PubMed Health⌕ Search

Biomedical subjects

Timothy D Sielaff

Publications and source records attributed to Timothy D Sielaff.

15 recordsLinked to original sources
PubMed2006

Biliary cystadenomas: hormone receptor expression and clinical management.

Biliary cystadenomas with mesenchymal stroma are neoplasms whose growth may be hormone sensitive. This study profiled the immunohistochemistry of these lesions to clarify the pathophysiology and define clinical management. Twelve patients with biliary cystadenomas were identified. Tissue was tested with a panel of probes including estrogen and progesterone receptors and compared to pancreatic and ovarian cystadenomas. Epithelial ER, PR, CD117, or SMA expression was negative in all three tumors. Epithelial CD10 expression was seen in 60% biliary, 75% pancreatic, and 0% ovarian tumors. Biliary cystadenoma stromal expression was ER+ (70%), PR+ (60%), CD10+ (40%), and c-kit+ (0%). Symptoms were seen in 92% patients. Percutaneous sclerotherapy and incomplete resection were associated with recurrence. Enucleation was the least morbid surgical technique. A role for hormonally mediated growth of biliary cystadenomas occurring through the stroma, rather than the epithelium, is suggested. Management remains complete surgical resection.

Adult↗
PubMed2005

Hypothermic maintenance of hepatocyte spheroids.

Primary hepatocytes form spheroids under some culture conditions. These spheroids exhibit many tissue-like ultrastructures and retain many liver-specific functions over a long period of time. They are attractive for many applications employing liver cells. The ability to maintain their viability and functions at a reduced temperature to allow for transportation to the site of their application will facilitate their use. Furthermore, with their structural and functional similarity, they could possibly be used as a model system for studying various liver ischemias. The effect of hypothermic treatment was assessed by oxygen consumption rate, ATP, H2O2, and caspase 8 content, as well as albumin and urea synthesis, during and posttreatment. No single outcome variable gives a superlative quantification of hypothermic damage. Taken together, the hypothermic treatment can be seen as increasingly damaging as the temperature decreases from 21 degrees C to 15 degrees C and 4 degrees C. The addition of the chemical protectants glutathione, N-acetyl-L-cystein (NAC), and tauroursodeoxycholic acid (TUDCA) decreased the damaging effect of hypothermic treatment. This protection effect was even more profound when spheroids were preincubated with the protectant for 24 h, and was most prominent at 4 degrees C. The viability of the hypothermically treated hepatocyte spheroids was confirmed by laser scanning confocal microscopy. The method reported provides a means of maintaining spheroids' viability and may allow for their distribution to application sites at a distance.

Animals↗
PubMed2004

Liver regeneration after adult living donor and deceased donor split-liver transplants.

As the number of living donor (LD) and deceased donor (DD) split-liver transplants (SLTs) have increased over the last 5 years, so too has the interest in liver regeneration after such partial-liver transplants. We looked at liver regeneration, as measured by computed tomography (CT) volumetrics, to see if there were significant differences among LDs, right-lobe LD recipients, and SLT recipients. We measured liver volume at 3 months postoperatively by using CT, and we compared the result to the patient's ideal liver volume (ILV), which was calculated using a standard equation. The study group consisted of 70 adult patients who either had donated their right lobe for LD transplants (n = 24) or had undergone a partial-liver transplant (right-lobe LD transplants, n = 24; right-lobe SLTs, n = 11; left-lobe SLTs, n = 11). DD (vs. LDs) were younger (P < 0.01), were heavier (P = 0.06), and had longer ischemic times (P < 0.01). At 3 months postoperatively, LDs had attained 78.6% of their ILV, less than the percentage for right-lobe LD recipients (103.9%; P = 0.0002), right-lobe SLT recipients (113.6%; P = 0.01), and left-lobe SLT recipients (119.7%; P = 0.0006). When liver size at the third postoperative month was compared with the liver size immediately postoperatively, LDs had a 1.85-fold increase. This was smaller than the increase seen in right-lobe LD recipients (2.08-fold), right-lobe SLT recipients (2.17-fold), and left-lobe SLT recipients (2.52-fold). In conclusion, liver regeneration, as measured by CT volume, seems to be greatest in SLT recipients. LD recipients seem to have greater liver growth than their donors. The reason for this remains unclear.

