Evaluation of polymerase chain reaction assays for the diagnosis of Trichomonas vaginalis infection in Russia.

BACKGROUND: In Russia, the microscopy- and culture-based diagnostics of trichomoniasis is mainly suboptimal. Recent years, domestically produced diagnostic PCR assays have been implemented; however, any evaluation of these PCRs has never been internationally reported. OBJECTIVE: To assess the performance characteristics of PCR assays developed and currently used in Russia to detect Trichomonas vaginalis. MATERIALS AND METHODS: Five PCR assays were assessed on 448 samples (317 vaginal and 131 male urethral) collected from symptomatic attendees of youth centres (n = 415) and patients of a dermatovenereological dispensary that were previously diagnosed with trichomoniasis (n = 33). As reference assay, a sensitive and specific real-time multiplex PCR was used. RESULTS: T. vaginalis DNA was detected in five (all females) of the 415 patients of youth centres (1.2%). All 33 patients previously diagnosed at the venereological dispensary proved to be true positive. For 445 (99.3%) of these 448 samples identical results were obtained by all PCRs, 35 positive and 410 negative. The three discordant samples were positive in all PCRs except one conventional PCR assay. The sensitivities of the PCRs were 94.3-100% and 66.7-100% for vaginal and urethral swabs, respectively. All evaluated assays were 100% specific. The detection limits of the different PCRs ranged from 0.1 to 5 genome equivalents per reaction. CONCLUSION: The PCR assays currently used in Russia for the detection of T. vaginalis have in general high sensitivities and excellent specificities for both vaginal samples and urethral samples from males.

A real-time quadriplex PCR assay for the diagnosis of rectal lymphogranuloma venereum and non-lymphogranuloma venereum Chlamydia trachomatis infections.

OBJECTIVES: To develop and evaluate a real-time quadriplex PCR for the diagnosis of lymphogranuloma venereum (LGV) and non-LGV chlamydial infections using rectal swab specimens. METHODS: The design of the real-time quadriplex PCR assay incorporates an LGV-specific, a non-LGV-specific target sequence, a Chlamydia trachomatis plasmid target, and the human RNase P gene as an internal control. The performance of the quadriplex PCR was compared with a previously reported real-time duplex PCR assay on which LGV diagnosis was based on exclusion. RESULTS: Very good agreement (85 of 89 specimens, 95.5%) was found between the two multiplex PCR assays for the detection of C trachomatis DNA (kappa value 0.93, 95% CI 0.86 to 0.99). Both assays identified 34 LGV, 35 non-LGV C trachomatis and 16 negative specimens. Of two specimens that tested positive for non-LGV by the duplex PCR, one was found to be a mixed infection and the other was positive only for plasmid and RNase P targets by the quadriplex PCR. Two additional specimens that had equivocal results for non-LGV by the duplex PCR also tested positive only for plasmid target and human DNA by the quadriplex PCR. In addition, six specimens that tested negative by the duplex PCR assay were found to be invalid when using the quadriplex PCR. CONCLUSIONS: A real-time quadriplex PCR assay has been developed that is capable of detecting LGV, non-LGV, or mixed infections simultaneously in rectal specimens. The assay also contains a supplemental amplification target for the confirmation of C trachomatis infection as well as a human DNA control for monitoring sample adequacy and PCR inhibition.

Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: A previous meta-analysis investigated the role of chemotherapy in head and neck locally advanced carcinoma. This work had not been performed on nasopharyngeal carcinoma. OBJECTIVES: The aim of the project was to study the effect of adding chemotherapy to radiotherapy on overall survival (OS) and event-free survival (EFS) in patients with nasopharyngeal carcinoma. SEARCH STRATEGY: We searched MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2003) and trial registers. Handsearches of meeting abstracts, references in review articles and of the Chinese medical literature were carried out. Experts and pharmaceutical companies were asked to identify trials. SELECTION CRITERIA: Randomised trials comparing chemotherapy plus radiotherapy to radiotherapy alone in locally advanced nasopharyngeal carcinoma were included. DATA COLLECTION AND ANALYSIS: The meta-analysis was based on updated individual patient data. The log rank test, stratified by trial, was used for comparisons and the hazard ratios (HR) of death and failure (loco-regional/distant failure or death) were calculated. MAIN RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis was performed including 11 comparisons based on 1975 patients. The median follow up was six years. The pooled hazard ratio of death was 0.82 (95% confidence interval (CI) 0.71 to 0.95; P = 0.006) corresponding to an absolute survival benefit of 6% at five years from chemotherapy (from 56% to 62%). The pooled hazard ratio of tumour failure or death was 0.76 (95% CI 0.67 to 0.86; P < 0.00001) corresponding to an absolute event-free survival benefit of 10% at five years from chemotherapy (from 42% to 52%). A significant interaction was observed between chemotherapy timings and overall survival (P = 0.005), explaining the heterogeneity observed in the treatment effect (P = 0.03) with the highest benefit from concomitant chemotherapy. AUTHORS' CONCLUSIONS: Chemotherapy led to a small but significant benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with radiotherapy.

