A simplified method to estimate Diphyllobothrium spp. infection in salmonids.

Some fish parasites constitute severe management problems as they may cause mortality of their fish host or are important zoonoses of humans. Parasite assessments are therefore critical to keep track of infections. If conventional sampling techniques can be simplified, parasite assessments might be easier to obtain, less time-consuming and more extensive. In this study, we compare the assessed number of Diphyllobothrium spp. cysts (CYST) with the counted number of Diphyllobothrium spp. plerocercoid larvae recovered using a conventional digestive technique (LARV). The aim was to determine the potential of using CYST as a simplified methodology for assessing Diphyllobothrium spp. infection in salmonids. In total, 365 brown trout and 424 Arctic charr were sampled from nine lakes in subarctic Norway. Strong correlation, significant linear relationship and large amount of explained variation were found between log10 CYST and log10 LARV in both fish species. The method had a slight, but not significant tendency to work better in charr compared to trout. In addition, absolute difference between CYST and LARV increased at parasite intensities >100 indicating that the method has reduced functionality when estimating parasite intensity in heavily infected salmonid populations. However, overall, using this simplified and less time-consuming methodology, a good indication of Diphyllobothrium spp. intensity, abundance and prevalence was obtained. We suggest that this method provides a sound proxy of the Diphyllobothrium spp. burden and have the potential to be used in parasite assessment during fish monitoring and fisheries management surveys, particularly if the time and resources for detailed parasite studies are not available.

Effects of fish species composition on Diphyllobothrium spp. infections in brown trout - is three-spined stickleback a key species?

Subarctic populations of brown trout (Salmo trutta) are often heavily infected with cestodes of the genus Diphyllobothrium, assumedly because of their piscivorous behaviour. This study explores possible associations between availability of fish prey and Diphyllobothrium spp. infections in lacustrine trout populations. Trout in (i) allopatry (group T); (ii) sympatry with Arctic charr (Salvelinus alpinus) (group TC); and (iii) sympatry with charr and three-spined stickleback (Gasterosteus aculeatus) (group TCS) were contrasted. Mean abundance and intensity of Diphyllobothrium spp. were higher in group TCS compared to groups TC and T. Prevalence, however, was similarly higher in groups TCS and TC compared to group T. Zero-altered negative binomial modelling identified the lowest probability of infection in group T and similar probabilities of infection in groups TC and TCS, whereas the highest intensity was predicted in group TCS. The most infected trout were from the group co-occurring with stickleback (TCS), possibly due to a higher availability of fish prey. In conclusion, our study demonstrates elevated Diphyllobothrium spp. infections in lacustrine trout populations where fish prey are available and suggests that highly available and easily caught stickleback prey may play a key role in the transmission of Diphyllobothrium spp. parasite larvae.

Epidermal response of rainbow trout to Ichthyobodo necator: immunohistochemical and gene expression studies indicate a Th1-/Th2-like switch.

Infections with the parasitic flagellate Ichthyobodo necator (Henneguy, 1883) cause severe skin and gill disease in rainbow trout Oncorhynchus mykiss (Walbaum, 1792) juveniles. The epidermal disturbances including hyperplasia and mucous cell exhaustion caused by parasitization are known, but no details on specific cellular and humoral reactions have been presented. By applying gene expression methods and immunohistochemical techniques, further details of immune processes in the affected skin can be presented. A population of I. necator was established in the laboratory and used to induce an experimental infection of juvenile rainbow trout. The course of infection was followed by sampling for parasite enumeration, immunohistochemistry (IHC) and quantitative PCR (qPCR) on days 0, 5, 9 and 14 post-infection. IHC showed a significant increase in the occurrence of IgM-positive cells in the skin of the infected fish, whereas IgT-positive cells were eliminated and the number of CD8-positive cells declined. qPCR studies supported the IHC findings showing a significant increase in IgM and a decrease in the CD8 gene expression. In addition, genes encoding innate immune genes such as lysozyme, SAA and cathelicidin 2 were up-regulated. Expression of cytokines (IL-1ß, IL-4/13A, IL-6, IL-8, IL-10), the cell marker CD4 and the transcription factor GATA3 showed a significant increase after infection. Cytokine profiling including up-regulation of IL-4/13A and IL-10 genes and transcription factor GATA3 connected to the proliferation of IgM producing lymphocytes suggests a partial shift towards a Th2 response associated with the I. necator infection.

