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1.
Colorectal Dis ; 14(1): 48-55, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21689262

ABSTRACT

AIM: The prognostic effects of chemotherapy and various lymph node measures [positive nodes, total node count and the positive lymph node ratio (PLNR)] have been established. It is unknown whether the cancer-specific survival benefit of chemotherapy differs across these nodal prognostic categories. METHOD: This retrospective analysis of linked Surveillance, Epidemiology and End Results (SEER) data and Medicare data (SEER-Medicare)included patients ≥ 65 years of age with a diagnosis of stage III colon cancer between 1997 and 2002. We grouped patients according to the number of positive nodes (N1 and N2), total node count (≥ 12 and < 12 total nodes) and PLNR (below the 75th percentile and at least at the 75th percentile of the PLNR). The end point was colon cancer-specific mortality. RESULTS: Fifty-one per cent (3701) of the 7263 patients received adjuvant therapy during the time period 1997-2002. The mean (standard deviation) number of total nodes examined was 13 (9) and the number of positive nodes identified was 3 (3). Patients with N2 disease, < 12 total nodes examined and a high PLNR had a worse survival at 2, 3 and 5 years following colectomy. Utilization of chemotherapy demonstrated a colon cancer-specific survival benefit (hazard ratio at median follow up = 0.7; P < 0.001) that was consistent and statistically significant across the three nodal prognostic categories examined. CONCLUSION: The benefit of chemotherapy did not vary based on N stage, total node count or PLNR. The results favour a broad-based approach towards increasing the chemotherapy treatment rates in stage III patients of ≥ 65 years of age, rather than an approach that targets clinical subgroups.


Subject(s)
Chemotherapy, Adjuvant , Colonic Neoplasms/drug therapy , Colonic Neoplasms/mortality , Aged , Aged, 80 and over , Colonic Neoplasms/pathology , Female , Humans , Lymphatic Metastasis , Male , Medicare , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , SEER Program , Survival Analysis , United States/epidemiology
2.
Article in English | MEDLINE | ID: mdl-16686000

ABSTRACT

The minimally invasive treatment of liver tumors represents an alternative to the open surgery approach. Radio-frequency ablation destroys a tumor by delivering radio-frequency energy through a needle probe. Traditionally, the probe is placed manually using imaging feedback. New approaches use robotic devices to accurately place the instrument at the target. The authors developed an image-guided robotic system for percutaneous interventions using computed tomography. The paper presents a randomized patient study comparing the manual versus robotic needle placement for radio-frequency ablation procedures of liver tumors. The results of this study show that in our case robotic interventions were a very viable solution. Several treatment parameters such as radiation exposures and procedure-times were found to be significantly improved in the robotic case.


Subject(s)
Catheter Ablation/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/surgery , Pattern Recognition, Automated/methods , Radiographic Image Interpretation, Computer-Assisted/methods , Robotics/methods , Surgery, Computer-Assisted/methods , Algorithms , Artificial Intelligence , Cluster Analysis , Humans , Image Enhancement/methods , Imaging, Three-Dimensional/methods , Punctures/methods , Reproducibility of Results , Sensitivity and Specificity , Tomography, X-Ray Computed/methods , Treatment Outcome
3.
J Viral Hepat ; 11(4): 297-301, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15230851

ABSTRACT

Occult hepatitis B is defined by the presence of hepatitis B viral (HBV) DNA in the serum or liver in persons lacking hepatitis B surface antigen (HBsAg) in the serum. A high prevalence of occult HBV has been reported in hepatocellular carcinoma (HCC) from Asia, but little information is available on the prevalence of occult HBV in HCC from regions with a low prevalence of typical chronic hepatitis B infection. In a retrospective study, 19 cases of primary liver cancer were investigated for the presence of occult HBV DNA by amplification of the surface, core, and X gene. In addition, HBV copy numbers were quantitated by real time polymerase chain reaction, genotyped, and samples tested for covalently closed circular HBV DNA, which is a marker of active viral replication. Occult HBV was found in three of 19 cases (16%). Genotyping was successful in two cases, both of which were genotype A. HBV DNA copy numbers were low, all less than 10 copies/microg liver DNA. No closed circular HBV DNA was detected. Thus, in this study occult HBV was of genotype A and was found in a low percentage of cases of HCC and was associated with low tissue HBV DNA copy numbers and no detectable evidence for viral replication.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/epidemiology , Hepatitis B, Chronic/virology , Liver Neoplasms/virology , Adult , Aged , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/epidemiology , DNA, Superhelical/analysis , DNA, Viral/analysis , Female , Genotype , Hepatitis B Surface Antigens/blood , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Hepatitis B, Chronic/complications , Humans , Liver/virology , Liver Neoplasms/complications , Male , Middle Aged , Polymerase Chain Reaction , Prevalence , Retrospective Studies , Virus Replication
4.
Science ; 294(5545): 1343-6, 2001 Nov 09.
Article in English | MEDLINE | ID: mdl-11598267

ABSTRACT

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.