Adult↗
PubMed2003

Radiofrequency ablation causes 'thermal fixation' of hepatocellular carcinoma: a post-liver transplant histopathologic study.

Radiofrequency ablation (RFA) is increasingly used to treat hepatocellular carcinoma (HCC) in patients awaiting a liver transplant. Despite its increasing use, detailed histologic information is scarce regarding the nature of RFA-treated lesions. We identified four chronic hepatitis C patients who had RFA of their HCC before their liver transplant. For these four patients, we conducted a detailed histopathologic analysis of the treated lesions in their explanted livers. The five lesions included immediate (4 d) and long-term (14 months) post-RFA specimens. Of the five lesions, four were completely ablated. The one incompletely ablated lesion was also treated with chemoembolization. In the acute post-RFA period, a zone of interstitial hemorrhage occurred at the outer boundary of the lesion. Differing from classic tissue necrosis, the treated lesions all showed 'thermal fixation', with preserved tissue architecture and microscopic cellular detail. The cellular staining characteristics faded with time, but the treated tissue became brittle, resisted tissue breakdown, and generated a minimal wound healing response. At the periphery of the lesion, the fibrous septae of the cirrhotic liver and vascular structures appeared to demarcate or limit progression of the ablation front. A narrow hypocellular fibrous boundary with a focal 'foreign body' giant cell-type reaction developed around the edge of the ablation zone. Thus, RFA can produce immediate and complete thermal fixation of select lesions with an appropriate liver margin and can provide a satisfactory treatment option for select HCC patients before a liver transplant.

Carcinoma, Hepatocellular↗
PubMed2003

A modern approach to malignant hilar biliary obstruction.

Management of patients with malignant hilar biliary obstruction is challenging for all specialists involved in their care. Evaluation should focus on potential surgical resection, which offers the principal chance of cure; liver transplantation is offered as an experimental treatment at a few centers. Attempt at curative surgical resection is appropriate for selected tumors and often requires partial hepatectomy. Diagnosis and staging is now facilitated by the use of magnetic resonance cholangiopancreatography (MRCP), spiral computed tomography, and endoscopic ultrasonography, which should largely supplant invasive cholangiography. Use of endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography should be limited primarily to palliation of jaundice in patients with unresectable tumors and to establish tissue diagnoses in ambiguous cases. Palliation of jaundice is optimal with self-expanding metallic stents. Safe and effective drainage can be achieved by using MRCP for targeted endoscopic placement of unilateral metal stents in most cases, with bilateral stents rarely required unless undrained ducts are contaminated. Other palliative modalities for bile duct tumors include surgical bypass, intraluminal and external beam radiation therapy, chemotherapy, and photodynamic therapy.

Bile Duct Neoplasms↗
PubMed2002

Cyclooxygenase-2 inhibition augments the hepatic antitumor effect of oral Salmonella typhimurium in a model of mouse metastatic colon cancer.