Interferon enhancement of radioimmunotherapy for colon carcinoma.

Recombinant human gamma-interferon (IFN-gamma) has recently been shown to enhance localization of radiolabeled monoclonal antibodies (MAb) to human colon carcinoma xenografts in athymic mice. The present study investigates the ability of gamma-interferon to enhance radioimmunotherapy of a low carcinoembryonic antigen-expressing human colon cancer (WiDr) in athymic mice. Growth curve analysis, antibody localization, and dose estimation studies were performed. A significant tumor growth delay, measured as the time to reach 1.0 g, was noted for animals receiving specific anti-carcinoembryonic antigen 90Y-MAb (ZCE025, 120 microCi) plus IFN-gamma (61.8 days) as compared to animals that received specific 90Y-MAb with phosphate-buffered saline (34.9 days; P less than 0.005). IFN-gamma (100,000 units) was given i.p. every 8 h for 2 days before and 4 days after 90Y-MAb therapy. The time required to reach 1.0 g for animals treated with nonspecific 90Y-MAb (ZME018) was significantly less either with (38.3 days) or without (34.4 days) IFN-gamma. The difference was more apparent when compared to animals receiving IFN-gamma alone (30.0 days) or phosphate-buffered saline alone (28.9 days; P less than 0.001). Increased antibody localization in the tumors of animals treated with IFN-gamma plus specific 90Y-MAb (43.2% injected dose/g) was seen in comparison to animals treated with specific 90Y-MAb without IFN-gamma (18.2% injected dose/g). The estimate of radiation dose delivered to the tumors, based on biodistribution data over time, revealed significantly higher levels in animals treated with specific 90Y-MAb with IFN-gamma (2477 cGy) compared to animals treated without IFN-gamma (1217 cGy). These results provide support for the use of gamma-interferon as an immunomodulating agent prior to radioimmunotherapy.

Carcinoembryonic antigen expression of resurgent human colon carcinoma after treatment with therapeutic doses of 90Y-alpha-carcinoembryonic antigen monoclonal antibody.

We have previously shown that the colon carcinoma (LS174T) xenografts that emerged shortly after radioimmunotherapy with 90Y-labeled anti-CEA monoclonal antibody (MAb) ZCE025 lacked significant expression of CEA in comparison with the untreated tumors. The present study was designed to establish if the immunophenotype of the treated tumors was the result of CEA specific therapy and if the effect was permanent. Athymic mice bearing LS174T tumors were treated either with 120 mu Ci of 90Y-ZCE025, an equal dose of 90Y-96.5 (nonspecific MAb), or received no treatment. When the treated tumors grew to approximately 1.5 cm in diameter (6 weeks after therapy), they were resected and aliquoted to be transplanted to other mice, plated in tissue culture, fixed in formalin, and homogenized for CEA quantitation. The procedure was repeated 3 times (a total of 4 months after treatment). The CEA content was evaluated 2 and 6 weeks after therapy and when the tumors were transplanted. We confirmed a 4-fold decrease of CEA in the resurgent tumors 6 weeks after specific 90Y-ZCE025 therapy, which was twice the decrease experienced by the tumors treated with nonspecific 90Y-96.5, indicating substantial and specific killing of CEA-expressing cells. The CEA content slowly but progressively increased with each new pass of the tumor in the mice, reaching approximately one-half the value of the controls at the end of the study. The resurgent tumors were also studied by immunohistochemistry with MAbs detecting different epitopes of CEA, keratin, TAG-72, and epithelial membrane antigen to evaluate possible additional immunophenotypic changes induced by radioimmunotherapy. Only the expression of TAG-72 (recognized by MAb B72.3) increased immediately after therapy, but it returned to the original levels by the end of the study. These results suggest that: (a) specific radioimmunotherapy with 90Y-ZCE025 selectively kills cells that express higher levels of CEA; (b) the immunophenotype of the surviving fraction of the tumor appears to slowly revert to its original form; and (c) other tumor markers unrelated to CEA can also be affected. These observations have important implications for the design of radioimmunotherapy trials.