Subject(s)
Colorectal Neoplasms/enzymology , Colorectal Neoplasms/genetics , Immediate-Early Proteins/genetics , Neoplasm Metastasis/genetics , Protein Tyrosine Phosphatases/genetics , Adenoma/enzymology , Adenoma/genetics , Adenoma/pathology , Chromosome Mapping , Chromosomes, Human, Pair 8 , Colon/enzymology , Colorectal Neoplasms/pathology , Gene Amplification , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Library , Humans , Immediate-Early Proteins/metabolism , Intestinal Mucosa/enzymology , Neoplasm Proteins , Neoplasm Staging , Polymerase Chain Reaction , Protein Tyrosine Phosphatases/metabolism , Rectum/enzymology
5.
Pharm Res ; 18(7): 899-906, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11496947

ABSTRACT

PURPOSE: The purpose of our study was to develop an injectable polymeric system for the long-term localized delivery of bioactive interleukin-2 for antitumor immunotherapy. METHODS: IL-2 was encapsulated into gelatin and chondroitin-6-sulfate using an aqueous-based complex coacervation. CTLL-2 cells were used to measure the bioactivity of released IL-2 and radiolabeled IL-2 was used for release studies in the rat brain and mouse liver. Antitumor efficacy studies were carried out in primary (9L gliosarcoma) and metastatic (B16-F10 melanoma) brain tumor models in rats and mice, respectively, as well as a murine liver tumor model (CT26 carcinoma). Survivors of the metastatic brain tumor challenge were rechallenged with tumor in the opposite lobe of the brain to confirm that antitumor immunologic memory had developed. RESULTS: Bioactive IL-2 was released for over 2 weeks in vitro and in vivo IL-2 release showed significant IL-2 levels for up to 21 days. Polymeric IL-2 microspheres injected intratumorally were statistically more effective in protecting animals challenged with fatal tumor doses in the brain and the liver than placebo or autologous tumor cells genetically engineered to secrete IL-2. Immunologic memory was induced following IL-2 microsphere therapy in the B16-F10 brain tumor model that was capable of protecting 42% of animals from a subsequent intracranial tumor challenge, suggesting that tumor destruction was mediated by the immune system. CONCLUSIONS: Local IL-2 therapy using novel polymeric carriers. aimed at stimulating long-lasting antitumor immunity, may provide an improved method of treating a variety of cancers.


Subject(s)
Antineoplastic Agents/administration & dosage , Biocompatible Materials/administration & dosage , Brain Neoplasms/drug therapy , Drug Delivery Systems/methods , Interleukin-2/administration & dosage , Liver Neoplasms, Experimental/drug therapy , Animals , Biocompatible Materials/metabolism , Brain/drug effects , Brain/pathology , Brain Neoplasms/pathology , Brain Neoplasms/prevention & control , Liver Neoplasms, Experimental/prevention & control , Melanoma, Experimental , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microspheres , Polymers/administration & dosage , Polymers/metabolism , Rats , Rats, Inbred F344 , Tumor Cells, Cultured
6.
Trends Mol Med ; 7(7): 307-13, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11425639

ABSTRACT

Despite recent advances in the treatment of colorectal cancer, the overall survival rate for those patients with advanced locoregional disease remains less than 50%. Although adjuvant systemic chemotherapy has improved survival of these patients, more effective therapies are needed. Immunotherapy is an approach that could have a particular role in the adjuvant therapy of colorectal cancer. There is now convincing evidence that the immune system can specifically recognize and destroy malignant cells. Although both antibody- and T-cell-mediated anti-tumor responses have been documented, the cellular immune response with its direct cytotoxic mechanisms is felt to be the principal anti-tumor arm of the immune system. Analysis of the T cells that recognize tumors has led to the identification and characterization of many tumor-associated antigens including several colorectal antigens. Current approaches to developing a vaccine for colorectal cancer use our expanded understanding of these tumor-associated antigens and the conditions that allow development of an effective cellular immune response to them.


