The usefulness of FDG positron emission tomography for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer: a comparative study with X-ray computed tomography

We evaluated the usefulness of fluorine-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET) in the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer and then compared the findings with the results of X-ray CT by region based on the histological diagnoses. We examined 29 patients with non-small cell lung cancer. One hundred and thirty-two mediastinal lymph nodes were surgically removed and the histological diagnoses were confirmed. FDG PET images, including 146 mediastinal regions, were visually analysed and the mediastinal lymph nodes were scored as positive when the FDG uptake was higher than that in the other mediastinal structures. On the X-ray CT scans, any mediastinal lymph nodes with a diameter of 10 mm or larger were scored as positive. All three examinations were successfully performed on 71 regions. For FDG PET, we found a sensitivity of 76%, a specificity of 98% and an accuracy of 93%. On the other hand, for X-ray CT a sensitivity of 65%, a specificity of 87% and an accuracy of 82% were observed. A significant difference was observed in respect of both specificity and accuracy (P<0.05). Based on the above findings, FDG PET is suggested to be superior to X-ray CT when used for the detection of mediastinal lymph node metastases in patients with non-small cell lung cancer.     

A clinical evaluation of FDG-PET to assess the response in radiation therapy for bronchogenic carcinoma

The clinical usefulness of FDG-PET in the prediction and assessment of response to radiation therapy in patients with bronchogenic carcinoma was evaluated. Thirty patients with untreated bronchogenic carcinoma were included in the study. All patients received FDG-PET before the initiation of radiation therapy, while 20 also received it after completing the therapy. The tumor to muscle ratio (TMR) was used as an index of the FDG uptake. The tumor response to therapy was classified as either a partial response (PR, n = 21) or no change (NC, n = 9) according to changes in the tumor size. Prognosis was made 6 months after the initiation of therapy, and was classified as either relapse (n = 19) or non-relapse (n = 9). The FDG uptakes both before and after therapy were compared with tumor response and prognosis. A high FDG uptake was noted in all 30 lesions before therapy. No significant differences in the uptake before therapy was observed according to the histological types nor T factors (UICC). The lesions with a higher uptake (TMR more than 7) responded better to therapy than those with a lower uptake (p < 0.05). The decrease in the uptake after therapy tended to be more prominent in the PR group than in the NC group. The rate of relapse was higher in lesions with a higher uptake before therapy (TMR more than 10) than in those with a lower uptake. The relapse group also showed a higher uptake after therapy than the non-relapse group. In addition, all 6 lesions showing a higher uptake (TMR more than 5) after therapy eventually relapsed (p < 0.05). Two lesions demonstrating a lower uptake both before and after therapy did not relapse, although no tumor regression due to the therapy was observed. These results indicate that FDG-PET plays a complementary role in both predicting and assessing the therapeutic response and prognosis in patients with bronchogenic carcinoma.     

Evaluation of the Role of Cisplatin-conjugated-soluble Gelatin Sponge: Feasibility Study in a Swine Model

Purpose

To evaluate the safety and the delivery function of cisplatin-conjugated-soluble gelatin sponge in a swine model.

Methods

Fifteen healthy young swine were assigned into three groups: transarterial cisplatin infusion group, transarterial chemoembolization (TACE) with cisplatin-conjugated 120-min soluble gelatin sponge (TACE-120) group, and TACE with cisplatin-conjugated 360-min soluble gelatin sponge (TACE-360) group. A total volume of 0.8 mL/kg cisplatin in each group and 8 mg/kg soluble gelatin sponge in TACE-120 and TACE-360 groups were injected from the left hepatic artery in small increments for 10 min. Common hepatic angiography and whole-blood sampling via the left hepatic vein were conducted to explore recanalization immediately after the procedure and again at 10, 30, 60, 90, 120, 180, 240, 300, 360, and 420 min later. The area under the plasma concentration curve (AUC) of non-protein-bound platinum was compared among the three groups. Each liver was removed and cut into 10-cm-thick sections for calculating liver-damaged volume ratio.

Results

Sequential angiography depicted gradual recanalization of the occluded hepatic artery and total recanalization at 120 and 360 min after embolization in the TACE-120 and TACE-360 groups, respectively. Of the three groups, AUC_0–30, AUC_30–120, and AUC_120–420 were significantly highest in the transarterial cisplatin infusion group (p < 0.001), the TACE-120 group (p < 0.001), and the TACE-360 group (p < 0.001), respectively. The liver-damaged volume ratio in the TACE-360 group was small (8.20 %) but significantly higher than that in the TACE-120 group (2.67 %, p = 0.014).

Conclusion

Cisplatin-conjugated soluble gelatin sponge functions as a cisplatin carrier and is associated with tolerable liver damage.     

