Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer - a retrospective comparative study with PET/CT and breast MRI.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden. METHODS: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance. RESULTS: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone. CONCLUSIONS: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Vertebral artery dissection stroke in evolution presented with postural headache as initial manifestation.

In young adult, the most common etiology of acute ischemic brain infarction are arterial dissections and cardiogenic embolic stroke. Vertebral artery dissection without preceding trauma history is quite rare in young ischemic stroke patients. Postural headache is even more atypical presentation for vertebral artery dissection. It is often misdiagnosed as spontaneous intracranial hypotension. We described a 37-year-old male suffering from acute onset postural headache with stroke in evolution during hospitalization. The initial brain magnetic resonance imaging (MRI) mislead to diagnosis of ischemic lesion. Nevertheless, with the aid of single photon emission computed tomography, we are confident the patient was afflicted with ischemic/hemorrhagic lesion, instead of neoplasm or demyelinating diseases. Lateral medullary syndrome was confirmed on the repeated brain MRI. His general condition improved with steady gait and clear articulation without easychoking after adequate hydration and rehabilitation training with aspirin as secondary prevention. Cranial artery dissections is a crucial differential diagnosis while thunderclap headache happens even related to postural change without obvious neurological deficit in the beginning presentations.

Comparative assessment of therapeutic safety of norcantharidin, N-farnesyloxy-norcantharimide, and N-farnesyl-norcantharimide against Jurkat T cells relative to human normal lymphoblast: A quantitative pilot study.

The therapeutic safety of an anticancer drug is one of the most important concerns of the physician treating the cancer patient. Half maximal inhibitory concentration (IC50) and hillslope are usually used to represent the strength and sensitivity of an anticancer drug on cancer cells. The therapeutic safety of the anticancer drug can be assessed by comparing the IC50 and hillslope of anticancer drugs on cancer cells relative to normal cells. Since there are situations where "more anticancer activity" implies "more toxicity," the safety of an anticancer drug in these situations is hard to evaluate by using IC50 and hillslope alone. In a previous study, the "net effect" index was devised to represent the net therapeutic effects of one anticancer drug relative to the other. However, the therapeutic safety of one specific anticancer drug alone was not defined in the "net effect" index. This study introduced the "safety index (SI)" to quantify the degree of safety of an anticancer drug by using 4-parameter logistic model on cancer cells relative to normal cells. The therapeutic safety of norcantharidin (NCTD), N-farnesyloxy-norcantharimide (NOC15), and N-farnesyl-norcantharimide (NC15) in the treatment of Jurkat T cells relative to human normal lymphoblast was compared using the newly defined SI. We found that the SI of NOC15 and NC15 was significantly higher than that of NCTD, suggesting that both NOC15 and NC15 can damage more cancer cells and less normal cells than NCTD. We conclude that both NOC15 and NC15 are safer anticancer drugs than NCTD in the treatment of Jurkat T cells relative to human normal lymphoblast. The SI can be further applied to the screening, developments, and applications of anticancer drugs in the future.

Tc-99m imaging in thyroidectomized differentiated thyroid cancer patients immediately before I-131 treatment.

PURPOSE: The aim of this study was to evaluate the clinical role of technetium-99m pertechnetate (Tc-99m) imaging in thyroidectomized differentiated thyroid cancer patients immediately before radioiodine-131 (I-131) treatment (Tx). PATIENT AND METHODS: Eighty-six consecutive post-total-thyroidectomy patients (15 men, 71 women; mean age: 46.8 years) with pathologically diagnosed differentiated thyroid cancer were retrospectively studied. Tc-99m imaging immediately before I-131 Tx using both patient-based and lesion-based measurements were analyzed and were further compared with those of post-Tx I-131 whole-body scans. RESULTS: For patients with unequivocally positive Tc-99m uptake, the sensitivity was 77% (patient-based) and 59% (site-based). The positive predictive value (PPV) was 100% for both patient-based and site-based measurements. If equivocal Tc-99m uptake was counted as positive, the sensitivity was 83 and 67%, and the PPV was 100 and 99% for patient-based and site-based measurements, respectively. CONCLUSION: (a) To increase sensitivity yet maintaining high PPV, equivocal Tc-99m uptake should be considered a positive finding. (b) The nearly 100% PPV of Tc-99m imaging immediately before I-131 Tx for remnant detection suggests that Tc-99m imaging not only serves as an alternative to low-dose I-131 scanning in the low-risk post-thyroidectomy patients but also provides a clue for the subsequent I-131 therapeutic dosage and even for the outcome prediction.