Radiation therapy versus chemotherapy as initial treatment for localized nasal natural killer (NK)/T-cell lymphoma: a single institute survey in Taiwan.

BACKGROUND: To clarify the role of intention to treat for patients with localized nasal natural killer (NK)/T-cell lymphoma, and to determine the prognostic factors for these patients. PATIENTS AND METHODS: We conducted a retrospective review of 46 patients with localized nasal NK/T-cell lymphomas treated at a single institute between January 1988 and July 2002. RESULTS: The type of intended treatment was a significant factor for overall survival (OS) (5-year OS: RT versus CT = 83.3% versus 28.6%, P = 0.0269) or failure-free survival (FFS) (5-year FFS: RT versus CT = 83.3% versus 27.1%, P = 0.0247). In the intended chemotherapy group, salvage with radiotherapy was superior to chemotherapy alone for OS (5-year OS: 42.2% versus 20.0%, P = 0.0252) or FFS (5-year FFS: 41.0% versus 20.0%, P = 0.0352). On multivariate analysis, both N stage and serum lactate dehydrogenase level were independent factors for OS and FFS. No radiotherapy was an independent adverse factor for OS; advanced T stage and more than one extranodal involvement were independent adverse factors for FFS. CONCLUSIONS: Patients with localized nasal NK/T-cell lymphomas were better managed with radiotherapy as front-line therapy. The advantage of radiotherapy persisted even as palliative therapy after chemotherapy.

Thymoma is associated with an increased risk of second malignancy.

BACKGROUND: An association between thymoma and second malignancy has been suggested but has not been validated. Whether the relation is due to treatment or to other thymoma-associated conditions is unclear. METHODS: The authors studied 192 consecutive patients with thymoma and compared the incidence of second malignancies with those of 206 patients who underwent thymectomy for nonthymomatous conditions and 1426 patients with nasopharyngeal carcinoma (NPC). Detailed clinicopathologic features of thymoma patients with second malignancies were described. RESULTS: Additional malignancies were detected in 15 of 192 patients (8%) during their clinical courses. The risk for those patients was significantly greater compared with the risk for patients with nonthymomatous conditions (adjusted odds ratio [OR], 3.81; 95% confidential intervals [95%CI], 1.05-13.81; P = 0.042) and patients with NPC (adjusted OR, 4.89; 95%CI, 2.26-10.53; P < 0.0001) after adjustment for age, gender, length of follow-up, myasthenia gravis, and radiation therapy. The occurrence of second malignancies did not correlate with histologic type or stage of thymoma, radiation therapy, or myasthenia gravis. CONCLUSIONS: Thymoma is associated with an increased risk of second malignancy. The association cannot be attributed to the effect of thymectomy or radiation therapy. Patients with thymoma, even if it is benign, should be followed regularly to facilitate the early detection of other malignancies.

The clinical features and prognostic factors of hepatocellular carcinoma patients with spinal metastasis.