Effects of recombinant human gamma-interferon on carcinoembryonic antigen expression of human colon cancer cells.

The effects of human recombinant gamma-interferon (gamma-IFN) on the levels of carcinoembryonic antigen (CEA) expression were investigated in vitro in three human colon adenocarcinoma cell lines (WiDr, HT29, and SW403). Subconfluent cultures were exposed continuously to IFN at concentrations of 1-1,000 antiviral units/ml for up to 6 consecutive days. IFN resulted in a significant increase in CEA levels when assayed by cellular enzyme-linked immunosorbent assay (ELISA), with higher concentrations and longer exposure times resulting in greater CEA enhancement. A three to five-fold enhancement of CEA was observed after 5-6 days of continuous exposures at concentrations of 100-1,000 antiviral units/ml. CEA levels returned to baseline over a 4-day period after discontinuation of IFN. Levels of IFN that resulted in CEA enhancement also resulted in cell growth inhibition, with a direct correlation observed. Flow cytometric studies, which evaluated changes in CEA membrane expression of only the viable cells remaining after IFN exposure, gave similar results to cellular ELISA. Quantitative CEA ELISA, which quantitated changes in total cellular CEA content, demonstrated greater increase in CEA than predicted by cellular ELISA. Continuous IFN exposures for 5-6 days at 1,000 U/ml led to a 96-, 26-, and 5-fold increase in total CEA for the WiDr, HT29, and SW403 cell lines, respectively. WiDr cells exposed to daily 6-h IFN pulses demonstrated intermediate increases in CEA compared with cells exposed continuously to IFN.(ABSTRACT TRUNCATED AT 250 WORDS)

Gamma-interferon enhancement of carcinoembryonic antigen expression in human colon carcinoma xenografts.

Athymic nu/nu mice bearing a subcutaneous human colon cancer xenograft (WiDr, low CEA expression) were treated with gamma-interferon (gamma IFN) at varying doses, frequencies, and periods of duration. CEA content (micrograms/g) and uptake of radiolabeled anti-CEA monoclonal antibody (MAB) (percent injected dose per gram, % ID/g) were measured at 48 h following administration of the MAB, The optimal enhancement of tumor CEA content and tumor localization of [111In] anti-CEA monoclonal antibody (MAB) was seen at gamma IFN doses of 100,000 U i.p. every 8 h for 4 days (4.7 micrograms/g; 29% ID/g) compared to control animals (0.9 micrograms/g; 10% ID/g). The effects of gamma IFN on CEA content and MAB localization were less pronounced when administered (a) at lower doses: 5,000 to 50,000 U i.p. every 8 h, (b) at varying frequencies: 300,000 U/day delivered in divided doses every 4 or 24 h, or (c) for varying periods: 2 or 6 days of therapy. In each case, the biologic effects on tumor CEA content and uptake of [111In]MAB correlated closely with the serum gamma IFN level. Therefore, we conclude that enhancement of in vivo CEA expression by gamma IFN may have clinical relevance for tumor imaging and therapy using radiolabeled monoclonal antibodies.

Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts.

