Telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts

BACKGROUND: Pancreatic serous cystadenoma, mucinous cystic neoplasms, ductal adenocarcinoma with cystic change, and pseudocysts are a spectrum of pancreatic cystic lesions. Their management strategy and prognosis are extremely diverse. Imaging study, cytology, and analysis of the tumor markers of cyst fluid are not always reliable in differentiation of these disease entities. MATERIALS AND METHODS: Fifteen patients with pancreatic cystic neoplasms (including six mucinous cystadenocarcinomas, two mucinous cystic neoplasms with borderline malignancy, two mucinous cystadenomas, and five serous cystadenomas), 4 patients with pancreatic ductal adenocarcinomas with cystic change, and 10 patients with pseudocysts were studied. Echo-guided or computed tomography-guided biopsies of pancreatic cystic lesions and their normal counterparts were conducted on all patients prior to operation or other management. The specimens were assayed for telomerase activity by using TRAP (telomere repeat amplification protocol). The level of telomerase activity in each specimen was semiquantitated as strong, moderate, weak, and none. The final diagnoses were made from histopathological examination of surgically resected or biopsied specimens. The efficacy of telomerase activity as a tumor marker to predict malignancy of pancreatic cystic lesions was evaluated. RESULTS: Three of the four pancreatic ductal adenocarcinomas with cystic change had strong or moderate telomerase activity; four of the six mucinous cystadenocarcinomas had moderate or weak telomerase activity; one of the two mucinous cystadenomas with borderline malignancy had weak telomerase activity; and none of their normal counterparts had detectable telomerase activity. In contrast, none of the two mucinous cystadenomas, five serous cystadenomas, and 10 pseudocysts had detectable telomerase activity. Based on these results, the sensitivity of telomerase activity for prediction of malignancy or premalignancy of pancreatic cystic lesions was 67%, the specificity was 100%, and the positive and negative predictive values were 1.0 and 0.81, respectively. The overall accuracy was 86%. CONCLUSIONS: The differential expressions of telomerase activity have been detected specifically in malignant and premalignant pancreatic cystic tumors, but not in benign cystic neoplasms or pseudocysts. The implications of these results are that telomerase activation takes part in the malignant transformation of pancreatic cystic neoplasms and that telomerase activity is a useful marker to distinguish malignant pancreatic cystic tumors from benign neoplasms and pseudocysts.     

Percutaneous Placement of Self-expandable Metallic Biliary Stents in Malignant Extrahepatic Strictures: Indications of Transpapillary and Suprapapillary Methods

Objective

To compare the efficacy of suprapapillary and transpapillary methods of transhepatic biliary metallic stent placement in malignant biliary strictures and to specify the indications of each method applied.

Materials and Methods

Stents were placed in 59 patients. Strictures were categorized as type A (within 3 cm of the ampulla, n = 27), type B (over 3 cm from ampulla, n = 7), type C (within 3 cm of the bending portion, n = 9), or type D (over 3 cm above the bending portion, n=16). The stenting method was suprapapillary in 34 cases and transpapillary in 25. The rates of initial and long-term patency and of early recurrence were compared.

Results

Initial patency rates for the suprapapillary and transpapillary methods were 1/7 (14.3%) and 20/20 (100%) respectively for type A (p < 0.0001), 4/5 (80.0%) and 2/2 for type B, 3/7 (42.9%) and 2/2 for type C, and 15/16 (93.8%) and 0/0 for type D. Early recurrence rates were 7/30 (23.3%) using the suprapapillary method and 4/29 (13.8%) using the transpapillary method (p = 0.51). The long-term patency rate did not differ significantly according to either type (p = 0.37) or method (p = 0.62).

Conclusion

For good initial patency, the transpapillary method is recommended for strictures of the distal extrahepatic duct near the ampulla and just above the bending portion. Long-term patency is not influenced by the stenting method employed.     