OBJECTIVE: Hepatocellular carcinoma is the most common malignancy in Taiwan, and spinal metastasis is a serious complication in cancer patients. In this study, we aimed to delineate the clinical features, evaluate the radiotherapy response and analyse the prognostic features in hepatocellular carcinoma subjects with spinal metastasis. METHODS: From 1981 to 1997, 102 patients with spinal metastasis were enrolled, taken from the 5887 documented hepatocellular carcinoma patients treated at Taipei Veterans General Hospital. All the clinical and laboratory data were recorded, including: age; gender; liver biochemistry; tumour characteristics; Child-Pugh's score; performance status; number and location of vertebral metastasis; motor capacity; neurological symptoms and signs; response to radiotherapy of the spinal lesion; and survival. Prognostic factors in hepatocellular carcinoma patients with spinal metastasis were analysed using Cox's regression model. RESULTS: The most common symptoms in hepatocellular carcinoma patients with spinal metastasis were lower back pain (74.5%), thoracic numbness (52.9%) and lower limb weakness (51.0%). Of the 102 patients, 84 received palliative radiotherapy using 3000 cGy for spinal lesions. Of these 84 patients, 32.1% showed a complete response, 26.2% a partial response and 41.7% a non-response to the radiotherapy. Multivariate Cox's regression analysis revealed that responsive radiotherapy (complete response + partial response) and good performance status (score

The triple-phase CT image appearance of post-irradiated livers.

OBJECTIVE: To evaluate the sequential CT appearance of the liver after hepatic irradiation and to investigate the correlation between CT findings and radiation-induced hepatic injury. MATERIAL AND METHODS: The triple-phase CT images of 18 patients with hepatocellular carcinomas (HCC) after hepatic irradiation were retrospectively reviewed (in total 41 CT studies). The high-dose region within the liver was defined as the area receiving more than 90% of the prescribed irradiation dose. The mean radiation dose was 55.5 Gy. Density changes and patterns of enhancement in the high-dose region were classified as three types: type I, constant low-density change in all phases; type II, low-density change in both pre-contrast and arterial phases, and iso-density change in the portal phase; type III, low- or iso-density change in the pre-contrast phase, low- or high-density change in the arterial phase, and persistent high-density change in the portal phase. The interval between completion of radiotherapy and the CT examinations ranged from 9 to 469 days, with a mean of 147 days. RESULTS: Nine of the 41 CT studies presented with type I, 9 with type II, and 16 with type III CT findings. The mean interval between completion of radiotherapy and the appearance of types I, II, and III CT findings were 74, 183, and 220 days, respectively. The interval was significantly shorter for type I findings than for type II and type III. The difference in interval was not significant between type II and type III. A type I finding with constant low-density change in the high-dose region of the liver was the most common pattern of CT findings within the first 3 months after hepatic irradiation. Either types II or III findings were frequently seen after 3 months. CONCLUSION: The sequential CT appearance and the density changes may indicate correlation with the pathogenesis of veno-occlusive disease.

Ceramide inhibits lipopolysaccharide-mediated nitric oxide synthase and cyclooxygenase-2 induction in macrophages: effects on protein kinases and transcription factors.

The goal of this study was to elucidate whether triggering the sphingomyelin pathway modulates LPS-initiated responses. For this purpose we investigated the effects of N-acetylsphingosine (C(2)-ceramide) on LPS-induced production of NO and PGE(2) in murine RAW 264.7 macrophages and explored the signaling pathways involved. We found that within a range of 10-50 microM, C(2)-ceramide inhibited LPS-elicited NO synthase and cyclooxygenase-2 induction accompanied by a reduction in NO and PGE(2) formation. By contrast, a structural analog of C(2)-ceramide that does not elicit functional activity, C(2)-dihydroceramide, did not affect the LPS response. The nuclear translocation and DNA binding study revealed that ceramide can inhibit LPS-induced NF-kappaB and AP-1 activation. The immunocomplex kinase assay indicated that IkappaB kinase activity stimulated by LPS was inhibited by ceramide, which concomitantly reduced the IkappaBalpha degradation caused by LPS within 1-6 h. In concert with the decreased cytosolic p65 protein level, LPS treatment resulted in rapid nuclear accumulation of NF-kappaB subunit p65 and its association with the cAMP-responsive element binding protein. Ceramide coaddition inhibited all the LPS responses. In addition, LPS-induced PKC and p38 mitogen-activated protein kinase activation were overcome by ceramide. In conclusion, we suggest that ceramide inhibition of LPS-mediated induction of inducible NO synthase and cyclooxygenase-2 is due to reduction of the activation of NF-kappaB and AP-1, which might result from ceramide's inhibition of LPS-stimulated IkappaB kinase, p38 mitogen-activated protein kinase, and protein kinase C.

Phase II trial of systemic recombinant interleukin-2 in the treatment of refractory nasopharyngeal carcinoma.