INTRODUCTION: Oral inoculation with a nontoxic, attenuated strain of Salmonella typhimurium reduces tumor burden and improves survival in a mouse model of metastatic colon cancer. These effects are likely mediated by S. typhimurium-induced increases in hepatic natural killer leukocytes. Cyclooxygenase-2 inhibitors may mediate antitumor effects through antiangiogenic, immune, or proapoptotic pathways. We hypothesized that cyclooxygenase-2 inhibitors would act synergistically with S. typhimurium, resulting in additional antitumor effects. METHODS: Four groups of mice were studied: control, S. typhimurium alone, cyclooxygenase-2 inhibitor alone, and S. typhimurium plus cyclooxygenase-2 inhibitor. Mice were given normal drinking water (control, S. typhimurium alone) or water with 1,600 parts per million cyclooxygenase-2 inhibitor (cyclooxygenase-2 inhibitor alone, and S. typhimurium plus cyclooxygenase-2 inhibitor) and orally inoculated with saline (control, cyclooxygenase-2 inhibitor alone) or 10(9) S. typhimurium (S. typhimurium alone, S. typhimurium plus cyclooxygenase-2 inhibitor). Twenty-four hours later, all mice underwent laparotomy, and 5 x 10(4) MCA38 murine adenocarcinoma cells were injected into the spleen. On Day 14, hepatic tumor number and tumor volume was quantitated and hepatic leukocytes were analyzed by flow cytometry. RESULTS: Compared with control mice orally inoculated with saline, S. typhimurium-treated mice had fewer and smaller tumors; mice treated with cyclooxygenase-2 inhibitor alone had tumor burden similar to control mice, and mice treated with S. typhimurium plus cyclooxygenase-2 inhibitor had fewer and smaller tumors compared with all other groups. Increased liver natural killer cells and decreased CD4+ and CD8+ T cells were observed in both S. typhimurium-treated groups. No alterations in hepatic leukocyte phenotype were observed in mice receiving cyclooxygenase-2 inhibitor alone. CONCLUSION: Oral cyclooxygenase-2 inhibitor appeared to act synergistically with S. typhimurium to reduce tumor burden. This combination therapy may have clinical application in the treatment or prevention of hepatic metastases associated with colorectal cancer.

Adenocarcinoma↗
PubMed2002

Living related liver transplantation for recurrent hepatocellular carcinoma in a normal liver.

The role of liver transplantation for hepatocellular carcinoma (HCC) is evolving. In patients with advanced liver disease and early stage HCC, transplantation offers the best hope for cure. A living donor offers the optimal approach to a timely transplant, before disease progression obviates the potential benefit. But extending the indications beyond those designated by the United Network for Organ Sharing (UNOS) for liver transplantation for HCC is controversial [Hepatology 2001: 33: 1073; Liver Transplant 2000: 6: S1]. Cadaver split techniques and use of living donors are potentially compelling ways to test the limitations of liver transplantation for HCC, without notably reducing the cadaver organ pool. Herein, we report a rare case of a patient who developed a well-differentiated HCC in a normal liver. After resection of the index lesion and, later, of a remote recurrent lesion, a living donor liver transplant was offered. The natural history of this lesion and the management of transplantation in this setting are discussed.

Adult↗
PubMedDate not supplied

Staged laparoscopic infusion of hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPC) is a promising treatment for patients with peritoneal malignancies. Traditionally, HIPC is performed concurrently with cytoreductive surgery. However, this strategy is associated with significant morbidity and mortality. In this report, we describe our initial experience with staged laparoscopic infusion of HIPC. Five patients underwent complete open cytoreductive surgery followed by staged laparoscopic HIPC several weeks later. Primary malignancies included adenocarcinoma of the ileum (one patient), adenocarcinoma of the appendix (three patients), and adenocarcinoma of the gallbladder (one patient). At a subsequent operation, we performed laparoscopic HIPC. Quality of life was measured with the Functional Assessment of Cancer Therapy-Colon Subscale (FACT-C). Mean inflow and outflow cannula temperatures were 42.1 degrees C and 40.5 degrees C, respectively. Mean peritoneal perfusion flow rates were 689.8 ml/minute. The hospital stay for all patients was 1 to 2 days. One patient developed postoperative cellulitis, one patient died of progressive tumor, and four patients are alive without tumor progression. Quality-of-life measurements had returned to baseline 4 months after treatment. Staged laparoscopic HIPC after open cytoreductive surgery is safe, feasible, and can achieve uniform temperatures and perfusion flow rates. Although the results of this pilot study are encouraging, additional studies are required to determine long-term survival and quality of life.