Thallium-201 myocardial SPECT findings at rest in sarcoidosis

In 41 patients with sarcoidosis (diagnosed according to criteria recommended by the Committee on Diffuse Pulmonary Disease, Ministry of Health and Welfare, Japan 1988), thallium-201 (²⁰¹Tl) myocardial SPECT was performed to investigate: (1) the ability of²⁰¹Tl SPECT to detect cardiac involvement of sarcoidosis with images recorded at rest and 2 hours later, and (2) the relationships between²⁰¹Tl myocardial SPECT findings and the activity of sarcoidosis or endomyocardial biopsy findings. As to the abnormal findings in²⁰¹Tl myocardial SPECT, (1) a low density area was seen in 13 of 41 cases (31.7%) and non-uniform uptake was found in 17 cases (41.5%), (2) the mean washout ratio (n=39) was 16.5±7.4%, which is significantly (p < 0.05) lower than that found in normal subjects, 23.9±7.5 % (n=10). Of the 19 patients judged visually to be normal, 5 patients had a reduced mean washout ratio less than 12%. Thus, the incidence of abnormal findings including all types of abnormality, on²⁰¹Tl myocardial SPECT in sarcoidosis was 63.4% (26/41 cases). In studying the relationship between²⁰¹Tl myocardial SPECT findings and the activity of sarcoidosis (as measured by the serum ACE (angiotensin converting enzyme) or lysozyme level, or the presence of more than 30% symphocyte fraction in BALF (broncho-alveolar lavage fluid)), 20 (80%) of 25 cases with²⁰¹Tl abnormality were judged to be active sarcoidosis, while only 6 (37.5%) of 16 cases with normal findings on²⁰¹Tl SPECT were judged to be active. This suggests that there is a significant (p < 0.01) relationship between the presence or absence of an abnormal finding on²⁰¹Tl myocardial SPECT and the activity of sarcoidosis. Among 13 patients examined by endomyocardial biopsy, 10 patients had abnormal findings on²⁰¹Tl myocardial SPECT and 7 of these 10 patients had no histological evidence of cardiac sarcoidosis. In all of these 7 patients, however, sarcoidosis was judged to be active. This suggest that endomyocardial biopsy is of limited value in the diagnosis of cardiac sarcoidosis.     

Regulation of pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells in endotoxin-enhanced reperfusion injury after total hepatic ischemia

The effects of Kupffer cells on cytokine responses in endotoxin-enhanced reperfusion injury after total hepatic ischemia were investigated in this study. Male rats pretreated with either normal saline solution (NS group) or gadolinium chloride (GdCl(3)) to inhibit Kupffer cell function (GC group) were subjected to 60 min of hepatic ischemia. These animals received either normal saline solution or sublethal doses of endotoxin (1 mg/kg) at reperfusion. In the NS group, endotoxin administration induced an enhanced tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 production 1 h after reperfusion with a subsequent peak of macrophage inflammatory protein-2 (MIP-2) levels, which resulted in a 7-day survival rate of 30%. Despite endotoxin administration, GdCl(3) pretreatment significantly suppressed TNF-alpha and increased interleukin-10 production 1 h after reperfusion, which led to a decline in MIP-2 production and amelioration of functional and structural liver damage with a 7-day survival rate of 80%. Augmented pro-inflammatory and anti-inflammatory cytokine responses by Kupffer cells were associated with endotoxin-enhanced reperfusion injury after hepatic ischemia. Kupffer cell blockade has a potential to attenuate the insult via modulation of cytokine responses.     

Development of a therapeutic adenoviral vector for cholangiocarcinoma combining tumor-restricted gene expression and infectivity enhancement

Cholangiocarcinoma is an invasive malignancy that is most often unresectable upon diagnosis and unresponsive to chemotherapy and radiation. While adenoviral gene therapy has shown promise in treating many tumors, systemic toxicity and low tumor transduction efficiency have hampered its application in many gastrointestinal cancers. To overcome these difficulties, we have constructed an adenoviral vector utilizing a tumor-specific promoter (TSP) for selective transgene expression and a vector with an RGD-motif in the fiber-knob region for infectivity enhancement. In seeking a TSP for cholangiocarcinoma, Secretory Leukoprotease Inhibitor, Midkine, Gastrin Releasing Peptide, VEGF, Cox-2M, and Cox-2L promoters were configures in adenoviral vectors, and evaluated in cholangiocarcinoma cells lines (Oz and SkChA-1). Luciferase assays demonstrated that Cox-2 promoters (M and L) showed the highest promoter activity, with Cox-2M appearing slightly stronger than Cox-2L. Infectivity enhanced vectors with RGD-motif in the fiber-knob region were also constructed with the luciferase transgene driven by a CMV control and the Cox-2M and Cox-2L promoters. Subsequent luciferase assays comparing the unmodified vectors to the RGD-modified versions demonstrated higher levels of luciferase activity than the RGD-infected cells. This paradigm was then applied to a therapeutic HSV-TK/GCV model by constructing RGD-enhanced HSV-TK vectors driven by Cox-2M and Cox-2L promoters. In vitro cytocidal effect analysis confirmed that the RGD-modified, cox-2 (M and L) driven vectors showed a stronger cytocidal effect upon gancyclovir administration than the vectors with wild-type fiber. The Cox-2 promoter demonstrates a favorable selectivity profile for cholangiocarcinoma, and RGD-modification further enhances transduction efficiency. This combination has potential to overcome the obstacles to clinical application of adenoviral gene therapy in cholangiocarcinoma. Presented at the Forty-Third Annual Meeting of The Society for Surgery of The Alimentary Tract, San Francisco, California, May 19–22, 2002 (oral presentation).     