Radioimmunotherapy and external beam radiotherapy were compared in a nude mouse human colon cancer model. Radioimmunotherapy was delivered by intraperitoneal injection of 90Y-labeled anticarcinoembryonic antigen monoclonal antibody (anti-CEA MAB). Single fraction external beam radiotherapy was delivered using a 60Co teletherapy unit. Control groups received saline, unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody. Subcutaneous CEA-expressing LS174T human colon carcinoma tumors were measured over time. Tumor growth suppression was expressed as delay to reach 2g compared to saline controls. Unlabeled anti-CEA monoclonal antibody and labeled nonspecific monoclonal antibody had no effect. External beam radiotherapy of 300, 600, 1000 and 2000 cGy produced growth delays of 3, 12, 17, and 22 days, respectively. Radioimmunotherapy with 120 microCi, 175 microCi, and 225 microCi resulted in growth delays of 20, 34, and 36 days. Estimated absorbed tumor dose was 1750 cGy in the 120 microCi group. Similar comparisons were done with the more radioresistant WiDr human colon carcinoma cell line. External beam radiotherapy doses of 400, 800, 1200, and 1600 cGy resulted in growth delays of 6, 21, 36 and 48 days, respectively. Radioimmunotherapy of 120 microCi and 175 microCi resulted in growth delays of 9 and 19 days, respectively. The 120 microCi dose delivered an estimated absorbed tumor dose of 1080 cGy to WiDr tumors. In summary, for the radiosensitive LS174T line, radioimmunotherapy produced biologic effects that were comparable to a similar dose of single fraction external beam radiotherapy. For the more radioresistant WiDr tumor, radioimmunotherapy produced a biologic effect which was less than a similar dose of single fraction external beam radiotherapy. These studies suggest that a tumor's response to radioimmunotherapy relative to that of external beam radiotherapy is, in part, dependent on tumor radiosensitivity and repair capacity.

Intraoperative gamma detection probe with presurgical antibody imaging in colon cancer.

In this study, presurgical gamma camera imaging and an intraoperative gamma detection probe were used in 12 consecutive patients 6 to 22 days after infusion with indium 111-labeled anticarcinoembryonic antigen monoclonal antibody (111In-MoAb). In three of 11 patients who underwent laparotomy, clinical management was affected by the probe findings: localization of occult retroperitoneal disease, identification of an occult cecal lesion, and localization of residual disease at a site of local recurrence. Of all intra-abdominal lesions seen using any method, the probe identified 18 (86%) of 21, compared with 14 (67%) of 21 with the 111In-MoAb scan, 10 (48%) of 21 by computed tomographic scan, and 16 (76%) of 21 after surgical exploration. Uptake of 111In-MoAb in the portal (n = 3) and mediastinal (n = 3) lymph nodes was not associated with histologic findings of malignant neoplasms. For all pathologically confirmed extrahepatic and nonportal sites of cancer, the probe localized nine of nine, compared with five of nine by 111In-MoAb scan, two of nine by computed tomographic scan, and six of nine by surgical exploration. Important clinical uses of the intraoperative probe included occult lesion identification, localization of areas with 111In uptake shown with MoAb scanning, and verification of complete resection of areas with 111In-MoAb uptake.

A technical analysis of an intraoperative radiation detection probe.

A technical evaluation was made of a commercial intraoperative radiation probe. This device utilizes a CsI (T1) scintillation detector and light pipe arrangement to count gamma radiation in vivo. After determining the optimal window and threshold setting, additional evaluations included linearity, distance response function, detector dead time, counter reproducibility, detector sensitivity, angular resolution, and energy resolution. Detector dead time (21.2 microseconds) was found to be characteristic of a nonparalysable system. Activity response for each radionuclide was linear (R = 0.99) both with and without collimation. Energy resolution, 25% at 210 keV, was not sufficient to separate the two photons (172 and 247 keV) emitted by 111In. Detector sensitivity was 1136 and 626 counts per s per microcurie of 111In and 99mTc, respectively. The mean effective distance from the face of the uncollimated probe to the crystal was determined to be 2.03 cm in air.

Depression of spontaneous and ionophore-induced transmitter release by ruthenium red at the neuromuscular junction.