Adenocarcinoma↗
PubMedDate not supplied

Local, intrahepatic, and systemic recurrence patterns after radiofrequency ablation of hepatic malignancies.

The objective of this study was to describe the recurrence patterns in patients with unresectable hepatic malignancies treated with radiofrequency ablation (RFA). As RFA is applied more widely to patients with hepatic tumors, a better understanding of the biologic behavior of these tumors and the risk of recurrence, both in the liver and systemically, is needed. A multidisciplinary team evaluated patients referred for RFA and followed them prospectively to assess local, intrahepatic, and extrahepatic disease recurrence and complication rates. Forty-five patients with 143 lesions and a minimum follow-up of 6 months (median 19.5 months) were treated. Overall, 7.7% of treated lesions had local recurrence. New intrahepatic disease was seen in 49% of patients, and 24% had evidence of new systemic tumor progression. Patients with colorectal metastatic lesions > or =4 cm at the time of the first RFA were more likely to present with local recurrence (P = 0.048). Complications occurred in 27% of patients. Although RFA has a satisfactory local failure rate and safety profile, the patient population being treated is at high risk of developing new disease. Multimodality adjuvant therapy will be necessary to realize the full potential of hepatic malignancy control with RFA.

Adult↗
PubMedDate not supplied

Laparoscopic stapled left lateral segment liver resection--technique and results.

Because of the favorable anatomy of the left lateral segment of the liver, a totally laparoscopic approach to resection is feasible. Herein we describe a technique for laparoscopic stapled resection of the left lateral segment of the liver, including the necessary anatomic criteria for a safe operation and data on clinical outcome. Five patients at our center underwent laparoscopic exploration, ultrasound examination, and resection of segments II and III. After complete mobilization of the left lateral segment and minimal portal dissection, the totally laparoscopic resections were performed with two endoscopic staple loads (4.5 mm x 60 mm) applied sequentially across the portal pedicle and the left hepatic vein. The mean operative time was 182 minutes (range 130 to 240 minutes), blood loss was 41 ml (range 25 to 50 ml), and length of hospital stay was 2.2 days (range 1 to 3 days). All three patients with malignancy had negative surgical margins. All five patients returned to normal activity or work by 1 week postoperatively. There were no complications. Patients with isolated malignant and benign diseases of the left lateral segment of the liver are candidates for totally laparoscopic resection, if evaluation demonstrates a normal liver character and hepatic parenchymal thickness less than 3 cm overlying the ligamentum venosum groove. Such patients benefit from the minimally invasive approach, with no compromise in the surgical result as compared to the open approach.

Adult↗
PubMedDate not supplied

Sustaining a bioartificial liver under hypothermic conditions.

Bioartificial liver (BAL) devices employing xenogeneic hepatocytes are being developed as a temporary support of liver failure. For clinical applications, transporting such a device from the manufacturing site to the hospital is necessary. We investigated the effect of hypothermic treatment on the performance of the collagen-entrapment BAL device developed at the University of Minnesota. A number of chemical protectants were examined for their effectiveness in minimizing damage to hepatocytes. Preincubation with protectant (tauroursodeoxycholic acid, TUDCA) before hypothermic treatment improved posttreatment BAL performance. Oxygen consumption and albumin and urea synthesis all resumed at levels comparable to pretreatment levels. The method described will facilitate the application of BAL in the treatment of liver failure.

Animals↗
PubMedDate not supplied

Management of an occluded Wallstent for a benign biliary stricture: a case report.

Laparoscopic cholecystectomy is associated with a 0.5% incidence of major common bile duct injury. Management of this uncommon complication is determined by when the injury is recognized, by its extent, and by local surgical, radiological and endoscopic expertise. The use of titanium Wallstents for benign biliary stricture has been previously described, but complications from this approach are not well documented. The management of complications from titanium Wallstent deployment for treatment of a common bile duct stricture is described.

Bile Ducts, Intrahepatic↗