BACKGROUND: Interleukin-2 (IL-2) is a cytokine produced by activated T cells, which has shown powerful immunostimulatory and antineoplastic properties. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated cancer with abundant lymphocyte infiltration histologically. The activity of IL-2 in the treatment of NPC patients is currently unknown. A phase II study was, therefore, initiated to evaluate the efficacy, toxicity and immunological consequences of intravenous bolus IL-2 in patients with recurrent/metastatic NPC. METHODS: Between November 1996 and April 1997, 14 patients with recurrent/metastatic NPC were entered into the study. Recombinant IL-2 (Proleukin, Chiron) was injected by intravenous bolus every 8 h at 72,000 IU/kg for a maximum of 15 doses. After 7 days, patients were retreated with a second identical cycle of therapy. Those patients who were stable or responding to treatment 5-6 weeks later went on to receive another course (two cycles) of therapy. All patients received prophylactic antibiotics and antipyretic medicine. Response and toxicities were evaluated. Serial plasma level of TNF-alpha, IL-6, soluble IL-2 receptor, IL-10 and soluble CD8 were determined. RESULTS: Fourteen patients received a total of 34 cycles of therapy. No response was observed. Fifty percent had stable disease, 50% had progressive disease after a median of two cycles of therapy. There was one treatment-related death from acute myocardial infarction. Body weight increase (>5%) occurred in 80% of cycles, and hypotension (BP <80 mm Hg systolic) occurred in 53%. Serum creatinine increase (>2 mg%) occurred in 24% of cycles, and SGOT/SGPT increase (>3x) in 10% of cycles. Symptoms of somnolence, general malaise, nausea and vomiting, pruritus, xerostomia, desquamation were generally mild to moderate but rapidly reversible. CONCLUSION: The single modality of intravenous bolus IL-2 at the dose level of 72,000 IU/kg is clinically ineffective in NPC patients. Potential mechanisms of the ineffectiveness of IL-2 therapy on NPC patients are discussed.

Preclinical evaluation of locoregional delivery of radiolabeled iododeoxyuridine and thymidylate synthase inhibitor in a hepatoma model.

UNLABELLED: We report improved incorporation of the radiolabeled-thymidine analog [125I/131I]5-iodo-2'-deoxyuridine ([125I/131I]IdUrd) into DNA by the addition of Thymitaq, a thymidylate synthase inhibitor, as a strategy of molecular radiotherapy for hepatoma treatment. METHODS: The synergistic effect of combination [125I]IdUrd and Thymitaq in clonogenic survival and DNA incorporation was shown on the human hepatoma cell line Hep3B. Radiobiodistribution of intrahepatic arterially injected [125I]IdUrd and Thymitaq was studied in a rat N1S1 hepatoma model. In vivo therapeutic effects of locoregional delivery of both drugs were evaluated in mouse subcutaneous hepatoma and ascitic hepatoma models. RESULTS: In a clonogenic assay, Thymitaq showed a synergistic effect with [125I]IdUrd but not cold IdUrd. Thymitaq had a dose-dependent modulation effect on DNA-[125I]IdUrd incorporation. The biodistribution study indicated a slower clearance rate of [125I]IdUdR in the hepatoma as well as an initially higher uptake of [125I]IdUrd into DNA when the [125I]IdUrd was combined with Thymitaq. In vivo studies showed a superior therapeutic effect of combination Thymitaq and [125I]IdUrd in both subcutaneous and ascites tumor models, but the combination of [131I]IdUrd and [125I]IdUrd may be more effective than Auger electron emitters alone for the treatment of subcutaneous tumor. CONCLUSION: The strategy of locoregional delivery of [125I/131I]IdUrd to a tumor site through an intrahepatic arterial, intratumoral, or intraperitoneal route in combination with Thymitaq is promising and may also have a favorable therapeutic index in vivo.

Salvage surgery for recurrent nasopharyngeal carcinoma.