The effects on spontaneous and ionophore-induced transmitter release of the inorganic dye, ruthenium red (RuR), a known inhibitor of calcium binding sites, were observed at the frog sartorius neuromuscular junction using intracellular recording techniques. Both crude and purified RuR, at concentrations of 1 and 5 micron depressed or blocked spontaneous release of acetylcholine (ACh) and reduced postsynaptic sensitivity to ACh, the crude dye being more potent than the pure. Pretreatment of muscles with RuR prevented the catastrophic reaction of junctions to 100 micron X537A ionophore. Increased levels of Ca2+ restored spontaneous transmitter release to control levels after depression or blockade by RuR. It was concluded that RuR blocks a critical membrane-bound binding site for calcium which is necessary for quantal release of transmitter.

Radiation safety with breast sentinel node biopsy.

BACKGROUND: Sentinel lymph node biopsy with Technetium 99m sulfur colloid (Tc99m) is an evolving technique that offers the potential for improved staging of breast cancer with decreased morbidity. However, the use of radioactive materials in the operating room generates significant concern about radiation exposure. The purpose of this study was to evaluate radiation exposure to operating room personnel, pathologist, and equipment from specimens during breast sentinel lymph node biopsy. METHODS: Twenty patients were injected with 0.7 to 1.1 mCi of Tc99m sulfur colloid 1.5 to 3 hours before sentinel lymph node biopsy. A calibrated Geiger counter was used to measure dose rates from the breast injection site before skin incision (n = 20), lumpectomy specimens (n = 8), and sentinel nodes (n = 20) at distances of 3, 30, and 300 cm. This represented exposure to the surgeon's hands, surgeon's torso, and scrub nurse, respectively. Exposure to the pathologist's hands and torso was represented as dose-rate measurements from lumpectomy and nodal specimens. The operative instruments, trash receptacles, suction canisters, pathology slides, and cryostat machines were measured at 3 cm at the conclusion of each procedure. Specimens or equipment emitting radiation doses equal to background levels (0.04 mRem/h) were exempt from special handling and disposal. RESULTS: The highest exposure rate was to the surgeon's hands from the breast injection site before skin incision (34.25 mRem/h). Exposure to the surgeon's torso measured 1.33 mRem/h, and exposure to the scrub nurse's torso measured 0.15 mRem/h from the injection site. Exposure to the pathologist's hands was 18.62 and 0.06 mRem/h from the lumpectomy specimen and sentinel node, respectively. Exposure to the pathologist's torso measured 0.34 and 0.04 mRem/h from the lumpectomy specimen and sentinel node, respectively. One hundred percent of lumpectomy specimens measured above the exempt level. Thirty-two of 46 (70%) sentinel lymph nodes emitted radiation equal to the exempt background level. Seventeen of 20 trash receptacles (85%) and 4 of 12 (33%) suction canisters measured equal to background levels. All operative instruments, pathology slides, and cryostat machines were equal to background levels. CONCLUSIONS: Radiation exposure to operating room personnel, pathologists, and operative equipment during a breast sentinel node biopsy using Tc99m is minimal. A primary surgeon can perform 2,190 hours, a scrub nurse 33,333 hours, and a pathologist 14,705 hours of procedural work before surpassing Occupational Safety and Health Administration limits. Operative instruments, pathology slides, and cryostat machines do not require special handling. All lumpectomy specimens should be stored for decontamination until the dose rate equals background levels. Intraoperative dose-rate monitoring allows selective decontamination of nodal specimens, trash receptacles, and suction canisters, which decreases disposal time and cost.

The role of computed tomography in the diagnosis of acute appendicitis.