Subject(s)
Antigens, Neoplasm/immunology , Cancer Vaccines , Colorectal Neoplasms/immunology , Colorectal Neoplasms/therapy , BCG Vaccine , Dendritic Cells/immunology , Humans , Immunotherapy/methods , Vaccines, Synthetic
7.
J Comput Assist Tomogr ; 25(1): 74-80, 2001.
Article in English | MEDLINE | ID: mdl-11176297

ABSTRACT

PURPOSE: The purpose of this work was to define the temporal CT characteristics of hepatic and renal ablation following point-source radioablation utilizing a low energy, photon X-ray source emitted from a miniature probe. METHOD: Twelve mongrel dogs underwent each of three hepatic and two renal point-source radiation ablations. Animals underwent serial, dual phase, spiral CT scans and were killed at 1, 3, and 6 months after treatment. RESULTS: Ablative lesions were clearly visible at 1 month following therapy and consistently diminished in size over the 6 months of follow-up. Lesion size tended to be proportional to dose delivered. Both hepatic and renal lesions were low in attenuation with frequent rim enhancement that diminished over time. Hepatic lesions frequently showed transient hepatic attenuation differences (THADs). Lesion size appeared independent of proximity to vessels. CONCLUSION: Following hepatic or renal interstitial radiotherapy, lesions are generated that are similar in CT appearance to those produced by other ablative techniques. The presence of rim or THAD enhancement can be seen early on as part of the normal tissue-healing response.


Subject(s)
Kidney Neoplasms/radiotherapy , Liver Neoplasms/radiotherapy , Tomography, X-Ray Computed , Animals , Disease Models, Animal , Dogs , Female , Kidney Neoplasms/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Time Factors , Tomography, X-Ray Computed/methods , Urography
8.
Nat Biotechnol ; 19(1): 78-81, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11135558

ABSTRACT

The analysis of loss of heterozygosity (LOH) is perhaps the most widely used technique in cancer genetics. In primary tumors, however, the analysis of LOH is fraught with technical problems that have limited its reproducibility and interpretation. In particular, tumors are mixtures of neoplastic and nonneoplastic cells, and the DNA from the nonneoplastic cells can mask LOH. We here describe a new experimental approach, involving two components, to overcome these problems. First, a form of digital PCR was employed to directly count, one by one, the number of each of the two alleles in tumor samples. Second, Bayesian-type likelihood methods were used to measure the strength of the evidence for the allele distribution being different from normal. This approach imparts a rigorous statistical basis to LOH analyses, and should be able to provide more reliable information than heretofore possible in LOH studies of diverse tumor types.


Subject(s)
Chromosomes, Human, Pair 18 , Colorectal Neoplasms/genetics , DNA, Neoplasm/genetics , Loss of Heterozygosity , Neoplasm Invasiveness/genetics , Polymorphism, Single Nucleotide , Alleles , Bayes Theorem , Colorectal Neoplasms/pathology , Humans , Likelihood Functions , Neoplasm Staging , Polymerase Chain Reaction/methods
9.
J Gastrointest Surg ; 5(4): 383-7, 2001.
Article in English | MEDLINE | ID: mdl-11985979

ABSTRACT

Combined chemotherapy and radiation therapy is the standard treatment for epidermoid carcinoma of the anal canal. Failures are often not associated with distant recurrence and are therefore potentially amenable to salvage abdominoperineal resection. The aim of this study was to review our experience with abdominoperineal resection following failure of chemoradiation therapy for epidermoid carcinoma of the anus. Between 1980 and 1998, 17 patients underwent salvage abdominoperineal resection following failure of chemoradiation therapy. Four patients were excluded from survival analysis because resection was performed with palliative intent. Survival curves were based on the method of Kaplan and Meier, and univariate analysis of predictive variables was performed using the log-rank test. Twelve patients underwent abdominoperineal resection for persistent disease and five patients for recurrent disease. No operative deaths occurred, but local complications including perineal wound infection and wound breakdown was seen in 8 of 17 patients and 6 of 17 patients, respectively. Patients undergoing omental flap reconstruction (n = 3) or no pelvic reconstruction (n = 5) had a higher incidence of perineal breakdown compared to those undergoing muscle flap reconstruction (n = 9) (P <0.05). The median follow-up time for the patients operated on with curative intent was 53 months. The 5-year actuarial survival was 47%. Potential prognostic factors that were not found to have an impact on survival included margin status of resection, sphincter invasion, and degree of differentiation. Only pathologic tumor size greater than 5.0 cm (P <0.001) and age over 55 years (P <0.05) adversely affected survival. Selected patients with recurrent or persistent anal carcinoma following chemoradiation therapy can be offered salvage abdominoperineal resection. This operation is associated with a high incidence of local wound complications, and muscle flap reconstruction should be considered when possible. Prolonged survival can be achieved in some patients following salvage resection for epidermoid carcinoma of the anal canal.