OBJECTIVE: To evaluate the efficacy of salvage surgery in the treatment of recurrent nasopharyngeal carcinoma (NPC) at the primary site. STUDY DESIGN: A retrospective investigation of the outcome of salvage surgery for 28 patients with recurrent NPC after definite radiation therapy. METHODS: The nasopharynx was approached anteroposteriorly by the transmaxillary approach (maxillary swing, maxillectomy) or inferior approach (midline mandibulotomy or median labiomandibular glossotomy), or laterally by modified facial translocation or transpterygoid approach; intentional ligation of the internal carotid artery was performed after establishment of extracranial-intracranial (EC-IC) bypass in one patient; postoperative irradiation was given to the patients with positive pathological margins. RESULTS: Nine patients lived without disease for 20 to 93 months (mean interval, 52 mo) after surgery; among them, eight patients had T1 tumors that were resected totally by surgery via anteroposterior approaches and the other patient had postoperative irradiation to control the disease. Seven patients had local recurrence 8 to 21 months after treatment. Four patients developed distant metastases, including one patient with a T2b tumor that was totally resected through modified facial translocation approach with ligation of internal carotid artery. Eight patients died of other causes; internal carotid artery blowout was the cause of death in four of these eight patients. CONCLUSIONS: In most cases of recurrence, T1 nasopharyngeal tumors can be resected totally by anteroposterior approaches; for T2 or larger tumors, postoperative irradiation is usually necessary. Otherwise, facial translocation offers a better chance to completely resect the tumors. Internal carotid artery is better ligated if patients have received greater than 70 Gy irradiation or if the artery must be exposed during the surgery. We suggest that EC-IC bypass be used to avoid the possible complications (or cerebral ischemic stroke) caused by ligation of internal carotid artery. The transmaxillary approach is favored in the management of nasopharyngeal tumor recurrence with nasal cavity extension, and midline mandibulotomy is more suitable for resection of posterior margin of nasopharyngeal tumor recurrence. Facial translocation offers the widest operative field and is the most versatile approach for radical resection of nasopharyngeal tumor recurrence, but the surgeon should be skilled in the management of the facial nerves to reduce morbidity.

Life-threatening haemorrhage from a sternal metastatic hepatocellular carcinoma.

Rupture of the tumour is a catastrophic complication of hepatocellular carcinoma. The prognosis in patients with a ruptured hepatocellular carcinoma is usually unfavourable. We describe a 46-year-old man who suffered from visible massive tumour haemorrhage due to a hepatitis B-related hepatocellular carcinoma that metastasized to the sternal bone. The prominent tumour mass was bulging over the anterior chest wall on the sternum of the patient, and bled spontaneously. This episode of life-threatening haemorrhage was stopped by surgical ligation of the bleeding site. Palliative radiotherapy shrank the tumour mass size and prevented further possible bleeding. This is likely to be the first reported case with a visible spontaneous tumour bleeding from a sternal metastatic hepatocellular carcinoma.

Concomitant chemoradiation treatment in the management of patients with extrahepatic biliary tract recurrence of gastric carcinoma.

BACKGROUND: The aim of this study was to determine the role of concomitant chemoradiation in the alleviation of obstructive jaundice in patients with extrahepatic biliary tract metastases from gastric carcinoma. METHODS: Thirteen patients with good performance status who had obstructive jaundice resulting from extrahepatic biliary metastases after gastrectomy for gastric carcinoma were treated with palliative intent. Treatment consisted of insertion of a percutaneous transhepatic choledochal drainage (PTCD) catheter followed by external radiation up to a total dose of 40-60 grays in combination with chemotherapy (cisplatin 20 mg/m(2)/day, 5-fluorouracil 600 mg/m(2)/day, and leucovorin 90 mg/m(2)/day for 96 hours during the first and fifth weeks) on an outpatient basis. RESULTS: The concomitant chemoradiation produced a good palliative effect in all 13 patients. Hyperbilirubinemia continued to improve after treatment, patients' clay-colored stool resolved within an average of 4 weeks (range, 2-6 weeks), and bilirubin levels returned to normal. The PTCD catheter could be removed after treatment was completed (the seventh week); the mean duration of PTCD placement was 2 months. The entire treatment course was performed on an outpatient basis; hospital admission was necessary only for PTCD insertion and chemotherapy. Ten patients died of their disease, with an average survival of 14.4 months (range, 4-31 months) from the time of PTCD insertion. Three patients are still alive at 16, 21, and 8 months. Biliary tract patency was maintained until death. No serious treatment-related complications occurred, and no endoprothesis or intraluminal brachytherapy was needed in this study. CONCLUSIONS: Satisfactory palliation can be achieved by concomitant chemoradiation for patients with obstructive jaundice resulting from extrahepatic biliary metastases from gastric carcinoma, providing an alternative treatment choice for these patients.