N-Farnesyloxy-norcantharimide inhibits progression of human leukemic Jurkat T cells through regulation of mitogen-activated protein kinase and interleukin-2 production.

This study investigated the anticancer effects of N-farnesyloxy-norcantharimide (NOC15), a newly synthesized norcantharidin (NCTD) analogue, on human leukemic Jurkat T cells and the signaling pathway underlying its effects. We found that the half maximal inhibitory concentration (IC50) of NOC15 on Jurkat T cells is 1.4 µmol/l, which is 11.14-fold (=15.6÷1.4) smaller than the 15.6 µmol/l of NCTD on Jurkat T cells, whereas the IC50 of NOC15 on human normal lymphoblast (HNL) is 207.9 µmol/l, which is 8.17-fold (=1698.0÷207.8) smaller than the 1698.0 µmol/l of NCTD on HNL cells. These results indicated that NOC15 exerts a higher anticancer effect on Jurkat T cells and has higher toxicity toward HNL cells than NCTD. Thus, NOC15 is 1.36-fold (=11.14÷8.17) beneficial as an anticancer agent toward Jurkat T cells compared with NCTD. Moreover, NOC15 can increase the percentage of cells in the sub-G1 phase and reduce the cell viability of Jurkat T cells, stimulate p38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) of mitogen-activated protein kinases (MAPKs) signaling pathway, and inhibit calcineurin expression and interleukin-2 (IL-2) production. However, NOC15 exerted no effects on the Jun-N-terminal kinase 1/2 (JNK1/2) signaling pathway, the production of IL-8, and tumor necrosis factor-α. We conclude that the anticancer activity of the newly synthesized NOC15 is 1.36-fold beneficial than NCTD as an anticancer agent and that NOC15 can increase the percentage of cells in the sub-G1 phase through the stimulation of p38 and ERK1/2 of the MAPK signaling pathway and the inhibition of calcineurin expression and IL-2 production. The NOC15 may have the potential of being developed into an anticancer agent in the future.

N-Farnesyloxy-norcantharimide and N-farnesyl-norcantharimide inhibit the progression of leukemia and increase survival days in a syngeneic mouse leukemia model.

This study investigated the anticancer effects of two newly synthesized norcantharidin analogs, N-farnesyloxy-norcantharimide (NOC15) and N-farnesyl-norcantharimide (NC15), in L1210 cells and in a syngeneic mouse leukemia model (L1210 cell line plus DBA/2 mice). We found that the half-maximal inhibitory concentration (IC50) of NOC15 and NC15 on L1210 cells is 1.56 and 2.62 µmol/l, respectively, and that the IC50 of NOC15 and NC15 on human normal lymphoblast is 207.9 and 2569 µmol/l, respectively. In cell cycle analysis, NOC15 could increase the sub-G1 phase, whereas NC15 could induce G2/M arrest. Annexin-V apoptosis assay indicated that both NOC15 and NC15 could induce cell apoptosis. In the syngeneic mouse leukemia model, both NOC15 and NC15 could increase the survival days of mice and decrease the tumor weight. Moreover, both NOC15 and NC15 could retard the increase in peripheral blood leukocyte count due to L1210 cells. In the subcutaneous (s.c.) group, the treatment with NOC15 could retard the decrease in the weight of the liver and the spleen caused by L1210 cells, whereas the treatment with NC15 could retard the decrease in the weight of the spleen caused by L1210 cells. We conclude that the new compounds NOC15 and NC15 have strong anticancer activity and low toxicity both in vitro and in vivo. NOC15 and NC15 may have the potential to be developed into anticancer agents in the future.

PET or PET/CT for detection of peritoneal carcinomatosis: a meta-analysis.