Subject(s)
Anus Neoplasms/surgery , Carcinoma, Squamous Cell/surgery , Neoplasm Recurrence, Local/surgery , Anus Neoplasms/mortality , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/therapy , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Postoperative Complications/epidemiology , Plastic Surgery Procedures , Salvage Therapy , Surgical Flaps , Survival Analysis , Time Factors , Treatment Failure , Treatment Outcome
10.
AJR Am J Roentgenol ; 175(6): 1653-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11090399

ABSTRACT

OBJECTIVE: The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T with and without ferumoxides with dual-phase helical CT for the detection of hepatic lesions in candidates for hepatic surgery. SUBJECTS AND METHODS: Patients with known or suspected hepatic lesions who were eligible for surgery underwent dual-phase helical CT at 20 and 70 sec after the start of contrast material injection and phased array MR imaging using fast spin-echo T2-weighted imaging and gradient-echo T1-weighted imaging before and after ferumoxides infusion of 0.56 mg of iron per kilogram of body weight. Three observers who were unaware of the surgical findings separately reviewed the CT scans and unenhanced and enhanced MR images of 24 patients who completed the protocol. The observers' findings were compared with results obtained at surgery using intraoperative sonography and having histopathologic confirmation. Statistical analysis was performed using a segment-by-segment analysis. RESULTS: Eighty-two lesions were found at surgery. The sensitivity of CT, unenhanced MR imaging, and enhanced MR imaging for blinded observers was 60.4%, 62.0%, and 68.2%, respectively. The specificity was 89.2%, 81.9%, and 81.6%, respectively. Five lesions in three patients were not detected preoperatively using any of the techniques. MR imaging found additional lesions not detected on CT in four patients; CT detected one additional lesion not seen on MR imaging. CONCLUSION: Ferumoxides-enhanced MR imaging of the liver shows a trend toward increased sensitivity compared with dual-phase helical CT. Specificity of helical CT was superior to that of enhanced MR imaging for most observers.


Subject(s)
Iron , Liver Diseases/diagnosis , Magnetic Resonance Imaging/methods , Oxides , Tomography, X-Ray Computed/methods , Case-Control Studies , Contrast Media , Dextrans , Female , Ferrosoferric Oxide , Humans , Liver Diseases/surgery , Liver Neoplasms/diagnosis , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Magnetite Nanoparticles , Male , Middle Aged , Sensitivity and Specificity , Suspensions
11.
Radiology ; 217(2): 477-86, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11058649

ABSTRACT

PURPOSE: To use radiologic-histopathologic correlation in an animal model to distinguish normal postoperative findings from evidence of residual tumor after cryoablation of malignant hepatic tumors. MATERIALS AND METHODS: Hepatic cryoablation was performed in 12 rabbits with VX2 tumors and in two healthy rabbits. Nonenhanced and dynamic contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging and power and color Doppler flow ultrasonography (US) were performed 7-8 days after cryoablation. Histopathologic findings were correlated with imaging findings. RESULTS: Twenty tumors of 5-20 mm (mean, 10 mm) and seven areas of normal liver were treated with cryolesions of 11-21 mm (mean, 15 mm). All cryolesions exhibited arterial phase rim enhancement at CT and MR imaging, and 13 (57%) of 23 lesions demonstrated peripheral flow at US because of granulation tissue. There was macroscopic recurrence in 15 (75%) of 20 treated tumors; 14 (93%) appeared as peripheral nodularity with low-grade enhancement. Necrotic tissue did not enhance. Intact vessels extended up to 6 mm inside cryolesion margins and caused focal internal enhancement and Doppler flow. Areas of high signal intensity on T2-weighted MR images correlated with liquefaction necrosis, granulation tissue, and tumor. CONCLUSION: In this animal model, recurrent tumor typically appeared as focal nodules at the cryolesion periphery. Rim and central foci of enhancement, Doppler flow, and increased signal intensity on T2-weighted MR images can be normal findings after hepatic cryoablation.


Subject(s)
Cryosurgery , Liver Neoplasms, Experimental/surgery , Liver/surgery , Neoplasm Recurrence, Local , Animals , Liver/diagnostic imaging , Liver/pathology , Liver Neoplasms, Experimental/diagnosis , Liver Neoplasms, Experimental/diagnostic imaging , Liver Neoplasms, Experimental/pathology , Magnetic Resonance Imaging , Male , Rabbits , Tomography, X-Ray Computed , Ultrasonography, Doppler, Color
12.
Ann Surg ; 232(3): 419-29, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10973392