Discordance between dipyridamole stress Tc-99m sestamibi SPECT and coronary angiography in patients with Kawasaki disease

BACKGROUND: Kawasaki disease is an acute vasculitis syndrome of unknown etiology that mainly affects the coronary arteries. The purpose of this study was to assess the agreement between dipyridamole stress technetium 99m sestamibi single photon emission computed tomography (SPECT) and coronary angiography in these patients. METHODS AND RESULTS: Forty-one consecutive patients (29 boys and 12 girls) who underwent coronary angiography were studied prospectively. Their ages at onset of the disease ranged from 2 months to 4.8 years (mean +/- SD, 1.9 +/- 1.3 years). Their ages at the time of the study ranged from 8 months to 15.3 years (6.2 +/- 4.4 years). The duration between symptom onset and the study ranged from 2 months to 12 years (4.3 +/- 4.0 years). All patients underwent dipyridamole stress Tc-99m sestamibi SPECT within 1 month of their angiographic studies. They were divided into 3 groups according to coronary angiography findings. Group A consisted of 2 patients (1 boy and 1 girl, aged 10.3 and 1.9 years, respectively) with coronary stenoses who also had aneurysms. Group B consisted of 10 patients (8 boys and 2 girls, aged 0.7-15.3 years [mean, 3.8 years]) with coronary aneurysms. Group C consisted of 29 patients (20 boys and 9 girls, aged 1.2-13.8 years [mean, 7 years]) with normal coronary angiograms. Two patients in group A (100%), 3 of 10 patients in group B (30%), and 19 of 29 patients in group C (65.5%) had myocardial perfusion defects. There was poor agreement between Tc-99m sestamibi SPECT and coronary angiography for detecting coronary stenoses (kappa = 0.07; P =.222) and aneurysms (kappa = -0.184; P =.158). CONCLUSION: Significant discordance exists between Tc-99m sestamibi SPECT and coronary angiography in patients with Kawasaki disease.     

Umbilical portion of recipient's left portal vein: a useful vascular conduit in dual living donor liver transplantation for the thrombosed portal vein.

We considered performing living donor liver transplantation (LDLT) in a larger-size recipient. When the recipient was large-sized, or when the donor liver was severely steatotic or had a right-to-left volume discrepancy. We devised dual living donor liver transplantation (DLDLT) to make up for graft size insufficiency and to secure the donor's safety. However, portal vein thrombosis (PVT) presented a challenge for DLDLT because of the need for intact right and left portal veins for the implantation of both liver grafts. Our 52-year-old male patient with hepatitis B cirrhosis had suffered from repeated esophageal and gastric variceal bleeding and underwent 2 trials of a transjugular intrahepatic portosystemic shunt (TIPS). He developed TIPS occlusion and PVT involving the area just above the spleno-mesenteric confluence to the right and left PV. Also, the right PV orifice was destructed and difficult to isolate because of severe periportal inflammation and neointima growth in the TIPS mesh. The patient's two sons were inadequate for donation because of right-to-left volume discrepancy. Therefore, DLDLT using 2 left lobes was necessary to compensate for graft-size insufficiency and to secure donor safety, and we substituted an intact umbilical portion of recipient's left PV for the destroyed right PV. The patient recovered well, and liver function has been normal for more than a year. In conclusion, the umbilical portion of recipient's left PV can be a useful vascular substitute for the reconstruction of a thrombosed main portal branch in DLDLT.     