Successful initial treatment with weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin chemotherapy in advanced gastric cancer patients with disseminated intravascular coagulation.

BACKGROUND: Acute disseminated intravascular coagulation (DIC) is a rare but severe complication of gastric adenocarcinoma. Conventional treatments, such as fresh frozen plasma, platelet replacement and heparin injections, are disappointing. The only way to correct this fatal condition is to control the underlying cancer promptly by effective chemotherapy. Here the successful initial control of acute DIC in gastric cancer patients with weekly EEPFL chemotherapy is reported. METHODS: Advanced gastric cancer patients complicated with acute DIC were eligible. Patients were treated with weekly EEPFL therapy (etoposide 40, epirubicin 10, cisplatin 25, 5-fluorouracil 2200 and leucovorin 120 mg/m2 ). Response, survival and toxicity were evaluated. RESULTS: From April 1997 to April 1999, six patients were included in this study. All patients received EEPFL chemotherapy. Clinical and laboratory evidence of acute DIC stabilized quickly after starting chemotherapy. Four patients showed a partial response, one stable disease and one progressive disease. The toxicity was mild and well tolerated. Median survival was 28 weeks (12, 14, 26, 30, 30 and 32 weeks). All patients suffered from a relapse of DIC after initial successful control and died within 30 days of clinical and laboratory evidence of acute DIC relapse. CONCLUSION: EEPFL therapy is an effective chemotherapy regimen for patients with advanced gastric cancer associated with acute DIC. The prognosis is poor if the DIC relapses after the initial successful control.

A novel approach for nasopharyngeal carcinoma treatment uses phenylbutyrate as a protein kinase C modulator: implications for radiosensitization and EBV-targeted therapy.

Sodium phenylbutyrate (NaPB) represent a new non-toxic class of compounds with antiproliferative activities to different tumors and has been shown to modulate many gene expressions by inhibiting histone deacetylation and DNA methylation as the major mechanism. Butyrate and other protein kinase C (PKC) activators have been reported to be able to activate virus enzymes. The present work investigates whether NaPB has an antiproliferative effect or modulatory effects on EBV-associated nasopharyngeal carcinoma (NPC) and whether EBV thymidine kinase gene can be activated to make cells susceptible to ganciclovir (GCV) therapy. NaPB treatment displayed a dose- and time-dependent antiproliferative effect on the NPC cell line CNE2. Cell cycle analysis revealed an inhibitory effect of NaPB on G1-S-phase progression. Shortly after NaPB treatment, we found that PKC activity was activated rapidly but also decreased rapidly. Down-regulation of PKC-alpha and translocation of PKC-alpha from the cytosol to membrane were seen by Western blot. The decrease in PKC activity by NaPB corresponds to an enhanced response to radiation on CEN2 cells. Moreover, NaPB up-regulated EBV thymidine kinase activity to render EBV-associated Daudi cells susceptible to killing by GCV. Based on the observations of NaPB as a PKC modulator, the combination of NaPB, GCV, and radiation may provide a potential novel approach for treatment of EBV-associated NPC.

Salvage surgery for recurrent nasopharyngeal carcinoma in anterior marginal miss after radiotherapy.

Nasopharyngeal carcinoma (NPC) is treated primarily by radiotherapy. Marginal miss after radiotherapy is a potential cause for treatment failure in NPC. Anterior marginal miss after irradiation results in recurrent tumors in the nasal cavity outside the nasopharynx. From 1991 to January 1997, 6 recurrent NPCs arising in the anterior marginal miss zone after radiotherapy were confirmed by pathologic and radiologic evaluation. One patient had infiltrating growth of the original NPC tumor into the anterior part of nasal septum, and the other 5 had microscopic extensions from the original NPC tumors into the nasal cavity that were beyond detection by endoscopy or CT scan. In some cases the tumors extended further to include the hard palate or the lacrimal sac. Medial maxillectomy and partial maxillectomy with or without resection of the hard palate were necessary to encompass the extent of the tumors. Surgical margins were free of cancer cells in 5 patients. No further treatment was given in these 5 patients. Another patient with tumor extending to the lacrimal sac received postoperative radiotherapy. Five of the 6 patients survived with no evidence of disease for 8 to 65 months. One patient had distant metastasis 14 months after surgery but was free from tumor at the primary site. Radical surgery can result in good and sustained local control for anterior marginal miss of NPC after radiotherapy.