ABSTRACT

OBJECTIVE: To evaluate the endpoints of complications (specifically pancreatic fistula and total complications) and death in patients undergoing pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Four randomized, placebo-controlled, multicenter trials from Europe have evaluated prophylactic octreotide (the long-acting synthetic analog of native somatostatin) in patients undergoing pancreatic resection. Each trial reported significant decreases in overall complication rates, and two of the four reported significantly lowered rates of pancreatic fistula in patients receiving prophylactic octreotide. However, none of these four trials studied only pancreaticoduodenal resections, and all trials had high pancreatic fistula rates (>19%) in the placebo group. A fifth randomized trial from the United States evaluated the use of prophylactic octreotide in patients undergoing pancreaticoduodenectomy and found no benefit to the use of octreotide. Prophylactic use of octreotide adds more than $75 to the daily hospital charge in the United States. In calendar year 1996, 288 patients received octreotide on the surgical service at the authors' institution, for total billed charges of $74,652. METHODS: Between February 1998 and February 2000, 383 patients were recruited into this study on the basis of preoperative anticipation of pancreaticoduodenal resection. Patients who gave consent were randomized to saline control versus octreotide 250 microg subcutaneously every 8 hours for 7 days, to start 1 to 2 hours before surgery. The primary postoperative endpoints were pancreatic fistula, total complications, death, and length of hospital stay. RESULTS: Two hundred eleven patients underwent pancreaticoduodenectomy with pancreatic-enteric anastomosis, received appropriate saline/octreotide doses, and were available for endpoint analysis. The two groups were comparable with respect to demographics (54% male, median age 66 years), type of pancreaticoduodenal resection (60% pylorus-preserving), type of pancreatic-enteric anastomosis (87% end-to-side pancreaticojejunostomy), and pathologic diagnosis. The pancreatic fistula rates were 9% in the control group and 11% in the octreotide group. The overall complication rates were 34% in the control group and 40% in the octreotide group; the in-hospital death rates were 0% versus 1%, respectively. The median postoperative length of hospital stay was 9 days in both groups. CONCLUSIONS: These data demonstrate that the prophylactic use of perioperative octreotide does not reduce the incidence of pancreatic fistula or total complications after pancreaticoduodenectomy. Prophylactic octreotide use in this setting should be eliminated, at a considerable cost savings.


Subject(s)
Octreotide/administration & dosage , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy , Postoperative Complications/prevention & control , Aged , Double-Blind Method , Female , Humans , Male , Middle Aged , Octreotide/adverse effects , Pancreatic Fistula/etiology , Pancreatic Fistula/mortality , Postoperative Complications/etiology , Postoperative Complications/mortality , Prospective Studies , Survival Rate , Treatment Outcome
13.
Oncology (Williston Park) ; 14(7): 1085-98; discussion 1098-102, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10929592

ABSTRACT

Hepatocellular carcinoma (HCC) is responsible for a significant amount of morbidity and mortality throughout the world. In many countries, including the United States, a definite increase in the incidence of HCC has been reported recently, largely attributable to the increasing incidence of hepatitis C infection. Unfortunately, the current management of HCC is confusing due to the large number of treatment options available. The difficulty of managing a patient with HCC is compounded by the lack of well-designed, randomized clinical trials comparing the various treatment modalities. Nevertheless, many exciting management options are currently available that may prove valuable in the treatment of this disease. Partial hepatic resection or, in some instances, liver transplantation offers the best chance for cure. However, various ablative therapies, including percutaneous ethanol injection, radiofrequency ablation, and cryosurgery, may produce a survival benefit. In the future, systemic chemotherapy and transarterial chemoembolization, employed either alone or as adjuncts to ablation or resection, may play an increasing role in palliating or down-staging a patient with advanced HCC. This overview of the state-of-the-art management of HCC attempts to guide the practicing physician in selecting the best treatment plan for an individual with HCC.


Subject(s)
Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Carcinoma, Hepatocellular/diagnosis , Cryosurgery , Embolization, Therapeutic , Hepatectomy , Humans , Liver Neoplasms/diagnosis , Neoplasm Metastasis , Neoplasm Staging , Tomography, X-Ray Computed
14.
J Am Coll Surg ; 191(2): 164-74, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10945360

ABSTRACT

BACKGROUND: Intratumoral ablative therapy is being used increasingly for the treatment of primary and secondary hepatic malignancies. The interstitial point-source photon radiosurgery system (PRS) is a novel ablative technique that uses radiation therapy similar in dosimetry to interstitial brachytherapy. STUDY DESIGN: To determine the feasibility, toxicity, and local tissue destructive capabilities of the PRS in the liver, preliminary studies in a nontumor-bearing canine model were examined. A 6-month survival study was conducted. Each animal received three radiation treatments, in the right, central, and left hepatic regions. Three low-dose treatments were delivered to each of six animals (group A), generating a 2.0-cm-diameter radiated sphere with a dose of 20 Gy at the lesion edge. Three high-dose treatments were delivered to each of six animals (group B), generating a 3.0-cm-diameter radiated sphere with 20 Gy at the lesion edge. RESULTS: The treatment reproducibly generated sharply demarcated hepatic ablative lesions proportional to the administered dose. Mean lesion diameter at 1 month was 1.6+/-0.2 cm in group A and 3.4+/-1.0 cm in group B. Lesion size was independent of intrahepatic location, including near vascular structures. PRS therapy, when applied to portal structures, resulted in hilar damage. Hilar damage appeared to be associated with arteriolar thrombosis and bile duct injury. Treatment of regions adjacent to large hepatic veins and the IVC was not associated with vessel thrombosis or stricture. CONCLUSIONS: PRS ablation is a generally well-tolerated method that results in consistent, well-demarcated, symmetric lesions of complete necrosis with minimal adjacent parenchymal injury. Application of such an approach for the treatment of liver tumors is promising.