UNLABELLED: The present study assessed the diagnostic performances of (18)F-FDG PET or PET/CT in detecting peritoneal carcinomatosis in patients with cancer. METHODS: Through a search of MEDLINE (January 1998 to September 2012), an overall weighted average for sensitivity and specificity was calculated using the weighted averages of the sample sizes in each relevant study. Pooled estimates of positive and negative likelihood ratios were calculated using fixed and random effects models, respectively, according to the heterogeneity among studies. A summary receiver operating characteristics (sROC) curve was constructed and the area under the sROC curve (AUC) was calculated. To explore heterogeneity, due to sources other than threshold effects, I-square was calculated. RESULTS: The present study included analyses of patients (n = 513) from 7 studies. Results indicated a significant heterogeneity for sensitivity and specificity (I(2) > 50% and P < 0.05). The overall pooled estimates for sensitivity and specificity of FDG PET or PET/CT scans in the detection of peritoneal carcinomatosis were 72.4% (95% CI, 64.4%-79.5%) and 96.7% (95% CI, 94.4%-98.3%), respectively. The positive likelihood ratio was 10.414 (95% CI, 6.195-17.506) and the negative likelihood ratio 0.312 (95% CI, 0.159-0.612). The AUC was 0.9404. The overall diagnostic accuracy (Q* index) was 87.8%. CONCLUSION: The high specificity may provide the reliability of a positive FDG PET or PET/CT to detect peritoneal carcinomatosis in patients with cancer. FDG PET or PET/CT has only weak power to exclude the presence of peritoneal carcinomatosis. By a good overall diagnostic accuracy, FDG PET or PET/CT may prove beneficial to surgeons when selecting appropriate patients on whom to perform laparoscopy or laparotomy.

Accuracy of whole-body FDG-PET and FDG-PET/CT in M staging of nasopharyngeal carcinoma: a systematic review and meta-analysis.

BACKGROUND: A meta-analysis was conducted to evaluate the accuracy of whole-body positron emission tomography (PET) or PET/CT in M staging of nasopharyngeal carcinoma (NPC). METHODS: Through a search of relevant English language studies from October 1996 to September 2011, pooled estimated sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and summary receiver operating characteristic (SROC) curves of whole-body PET or PET/CT in M staging of NPC were calculated. RESULTS: Three PET and 5 PET/CT studies were identified. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of FDG-PET or PET/CT were 0.83 (95% confidence interval [CI], 0.77-0.88), 0.97 (95% CI, 0.95-0.98), 23.38 (95% CI, 16.22-33.69), and 0.19 (95% CI, 0.13-0.25), respectively. The area under curve was 0.9764 and Q* index estimate was 0.9307 for FDG-PET or PET/CT. CONCLUSION: Current evidence confirms the good diagnostic performance of the whole-body FDG-PET or PET/CT in M staging of NPC.

18F-FDG PET or PET/CT for detection of metastatic lymph nodes in patients with endometrial cancer: a systematic review and meta-analysis.

UNLABELLED: The present study assessed the diagnostic performances of 18F-FDG PET or PET/CT in detecting pelvic and/or paraaortic lymph node metastasis in patients with endometrial cancer. METHODS: Through a search of MEDLINE (January 1998 to March 2011), an overall weighted average for sensitivity and specificity as well as pooled estimates of positive and negative likelihood ratios were calculated. A summary receiver-operating-characteristics (sROC) curve was constructed and the area under the sROC curve (AUC) was calculated. I-square was calculated to explore heterogeneity. RESULTS: The present study included 243 patients from seven studies. Results indicated a lack of significant heterogeneity for sensitivity and specificity (I2<50% and p>0.05). The overall pooled estimates for sensitivity and specificity of FDG-PET or PET/CT scans in the detection of pelvic and/or paraaortic metastasis were 63.0% (95% CI, 48.7-75.7%) and 94.7% (95% CI, 90.4-97.4%), respectively. The positive likelihood ratio was 10.465 (95% CI, 5.646-19.396) and the negative likelihood ratio 0.399 (95% CI, 0.284-0.560). The AUC was 0.9533. The overall diagnostic accuracy (Q* index) was 89.5%. Conclusion The high positive likelihood value confirms the reliability of a positive FDG-PET or PET/CT to detect pelvic and/or paraaortic lymph nodes metastasis in patients with untreated endometrial cancer. FDG-PET or PET/CT may prove beneficial to surgeons when selecting appropriate patients on whom to perform lymphadenectomy.