BK virus infection in kidney transplant recipients

INTRODUCTION: Nephropathy associated with the polyomavirus type BK virus (BKV) has emerged as a cause of allograft failure linked to immunosuppressive regimens containing tacrolimus or mycophenolate mofetil (MMF). The outcome in BKV nephropathy is generally unfavorable, namely 50% of patients lose graft function. We herein report nine cases of BKV nephropathy after kidney transplantation. METHODS: From October 1998 to May 2003, 138 of 169 consecutive kidney transplant patients received tacrolimus-based immunosuppression, and 31 received cyclosporine-based immunosuppression. Additionally, 88.2% of the patients received mycophenolate mofetil (MMF). The diagnosis of BK infection was made by the presence of decoy cells in the urine and by allograft biopsy. RESULTS: There were nine cases of BKV nephropathy in kidney transplant recipients, an incidence of 5.3%. All patients with BKV nephropathy received tacrolimus, MMF, and steroids. The median time to diagnosis of BKV infection was 7.8 months after transplantation. All patients experienced an elevated serum creatinine, which stabilized or decreased in seven patients with altered or decreased immunosuppression. After a mean follow-up of 11.1 months, 2 (22.2%) of nine patients lost the graft. CONCLUSION: Because BKV nephropathy is a rare but serious complication after kidney transplantation, it should be included in the clinical differential of transplant dysfunction. In the absence of documented antiviral treatment, early diagnosis and judicious use of immunosuppressive agents is indicated to minimize the occurrence of BKV infection.     

Do patients with acute liver failure have a better chance to receive liver grafting?

OBJECTIVE: Patients with acute hepatic failure (AHF) were always given first priority on the transplant waiting list. We investigated whether AHF patients will deprive other patients on the waiting list of the chance of liver transplantation (LTx). METHODS AND RESULTS: From January 1999 to March 2003, a total of 423 patients were on the transplant waiting list at the National Taiwan University Hospital. Sixty-five of the patients had AHF caused by hepatitis-B-related disease (HBV, n = 52, 80%), Wilson disease (n = 3, 4.6%), drug-induced AHF (n = 3, 4.6%), and other causes (n = 7, 10.8%).Thirty-three patients died and 16 survived by medical treatment. Two received LTx abroad and 14 underwent LTx at our hospital (7 living-related; 7 cadaver). A total of 140 patients died while waiting for a transplant during the period studied. Of them, 107 were among 358 non-AHF patients (30%), and time-to-death interval was 133 +/- 175 days (median: 62); 33 were among 65 AHF patients (51%); time to death was 19 +/- 28 days (median: 8). There were 35 cadaver donor livers available during the period; 28 of 358 non-AHF patients (7.8%), and 7 of 65 AHF patients (10.7%) received cadaveric LTx. Their waiting time totaled 342 +/- 316 and 12 +/- 9 days, respectively (P < .0001). CONCLUSION: Most AHF patients died unless they received liver grafts. Even with a higher priority assigned to them, AHF patients still have little chance to get a cadaver donor liver in Taiwan, and non-AHF patients have an even slimmer chance. Therefore, we need to encourage liver donation from living-related donors.     

Applying the neoadjuvant paradigm to ductal carcinoma in situ

Local treatment options for ductal carcinoma in situ (DCIS) are virtually identical to those for early invasive breast cancer, despite the fact that the survival from this condition is much higher. Our ability to more appropriately tailor therapy for DCIS is hampered by a lack of understanding of the natural history of DCIS, our limited ability to predict the rate of progression to invasive cancer and the response to therapy, and the absence of tools to follow patients who have not had invasive treatments. Neoadjuvant therapy, which has been proven to be both safe and effective in tailoring treatments for invasive cancer, could be ideally suited to DCIS. However, neoadjuvant therapy requires that doctors and patients delay surgical treatment that has known benefits. In order to successfully introduce this approach into clinical practice, risk assessment and decision support tools will be needed to help physicians and patients feel comfortable that they are not being exposed to unnecessary or excessive risk. In addition, we need better imaging to track extent and progression of disease. Among the possible benefits of the neoadjuvant approach, we may discover that many lesions are responsive and some even reversible, leaving us with treatments that might be tailored to biology and with important clues for breast cancer prevention in high-risk women.     