Subject(s)
Liver/surgery , Radiosurgery/methods , Animals , Arterioles/radiation effects , Bile Ducts, Intrahepatic/radiation effects , Disease Models, Animal , Dogs , Dose-Response Relationship, Radiation , Equipment Design , Feasibility Studies , Female , Hepatic Veins/radiation effects , Liver/blood supply , Liver/radiation effects , Liver Neoplasms/surgery , Photons , Radiation Injuries, Experimental/etiology , Radiosurgery/adverse effects , Radiosurgery/instrumentation , Radiotherapy Dosage , Reproducibility of Results , Survival Rate , Thrombosis/etiology , Vena Cava, Inferior/radiation effects
15.
J Hepatol ; 33(1): 91-8, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10905591

ABSTRACT

BACKGROUND/AIMS: We have previously reported a recombinant vaccinia-based vaccine (vac-Sig/E7/LAMP-1) that demonstrated a significant anti-tumor effect in a subcutaneous tumor challenge model. Since the liver is one of the most common sites for tumor metastasis and organ microenvironments may modulate tumor cell responses to therapies, the aim of the present study was to evaluate the potency of vac-Sig/E7/LAMP-1 in treating E7-expressing tumors grown in the liver. METHODS: For in vivo tumor prevention experiments, mice were vaccinated intraperitoneally with vac-Sig/E7/LAMP-1 followed by intrahepatic tumor challenge. For in vivo tumor regression experiments, mice were first challenged with tumor cells and then vaccinated with vac-Sig/E7/LAMP-1 intraperitoneally. In addition, enzyme-linked immunospot assays were used to determine the frequency of E7-specific T cell precursors. RESULTS: For in vivo tumor protection experiments, tumor growth was observed in all of the mice vaccinated with wild-type vaccinia and 60% of the mice vaccinated with wild-type E7 vaccinia. All of the mice vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after tumor challenge. For the tumor regression assays, all of the mice vaccinated with vac-Sig/E7/LAMP-1 remained tumor-free 30 days after vaccination. In contrast, all of those mice receiving culture medium, wild-type vaccinia, or wild-type E7 vaccinia developed tumors in the liver. In addition, mice vaccinated with vac-Sig/E7/LAMP-1 had the highest E7-specific CD8+ T cell precursors. CONCLUSIONS: Our data suggest that vac-Sig/E7/LAMP-1 is an effective vaccine for controlling E7-expressing tumors grown in the liver and our model suggests that antigen-specific immunotherapy may represent a powerful tool for treating liver tumors with characterized tumor-specific antigens. In addition, our data indicate that the number of E7-specific CD8+ T cell precursors directly correlated with the anti-tumor effect generated by Sig/E7/LAMP-1 vaccinia.


Subject(s)
Immunotherapy , Liver Neoplasms/immunology , Liver Neoplasms/therapy , Oncogene Proteins, Viral/analysis , Oncogene Proteins, Viral/immunology , Animals , Antibody Formation , Antigens, CD/immunology , Cell Division , Epitopes , Liver Neoplasms/pathology , Liver Neoplasms/prevention & control , Lysosomal Membrane Proteins , Membrane Glycoproteins/immunology , Mice , Neoplasm Transplantation , Papillomavirus E7 Proteins , Tumor Cells, Cultured , Vaccination , Vaccines, Synthetic/therapeutic use
16.
Am J Pathol ; 156(5): 1641-51, 2000 May.
Article in English | MEDLINE | ID: mdl-10793075