Nodal status of malignant lymphoma in pelvic and retroperitoneal lymphatic pathways: comparison of integrated PET/CT with or without contrast enhancement

AIM: To determine the diagnostic accuracy of integrated contrast-enhanced positron emission tomography (PET) and computed tomography (CT), as compared with non-contrasted PET/CT, in evaluating nodal status of malignant lymphoma in pelvic and retroperitoneal lymphatic pathways. MATERIALS AND METHODS: Sixty-six patients (33 men and 33 women) with malignant lymphoma underwent staging with integrated CT and fluorine-18-fluorodeoxyglucose ((18)FDG) PET. Tumor types were diffuse large B-cell lymphoma (n=26, 39%), follicular lymphoma (n=20, 30%), Hodgkin disease (n=16, 24%), and marginal zone B-cell lymphoma (n=4, 6%). Both non-contrasted PET/CT and contrast-enhanced PET/CT images were examined separately by two different qualified physicians for each imaging modality, and nodal status of pelvic and retroperitoneal lymphatic pathways was evaluated. Reference standard included follow-up with clinical, laboratory, and conventional CT findings. We compared diagnostic accuracy retrospectively on basis of per-patient and per-lesion analyses between two modalities using McNemar test, respectively. RESULTS: Nodal status of pelvic and retroperitoneal lymphatic pathways was more accurately determined on contrast-enhanced PET/CT (n=52, 79%) compared with non-contrasted PET/CT (n=47, 71%). Difference in the accuracy of nodal staging between non-contrasted PET/CT and contrast-enhanced PET/CT was significant (p=0.048). On basis of per-lesion analysis, contrast-enhanced PET/CT determined more accurately the status of external iliac lymph node (p=0.002), internal iliac lymph node (p<0.0001), and common iliac lymph node (p=0.002) compared with non-contrasted PET/CT. Diagnostic accuracies of paraaortic lymph node, aortocaval lymph node, and paracaval lymph node were similar by either non-contrasted PET/CT or contrast-enhanced PET/CT. CONCLUSION: Integrated contrast-enhanced PET/CT improves the diagnostic accuracy in evaluating nodal status of pelvic and retroperitoneal lymphatic pathways in patients with malignant lymphoma.     

Computer-aided detection in computed tomography colonography: current status and problems with detection of early colorectal cancer

PURPOSE: The aim of this study was to evaluate the usefulness of computer-aided detection (CAD) in diagnosing early colorectal cancer using computed tomography colonography (CTC). MATERIALS AND METHODS: A total of 30 CTC data sets for 30 early colorectal cancers in 30 patients were retrospectively reviewed by three radiologists. After primary evaluation, a second reading was performed using CAD findings. The readers evaluated each colorectal segment for the presence or absence of colorectal cancer using five confidence rating levels. To compare the assessment results, the sensitivity and specificity with and without CAD were calculated on the basis of the confidence rating, and differences in these variables were analyzed by receiver operating characteristic (ROC) analysis. RESULTS: The average sensitivities for the detection without and with CAD for the three readers were 81.6% and 75.6%, respectively. Among the three readers, only one reader improved sensitivity with CAD compared to that without. CAD decreased specificity in all three readers. CAD detected 100% of protruding lesions but only 69.2% of flat lesions. On ROC analysis, the diagnostic performance of all three readers was decreased by use of CAD. CONCLUSION: Currently available CAD with CTC does not improve diagnostic performance for detecting early colorectal cancer. An improved CAD algorithm is required for detecting flat lesions and reducing the false-positive rate.     

Lymphoepithelial Cyst of the Pancreas: Report of a Case

A lymphoepithelial cyst (LEC) is an extremely rare benign lesion of the pancreas. During a medical check-up, a 77-year-old man without any symptoms was found to have a cyst in the body of the pancreas. His serum carbohydrate antigen 19-9 level was slightly elevated. Computed tomography showed a multilocular, low-attenuating cyst on the superior surface of the pancreatic body. Thus, we performed distal pancreatectomy with splenectomy. Histological examination revealed that the cyst wall was lined with squamous epithelium and surrounded by abundant mature lymphoid tissue. Keratinous substances were present in the cyst. An LEC of the pancreas is associated with a good prognosis and, although unusual, it should be considered in the differential diagnosis of pancreatic cystic lesions. Minimal resection of the cyst should be performed whenever possible, and extensive surgery avoided. For patients with a high surgical risk, fine-needle aspiration biopsy may be considered.