other tumours (particularly HCCs), may explain the distinct behaviour in this tumour. The tumorigenic pathway and degree of somatic genomic changes in this disease may be less complex than in HCC.

Laparoscopic resection of liver metastasis using a harmonic scalpel.

We report successful laparoscopic resection of a solitary liver metastasis from a colorectal carcinoma in an obese man, using a harmonic scalpel.

Non-random chromosomal rearrangements in pancreatic cancer cell lines identified by spectral karyotyping.

The molecular events involved in pancreatic cancer are becoming increasingly well characterized, with mutations in the dominant oncogene KRAS and the tumour suppressor genes TP53, CDKN2A and MADH4 being typically observed. However, other genetic abnormalities remain to be identified and molecular cytogenetics may be useful to detect chromosomal loci involved in recurrent rearrangements. We have used spectral karyotyping to characterize cytogenetic aberrations in a panel of 20 human pancreatic carcinoma cell lines and confirmed their identities by dual and triple color fluorescence in situ hybridization. The most common partial or whole-arm gains involved 5p, 7q, 12p, 1q, 7p, 5q, 9p, 9q and 11p. The most common partial or whole-arm losses affected 9p, 11q, 18q, 3p, 2q and 1p, as well as the short arms of the acrocentric chromosomes. Spectral karyotyping allowed us to identify a number of recurrent structural aberrations, all of them unbalanced: most frequently i(5)(p10), del(11)(q23), i(12)(p10), i(1)(q10), del(7)(q22) and del(10)(p11). Spectral karyotyping mapped the complex aberrations occurring in pancreatic cancer cell lines and identified non-random patterns of chromosomal rearrangement. This comprehensive characterization should be useful to direct future investigation. The observation that loss at 11q and gains at 5p with i(5)(p10) and 12p with i(12)(p10) are more frequent changes than previously reported would justify more intensive investigation of these chromosomal regions.

Laser-assisted microdissection: applications in molecular pathology.

Tissue microdissection is potentially one of the most useful techniques in molecular pathology. Laser-assisted microdissection has been developed to procure precisely the cells of interest in a tissue specimen, in a rapid and practical manner. Together with multiplex molecular approaches, it is now feasible to study genetic alterations and isolate genes and proteins in defined cell populations from complex normal and diseased tissues. The fundamental advantage of this technique is the possibility of capturing single cells from which high-quality DNA and mRNA can be isolated for analysis of sequence and quantitation of expression. Moreover, the integration of laser-assisted microdissection and proteomic analysis could identify novel protein markers for disease. The advent of laser-assisted microdissection is likely to have a profound impact on molecular pathology.

Evolution of genetic abnormalities in hepatocellular carcinomas demonstrated by DNA fingerprinting.

Hepatocellular carcinomas (HCC) often contain subpopulations of cells showing heterogeneous differentiation within each tumour. The majority of HCCs first appear as well-differentiated lesions and proliferate with gradual dedifferentiation. The present study was designed to investigate the clonal diversity which is seen with progression in neoplasms. The degree of genomic heterogeneity of HCC nodules was assessed using the arbitrarily primed-polymerase chain reaction technique. Two or more sectors of 31 HCC nodules were needle-microdissected and amplified with two different arbitrary primers in appropriate conditions. In every HCC less than 6 mm in diameter (n=18, range 3-6 mm, mean diameter 4.7 mm), all sectors of each of these lesions had the same DNA fingerprint. All HCC nodules greater than 6 mm diameter (n=13, range 7-30 mm, mean diameter 15.4 mm) showed distinct DNA fingerprints in each sector sampled (p< 0. 05, compared with size less than 6 mm in diameter). When synchronous HCCs were present, no two tumour nodules had the same DNA fingerprint. These results suggest that a process of clonal evolution occurs in expanding HCC, with neoplasms more than 6 mm in diameter developing as multiple clones. The advent of laser capture microdissection technology makes such analysis much more rapid and easily applied. Studies of clonality in HCCs, including borderline cases, are made possible by the combination of these novel techniques.

Genomic heterogeneity in synchronous hepatocellular carcinomas.

BACKGROUND: Hepatocellular carcinoma (HCC) arising in cirrhosis is frequently multifocal. Whether HCC develops monoclonally or multiclonally is an unresolved question. Of the multiple tumour nodules present in many patients, it has not been established whether the smaller lesions represent intrahepatic metastases or de novo cancers. AIMS: To assess the degree of genomic heterogeneity in synchronous HCCs in cirrhosis. METHODS: The arbitrarily primed polymerase chain reaction technique was utilised to compare the DNA fingerprint of HCCs and regenerative nodules (RNs) removed from cirrhotic explant livers. RESULTS: Polymorphic genomic heterogeneity was noted in 54 HCCs and 31 RNs microdissected. Even satellite nodules in close proximity within the same segment of the liver were found to have distinct genomic patterns. CONCLUSION: Such genomic heterogeneity in synchronous HCCs may explain poor patient survival after surgical resection. If the smaller tumours are de novo lesions rather than metastases (as these data suggest), then current concepts regarding liver resection as a curative treatment modality for HCC may require reassessment.

Molecular pattern of ductal pancreatic cancer.

Our understanding of the molecular pathology underlying the development and progression of ductal pancreatic cancer has been revolutionised during the last 5 years due to the spectacular development of novel molecular biological techniques. In the present article, we describe key molecular alterations of sporadic and inherited ductal pancreatic cancer. Overexpression of growth factors and growth factor receptors are present in a significant proportion of this tumour type. Mutation of the K-ras oncogene, and disruption of p53 or p16 tumour suppressor gene abrogates the control of the cyclin-dependent kinases (cdk) and retinoblastoma (Rb) gene pathway, causing continuous growth of the pancreatic tumour. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the inhibitory influence of the transforming growth factor beta signalling pathway. Lost or decreased expression of retinoid receptors and failure of telomerase activity may play a role in pancreatic carcinogenesis. Tumour-associated proteinases, matrix metalloproteinases and plasminogen activators are reported to be involved in pancreatic cancer invasion and metastasis. Furthermore, the cytogenetic changes in this cancer are summarised. This molecular pattern distinguishes pancreatic cancer from other epithelial tumours and represents a promising basis for the development of diagnostic and other clinical applications.

The potential role of intraoperative ultrasonography in the surgical treatment of hilar cholangiocarcinoma.

The role of intraoperative ultrasonography (IOU) in the surgical treatment of hilar cholangiocarcinoma was explored in twenty-two patients, 17 males and 5 females. The mean age was 55 years (range 36-78 years). Preoperative imaging studies included abdominal ultra-sonography and/or CT scan, and visceral angiography. Operations performed were segment III bypass in 18 patients, local resection of tumour in 2 and resection of tumour en bloc with left hepatectomy in 2. Interpretation of IOU in terms of vascular involvement by the tumour (as compared to angiography or operative findings) was correct in 21 patients; no vascular invasion in 20 and portal vein invasion in the remainder. One false negative result occurred in a patient whose IOU failed to show right hepatic artery encasement by the tumour. When compared to postoperative cholangiography or surgical specimen, IOU correctly demonstrated location and extent of the tumours in all but one patient who had incomplete tumour resection. IOU was also helpful in locating segment III duct for biliary bypass. The mean time used for IOU was 15.1 min (range 10-20 min.), and there was no procedure-related complication. When supplemented with operative exploration, IOU seems to be very useful in the assessment of the resectability of hilar cholangiocarcinoma.