ABSTRACT

Medullary carcinomas of the pancreas are a recently described, histologically distinct subset of poorly differentiated adenocarcinomas that may have a unique pathogenesis and clinical course. To further evaluate these neoplasms, we studied genetic, pathological, and clinical features of 13 newly identified medullary carcinomas of the pancreas. Nine (69%) of these had wild-type K-ras genes, and one had microsatellite instability (MSI). This MSI medullary carcinoma, along with three previously reported MSI medullary carcinomas, were examined immunohistochemically for Mlh1 and Msh2 expression, and all four expressed Msh2 but did not express Mlh1. In contrast, all of the medullary carcinomas without MSI expressed both Msh2 and Mlh1. Remarkably, the MSI medullary carcinoma of the pancreas in the present series arose in a patient with a synchronous but histologically distinct cecal carcinoma that also had MSI and did not express Mlh1. The synchronous occurrence of two MSI carcinomas suggests an inherited basis for the development of these carcinomas. Indeed, the medullary phenotype, irrespective of MSI, was highly associated with a family history of cancer in first-degree relatives (P < 0.001). Finally, one medullary carcinoma with lymphoepithelioma-like features contained Epstein-Barr virus-encoded RNA-1 by in situ hybridization. Therefore, because of medullary carcinoma's special genetic, immunohistochemical, and clinical features, recognition of the medullary variant of pancreatic adenocarcinoma is important. Only by classifying medullary carcinoma as special subset of adenocarcinoma can we hope to further elucidate its unique pathogenesis.


Subject(s)
Carcinoma, Medullary/pathology , DNA-Binding Proteins , Pancreatic Neoplasms/pathology , Adaptor Proteins, Signal Transducing , Adult , Aged , Aged, 80 and over , Carcinoma, Medullary/genetics , Carcinoma, Medullary/metabolism , Carrier Proteins , Epstein-Barr Virus Infections/virology , Family Health , Female , Genes, ras/genetics , Herpesvirus 4, Human/genetics , Humans , Immunohistochemistry , In Situ Hybridization , Male , Microsatellite Repeats/genetics , Middle Aged , Multivariate Analysis , MutL Protein Homolog 1 , MutS Homolog 2 Protein , Mutation , Neoplasm Proteins/analysis , Nuclear Proteins , Pancreas/chemistry , Pancreas/pathology , Pancreas/virology , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Phenotype , Proto-Oncogene Proteins/analysis , RNA, Viral/genetics , Survival Analysis
17.
J Endourol ; 14(2): 111-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10772501

ABSTRACT

BACKGROUND AND PURPOSE: A miniature photon radiosurgery system (PRS) has been described as an alternative to surgical resection and external-beam radiation for tumors and may now offer an alternative for ablation of renal lesions. We evaluated the feasibility of ablation by PRS in a normal parenchyma canine model. MATERIALS AND METHODS: Twelve mongrel dogs were used in this survival study. In the left and right kidneys of each animal, a peripheral lesion and central-hilar lesion, respectively, were induced with PRS. The probes were placed in the renal parenchyma, and local radiation of 15 Gy at a radius of 1.3 cm was delivered over 10 minutes. Serum electrolytes were measured serially. Computed tomography scans were obtained, and the animals were sacrificed for pathologic correlation. In a separate study, the liver received three additional treatments of 10 to 20 minutes of radiation. RESULTS: Eleven dogs survived this 6-month study and were sacrificed as scheduled. One animal expired after 2 weeks from radiation-induced fulminant hepatic failure with normal renal function. No other complications were observed. The average lesion size was 2.5 cm in diameter. Histologic analysis confirmed coagulative necrosis with sharp demarcation from the surrounding parenchyma. CONCLUSION: Preliminary studies demonstrate the feasibility of PRS ablation of the renal parenchyma. Further tumor model testing will be important to determine the ultimate efficacy of local photon radiation energy.


Subject(s)
Kidney/surgery , Photons , Radiosurgery , Animals , Dogs , Equipment Design , Feasibility Studies , Kidney/diagnostic imaging , Kidney/pathology , Liver Failure/etiology , Radiation Injuries, Experimental , Radiosurgery/adverse effects , Radiosurgery/instrumentation , Reference Values , Survival Analysis , Tomography, X-Ray Computed , Urography
18.
J Gastrointest Surg ; 4(2): 168-77, 2000.
Article in English | MEDLINE | ID: mdl-10675240