Meta-analysis: comparison of F-18 fluorodeoxyglucose-positron emission tomography and bone scintigraphy in the detection of bone metastasis in patients with lung cancer.

RATIONALE AND OBJECTIVES: The aim of this review was to evaluate the diagnostic properties of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) or PET/computed tomography (CT) and bone scintigraphy in the detection of osseous metastases in patients with lung cancer. MATERIALS AND METHODS: MEDLINE was searched for relevant original articles published between January 1995 and August 2010. Inclusion criteria were as follows: FDG-PET or PET/CT and bone scintigraphy was carried out to detect bone metastases in patients with lung cancer, sufficient data were presented to construct a 2 × 2 contingency table, and histopathologic analysis and/or close clinical and imaging follow-up and/or radiographic confirmation by multiple imaging modalities was used as the reference standard. Two reviewers independently extracted data related to research design, sample size, imaging techniques, technical characteristics, reference standards, methods of imaging interpretation, and totals of true-positives, false-positives, true-negatives, and false-negatives. Stata was used to obtain per patient and per lesion pooled estimates of sensitivity, specificity, and positive and negative likelihood ratios, and areas under summary receiver-operating characteristic curves (AUCs) were calculated. RESULTS: The pooled patient-based sensitivity of FDG-PET or PET/CT was 0.93 (95% confidence interval [CI], 0.88-0.96), specificity was 0.95 (95% CI, 0.91-0.98), and the AUC was 0.94. The pooled sensitivity of bone scans was 0.87 (95% CI, 0.79-0.93), specificity was 0.82 (95% CI, 0.62-0.92), and the AUC was 0.91. The pooled lesion-based sensitivity of FDG-PET or PET/CT was 0.93 (95% CI, 0.84-0.97), specificity was 0.91 (95% CI, 0.80-0.96), and the AUC was 0.97. The pooled sensitivity of bone scans was 0.92 (95% CI, 0.87-0.95), specificity was 0.57 (95% CI, 0.09-0.95), and the AUC was 0.92. CONCLUSIONS: Although FDG-PET or PET/CT has higher sensitivity and specificity than bone scintigraphy, further research with a less biased design is needed to determine the most efficacious imaging modality for the detection of metastatic lung cancer.

Value of gallium-67 scanning in monitoring therapeutic effectiveness in a patient with relapsing polychondritis.

We present a 57-year-old man who had low-grade fever and painful, swollen and erythematous ears. Gallium-67 citrate scintigraphy (gallium scan) performed prior to the commencement of treatment showed increased gallium uptake in bilateral external ears, neck, mediastinum and bilateral pulmonary hili. The results of ultrasonography of both ears were compatible with the diagnosis of chondritis. The patient's clinical condition and laboratory data improved after a course of nonsteroidal anti-inflammatory drugs and steroids. Gallium scan performed after treatment showed a diminished uptake in the external ears, neck, and mediastinum. Gallium scintigraphy is a valuable tool for evaluating inflammatory activity and monitoring therapeutic response in patients with relapsing polychondritis.

Dual-phase 99mTc-MIBI parathyroid imaging reveals synchronous parathyroid adenoma and papillary thyroid carcinoma: a case report.

The possibility of a coincidental appearance of hyperparathyroidism and thyroid cancer is not often considered because of its low incidence. Here, we present a case of a 49-year-old woman with a parathyroid adenoma coexisting with two sites of papillary thyroid carcinoma. Dual-phase 99mTc-methoxyisobutylisonitrile (MIBI) parathyroid imaging before the operation correctly visualized the site of the parathyroid adenoma. In addition, two papillary thyroid carcinomas showed faint uptake of 99mTc-MIBI on delayed image. Total thyroidectomy and parathyroidectomy of a solitary parathyroid adenoma were performed. The patient subsequently underwent radioiodine-131 ablation and was treated with T4 suppression. This case illustrates the need for clinical awareness of concomitant hyperparathyroidism and thyroid cancer. Dual-phase 99mTc- MIBI parathyroid imaging may be useful for detecting indolent thyroid cancer before it becomes a distinct disease.