BACKGROUND: Routine contrast-enhanced computed tomography (CECT) has been described as an accurate diagnostic imaging modality in patients with acute appendicitis. However, most patients with acute appendicitis can be diagnosed by clinical findings and physical exam alone. The role of CECT in patients suspected of having appendicitis but with equivocal clinical exams remains ill defined. METHODS: One hundred and seven consecutive patients who were thought to have appendicitis but with equivocal clinical findings and/or physical exams were imaged by CECT over a 12-month period. Oral and intravenous contrast-enhanced, spiral abdominal and pelvic images were obtained using 7-mm cuts. CECT images were interpreted by a board-certified radiologist. Main outcome measures included CECT sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy in the diagnosis of acute appendicitis, comparing CECT with ultrasound, and determining the impact of CECT on the clinical management of this patient population. RESULTS: A group of 107 patients consisting of 44 males (41%) and 63 females (59%) with a median age of 33 years (range 13 to 89 years) were imaged with CECT to evaluate suspected appendicitis. Of the 107 CECTs performed, 11 false-positive and 3 false-negative readings were identified, resulting in a sensitivity of 92%, specificity of 85%, PPV of 75%, NPV of 95%, and an overall accuracy of 90%. Forty-three patients were imaged with ultrasound and CECT, and CECT had significantly better sensitivity and accuracy (30% versus 92% and 69% versus 88%, P<0.01). With regard to clinical management, 100% (36/36) of patients with appendicitis, and 4.2% (3/71) of patients without appendicitis underwent appendectomy. Therefore, the overall negative appendectomy rate was 7.6% (3/39). CONCLUSIONS: CECT is a useful diagnostic imaging modality for patients suspected of having acute appendicitis but with equivocal clinical findings and/or physical exams. CECT is more sensitive and accurate than ultrasound and is particularly useful in excluding the diagnosis of appendicitis in those without disease.

Cryosurgical ablation of hepatic tumors.

BACKGROUND: Cryosurgical ablation of hepatic tumors relies on nonspecific tissue necrosis due to freezing as well as microvascular thrombosis. Patients with selected primary and metastatic hepatic malignancies who are not candidates for surgical resection are afforded potentially curative benefit using this technique. METHODS: Forty patients underwent cryosurgery for hepatic malignancy related to colorectal metastasis (n = 27), hepatocellular carcinoma (n = 8), metastatic breast (n = 2), metastatic neuroendocrine (n = 2), and metastatic ovarian carcinoma (n = 1). Intraoperative ultrasound (IOUS) was used in all patients to help locate the tumor and guide the cryosurgical trocar to the lesions. RESULTS: Indications for cryosurgical ablation included bilobar and centrally located disease, poor medical risk, insufficient hepatic reserve, and involved margin after wedge resection. Major complications included hepatic parenchyma cracking requiring transfusion in 5 patients, 1 postoperative biliary stenosis, and 1 inferior vena cava injury. There were 3 postoperative deaths from non-hepatic-related events. Based on Kaplan-Meier analysis the estimated overall survival for patients with hepatocellular carcinoma (60% at 18 months) was compared with patients with colorectal metastases (30% at 18 months). Nine patients (23%) are currently free of disease with an average follow-up of 17.7 months. The pattern of failure was identified at the site of cryosurgical ablation in 2 of 88 lesions. CONCLUSIONS: Cryosurgical ablation of selected hepatic malignancies is a safe and viable treatment for patients not amenable to surgical resection.

Sentinel lymph node biopsy for melanoma.

BACKGROUND: The most powerful predictor of survival for patients with melanoma is the status of the regional lymph nodes. Sentinel lymph node biopsy may provide improved staging accuracy without the morbidity of elective lymph node dissection (ELND). METHODS: Sixty-eight patients with intermediate thickness melanoma underwent gamma probe guided sentinel node biopsy without ELND and were followed up over a mean of 22 months. RESULTS: A sentinel node was found in all patients. Six patients (9%) had positive sentinel nodes; all underwent complete lymphadenectomy. Two patients (3%) with negative sentinel nodes developed nodal recurrence; 1 of these patients was found to have microscopic disease on reexamination of the sentinel node. Two patients (3%) developed systemic disease. CONCLUSION: Gamma probe guided sentinel node biopsy can be performed with a high rate of technical success. It provides accurate pathological staging with a low incidence of nodal basin failure.

Cryotherapy for liver tumors.