ABSTRACT

Biliary leaks and injuries are not an uncommon occurrence following laparoscopic cholecystectomy. Bile leaks associated with the biliary anatomic variant of a low-inserting right segmental hepatic duct can be particularly difficult to diagnose in that results of endoscopic retrograde cholangiography (ERC) are usually interpreted as "normal" with no leaks demonstrated. The aim of this study was to describe a single institution's experience with nine patients with biliary leaks associated with this anatomic variant and to discuss their management. A retrospective analysis of the hospital records of all patients with bile duct injuries managed at a single institution between 1980 and July 1998, inclusive, was performed. Nine patients were identified as having an isolated right segmental hepatic duct injury associated with a biliary leak. Seven (78%) of the nine patients had undergone a laparoscopic cholecystectomy, whereas the remaining two patients (22%) had undergone an open cholecystectomy. All of the patients had undergone endoscopic retrograde cholangiography at outside institutions, the results of which had been interpreted as normal with no apparent leaks. The median interval from the time of cholecystectomy to referral was 1.4 months. All patients were managed with initial percutaneous access of the involved right segmental biliary system, with placement of a percutaneous transhepatic stent. After the biliary leak was controlled, all patients underwent Roux-en-Y hepaticojejunostomy to the isolated biliary segment. All patients had an uncomplicated postoperative course. There were no postoperative anastomotic leaks. Postoperative stenting was maintained for a mean of 8 months. Six (67%) of the nine patients had a long-term successful outcome with minimal or no symptoms. In three patients, recurrent symptoms with pain and/or cholangitis developed at a mean of 34 months. All three patients underwent percutaneous cholangiography, which demonstrated an anastomotic stricture, and all were managed with percutaneous balloon dilatation with a successful outcome. Currently eight (89%) of the nine patients are asymptomatic, with a mean follow-up of 70.4 months (range 12 to 226 months). One patient had intermittent right upper quadrant pain with normal liver function tests but has not required intervention. Isolated right segmental hepatic ductal injury with biliary leakage is an uncommon complication following laparoscopic cholecystectomy. A diagnostic dilemma is created by the presence of a bile leak with a normal endoscopic retrograde cholangiogram. Management begins with percutaneous access of the transected isolated ductal system followed by reconstruction as a Roux-en-Y hepaticojejunostomy.


Subject(s)
Cholecystectomy, Laparoscopic/adverse effects , Hepatic Duct, Common/injuries , Hepatic Duct, Common/surgery , Adult , Aged , Cholangiopancreatography, Endoscopic Retrograde , Female , Hepatic Duct, Common/diagnostic imaging , Humans , Male , Medical Records , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed
19.
AJR Am J Roentgenol ; 174(2): 471-5, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10658727

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the effect of lesion enhancement on the conspicuity of small hypovascular hepatic tumors in an animal model. MATERIALS AND METHODS: Seven VX2 hepatic tumors in five rabbits were imaged. Dynamic contrast-enhanced CT was performed at a single level centered over the lesions at 5-sec intervals for 119 sec after injection of 2 ml/kg i.v. contrast material at 2 ml/sec. Attenuation was measured over time within regions of interest in the tumor and normal liver, aorta, inferior vena cava, and portal vein. Lesion conspicuity, defined as the difference between the attenuation of the uninvolved liver and neoplasm, was calculated. RESULTS: The mean diameter of the tumors on CT was 10 mm (range, 6-15 mm). The tumors appeared as low-attenuation lesions with progressive enhancement during the arterial phase and early portal phase. Peak mean lesion attenuation was 60 +/- 27 H (enhancement, 23 H) at 64 sec. Peak mean lesion conspicuity was 80 +/- 18 H at 39 sec, occurring 10 sec before the peak mean hepatic attenuation of 135 +/- 15 H (enhancement, 67 H) at 49 sec. Relative lesion conspicuity paralleled relative enhancement of the liver throughout the imaging period. CONCLUSION: Although low-level tumor enhancement during the arterial phase and early portal phase reduced the conspicuity of small hypovascular tumors in this animal model, our results support the use of maximum liver enhancement as a marker for peak lesion conspicuity.


Subject(s)
Liver Neoplasms/blood supply , Liver Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Animals , Rabbits
20.
Urology ; 55(1): 25-30, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10654889

ABSTRACT

OBJECTIVES: To present the preliminary results of renal ablative cryosurgery in selected patients. METHODS: Seven patients were treated, all of whom had small peripheral tumors and chose not to undergo partial or radical nephrectomy. Four patients underwent a rib-sparing flank incision; the remaining three underwent laparoscopy. All tumors were biopsied before cryoablation. Intraoperative ultrasound was used to monitor the cryolesion. RESULTS: There were no intraoperative complications. The estimated blood loss averaged 111 mL. To date, 6 of the 7 patients have undergone at least one follow-up computed tomography scan (14.2 months average follow-up); all these scans demonstrated partial resolution of the lesion. Clinically, the patients tolerated the procedure without any renal complications or significant changes in creatinine. CONCLUSIONS: This limited clinical trial has demonstrated the feasibility of treating small peripherally located renal tumors with cryosurgery with minimal morbidity and a favorable outcome. Further studies are necessary to determine the long-term efficacy of this treatment modality.


Subject(s)
Cryosurgery , Kidney Neoplasms/surgery , Aged , Aged, 80 and over , Female , Humans , Kidney Neoplasms/diagnosis , Male , Middle Aged
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