Gene therapy with tumor vaccine increases the survival of hepatoma-bearing mice.

BACKGROUND: Tumor vaccines combined with cytokine gene therapy and Bacillus Calmette-Guérin (BCG) were tested for prevention and therapeutic effects in the H6 mouse hepatoma model. METHODS: Plasmid DNA of expression vectors carrying cDNA of mouse interleukin (IL)-2 and mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) were used for transfection to obtain H6 mouse hepatoma cells that secreted IL-2 (H6/IL-2) or GM-CSF (H6/GM-CSF). For tumor prevention, groups of mice were immunized twice with irradiated tumor cells with untransduced H6, H6/IL-2, H6/GM-CSF, or an equal mixture of H6/IL-2 and H6/GM-CSF. Three weeks later, these mice were inoculated subcutaneously with live H6 hepatoma cells, and tumor growth was measured. For therapeutic studies, mice first inoculated with live H6 cells were treated three days later with various irradiated tumor cell vaccines alone or in combination with BCG. Subsequent tumor growth was measured. RESULTS: In tumor prevention studies, significant protection from tumor growth has been observed in animals vaccinated with irradiated cytokine-secreting H6 cells compared with those immunized with irradiated parental H6 cells. In tumor therapy studies, subsequent administration of irradiated H6/GM-CSF cells in combination with BCG impeded the tumorigenicity of preinoculated live H6 hepatoma cells. CONCLUSIONS: These results suggest that cytokine-secreting tumor vaccines have a prophylactic effect and BCG, in combination with irradiated H6/GM-CSF cells, shows a synergistic effect on delaying the growth of H6 mouse hepatomas.

Prognosis of esophageal squamous cell carcinoma: analysis of clinicopathological and biological factors.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is rather common among the Chinese, but the therapeutic outcome is dismal. Knowledge of the prognostic factors in cancerous patients may influence therapeutic strategy. However, systemic analyses of clinicopathological and biological factors for patients with ESCC are few, and the results are controversial. METHODS: Between 1985 and 1996, 117 patients undergoing en bloc esophagectomy and gastric substitution were enrolled. None had neoadjuvant treatment. Postoperative adjuvant therapy was provided for patients at and beyond stages IIa. Clinical responses were followed routinely. Flow cytometry was used to measure DNA ploidy and synthesis-phase fraction (SPF) of the resected esophageal tissues from all patients. Immunohistochemistry was also used to examine the expression of proliferating cell nuclear antigen (PCNA), epidermoid growth factor receptor (EGFR), HER-2/neu, and p53 in the pathological sections. Clinical correlation was evaluated by chi2 with Fisher's exact test, and survival by log-rank test. RESULTS: The overall survival rates were 74% for 1 yr, 48% for 3 yr, and 38% for 5 yr. TNM tumor staging, the number of diseased lymph nodes (N < or = 3 or N > 3), degree of cell differentiation, DNA ploidy, SPF, and lymphovascular invasion were more useful than biological markers, such as PCNA, EGFR, HER-2/neu, and p53, for the prognosis of ESCC. Multivariate analysis revealed significant correlation of tumor staging and number of diseased lymph nodes with patient survival after surgery. CONCLUSIONS: En bloc esophagectomy may provide a rather satisfactory survival rate for patients with early stage ESCC. However, for patients with distant lymph node metastasis and those with more than three lymph nodes involved, radical surgical resection, even combined with postoperative chemoradiotherapy, cannot improve survival. The prognostic value of biological markers, including PCNA, EGFR, HER-2/neu, and p53, however, is limited.

Radiotherapy in the treatment of duodenal bleeding due to hepatocellular carcinoma invasion.

Haemorrhage from an hepatocellular carcinoma (HCC) directly invading the gastrointestinal (GI) tract is uncommon. A 58-year-old man was admitted with upper gastrointestinal (UGI) bleeding and panendoscopy on examination revealed a large duodenal ulcerative bleeding mass. The mass was eventually diagnosed as HCC by pathological examination. The bleeding failed to respond to conventional management of haemostasis, but resolved with an external beam of radiotherapy with a total dose of 6000 cGy over a 5 week period. This unusual presentation of UGI bleeding, due to HCC invading the duodenum and treated by radiotherapy, has not been previously reported.