The curative management of primary and metastatic liver tumors has traditionally relied on surgical resection. Unfortunately, fewer than 10% of newly diagnosed patients have tumors that are considered to be surgically resectable. Limitations that often preclude a safe surgical resection include bilobar or centrally located tumors, insufficient hepatic reserve, cirrhosis, and/or associated comorbid medical conditions. For individuals with unresectable hepatic tumors, the treatment options are few, and the prognosis is uniformly poor. However, cryosurgery is a promising therapeutic alternative for these patients. This rapidly emerging technology allows for image-guided in situ tumor eradication using subzero temperatures, while selectively sparing most normal hepatic tissue. Tumor death occurs by direct cellular freezing and indirectly through vascular thrombosis and tissue anoxia. Accumulating data suggest that cryosurgery is a safe, effective treatment option for patients who would otherwise fair quite poorly, and that it may achieve long-term survival rates similar to those observed with formal surgical resection. This article summarizes the role cryosurgery may play in the management of patients with surgically unresectable primary and metastatic liver tumors.

Hepatic imaging with iron oxide magnetic resonance imaging.

The management of hepatic tumors presents a challenging problem. The natural history of primary and metastatic liver lesions portends a poor prognosis. However, surgical resection and newer ablative techniques have had a great impact on cure rates. Unfortunately, the majority of newly diagnosed patients have surgically unresectable disease. Advances in hepatic imaging have improved the preoperative evaluation of malignant lesions and greatly assisted in selecting patients for surgical resection or other interventions. Currently, a number of modalities are available for the evaluation of hepatic tumors. This article provides an overview of some of the modalities currently in use, examines the role of iron oxide magnetic resonance imaging (MRI), and relates experience with its use at Baylor University Medical Center.

Gene therapy for head and neck cancers.

Despite advances in surgery, radiotherapy, and chemotherapy, survival of patients with squamous cell carcinoma of the head and neck has not significantly improved over the past 30 years. Locally recurrent or refractory disease is particularly difficult to treat. Repeat surgical resection and/or radiotherapy are often not possible, and long-term results for salvage chemotherapy are poor. Recent advances in gene therapy have been applied to recurrent squamous cell carcinoma of the head and neck. Many of these techniques are now in clinical trials and have shown some efficacy. This article discusses the techniques employed in gene therapy and summarizes the ongoing protocols that are currently being evaluated in clinical trials.

Diagnostic evaluation of hepatocellular carcinoma in a cirrhotic liver.

Hepatocellular carcinoma (HCC) is one of the world's most common cancers. It is closely associated with cirrhosis, especially that due to viral hepatitis. The incidences of viral hepatitis and HCC are rising steadily in the United States. When symptomatic, HCC is usually unresectable and associated with a median survival of less than 6 months. Nodular lesions of undetermined malignant potential are often found in cirrhotic, explanted livers. There appears to be a continuum of increasing malignant potential from regenerating nodules to dysplastic nodules and to HCC. Pathologic differentiation of high-grade dysplastic nodules from HCC is often difficult. Early diagnosis offers the best potential for curative intervention. Screening of high-risk patient populations using serum alpha-fetoprotein and ultrasound has been attempted but is hindered by low sensitivity and specificity. The multinodularity and vascular flow anomalies of the cirrhotic liver complicate imaging. However, recent advances in magnetic resonance imaging technology allow for more accurate examination of the liver. We review the current status of hepatic imaging techniques and the results of screening a high-risk population for HCC.

Acute renal failure in the outpatient setting.

With the ever-increasing pressures for outpatient diagnostics and therapeutics, one must be increasingly alert to the occurrence and consequences of acute renal failure. The significance of minor increases in the serum creatinine level must be recognized, so that modifications of drug therapy can be made and correction of possibly life-threatening electrolyte imbalances can be undertaken. The multiple drug-related renal syndromes must be considered when initiating therapy with any medication. Prophy, laxis for acute renal failure with saline solution, mannitol, and/or furosemide should be considered in patients at increased risk.