Reappraisal of Percutaneous Transhepatic Biliary Drainage Tract Recurrence After Resection of Perihilar Bile Duct Cancer

Background

The high incidence of percutaneous transhepatic biliary drainage (PTBD) tract recurrence after resection of perihilar bile duct cancer (BDC) at a reference single center has suggested the need for endoscopic biliary drainage (EBD) to prevent PTBD-related tumor recurrence. To determine the general applicability of these findings, we validated the risk of PTBD tract recurrence in patients with resected BDC in our high-volume center.

Methods

The medical records of 306 patients with perihilar BDC who underwent hepatobiliary resection with curative intent over 10?years were reviewed retrospectively.

Results

Of the 306 patients, 293 (95.8%) underwent biliary decompression, 171 (56.1%) by preoperative PTBD, 62 (20.3%) by EBD alone, and 60 (19.7%) by both. Of the 231 patients who underwent PTBD, 160 (69.3%), 62 (26.8%), and 9 (3.9%) had one, two, or three catheters, respectively (mean of 1.3 catheters per patient for a median 23?days). No patient experienced synchronous PTBD tract metastasis, whereas 4 (1.7%) experienced PTBD tract recurrence a median 13.5?months after surgery, with 3 of these patients having an intraabdominal recurrence soon afterward. Only one patient had a solitary tract recurrence without intraabdominal metastasis. These patients survived for a median 25?months, which is comparable to survival outcomes after noncurative resection. No risk factor was significantly associated with PTBD tract recurrence.

Conclusions

We think that the risk of PTBD tract recurrence after resection of perihilar BDC is not negligible but is much lower than previously reported. There is no definitive reason to avoid PTBD when it is indicated.     

Improvement of Nonalcoholic Fatty Liver Disease After Bariatric Surgery in Morbidly Obese Chinese Patients

Background

Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), which appears to improve after weight loss induced by bariatric surgery in Western countries. The present study aims to determine the alterations of clinical measurements and liver histology of NAFLD after bariatric surgery in morbidly obese Chinese patients.

Methods

Between November 2006 and December 2007, 21 morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy 1?year after laparoscopic Roux-en-Y gastric bypass were enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically evaluated.

Results

The mean body mass index fell from 43.8?±?7.5 to 28.3?±?4.6?kg/m² (P?P?P?<?0.01), but not aspartate aminotransferase (P?=?0.66). Histological improvement was noted in NAS (P?P?P?P?=?0.02). Pre-operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS ?R5, 3 or 4, and ?Q2, respectively. All patients had NAS ?Q2 after surgery. Fibrosis stage also showed significant improvement (P?Conclusions Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically and histologically in morbidly obese Chinese patients.     

Purine anti-metabolite attenuates nuclear factor κB and related pro-inflammatory cytokines in experimental vasospasm

Background

Increased nuclear factor κB (NF-κB) bioexpression, as well as TNF-α, IL-1β and IL-6 levels, were observed after aneurysmal subarachnoid hemorrhage (SAH). It is of interest to investigate the effect of 6-mercaptopurine (6-mp) on cytokines/NF-κB in this SAH model.

Materials and methods

A rodent double-hemorrhage SAH model was employed. Serum and cerebrospinal fluid (CSF) samples were collected to examine IL-1, IL-6 and TNF-α levels. NF-κB subunit p65 and its inhibitor of nuclear factor κB (IκB) were examined (by Western blot). TNF-α was used to induce the phosphorylation of IκB in the presence or absence of 6-mp.

Results

Nuclear NF-κB subunit p65/IκB kinase in the basilar artery was over-expressed, and cytokines was notably increased in the SAH groups, compared with the controls (P?P?Conclusions Through inhibiting IκB bioexpression, 6-mp decreases NF-κB-related IL-1β, IL-6, and TNF-α in the presence of SAH. The study suggests 6-mp exerts vascular anti-inflammatory properties through inhibiting IκB kinase and subsequently blocks bio-activation of NF-κB and related cytokines, which may contribute to its antivasospastic effect in animals subjected to SAH.