Instability of the first metatarsal-cuneiform joint: diagnosis and discussion of an independent pain generator in the foot.

BACKGROUND: First metatarsocuneiform (MC) instability is recognized as a pathologic contributor to hallux valgus. There are no studies identifying the first MC joint as an independent pain generator in the foot that may require surgical arthrodesis for its management. MATERIALS AND METHODS: The authors reviewed the records of all patients with this newly described pathology in the first MC joint. There were 61 patients with 85 feet who underwent a fluoroscopically guided local anesthetic injection into the first metatarsocuneiform joint to assess pain relief. Patient's complaints, physical exam findings, treatment decisions, patient characteristics, and radiographic findings were evaluated. RESULTS: Seventy-nine percent of patients (67/85) injected had relief of their symptoms. Eight or these 67 patients were eventually treated with first MC arthrodesis with complete relief of symptoms. The average time from onset of symptoms to presentation was 21 (range, 1 to 72) months. Eighty-five percent of feet (72/85) had multiple previous diagnoses. Radiographic plantar widening of the first M-C joint on weightbearing views was inconsistent with pathology. CONCLUSION: The first MC joint is an independent pain generator in the foot that can have variable presentations. Radiographic data can often be helpful, but clinical exam findings are paramount in the diagnosis. Fluoroscopically-guided long acting local anesthetic injections of this joint are helpful in the diagnosis, especially in the patient with multiple possible pain generators in the foot and ankle. Failure to recognize the first MC joint as a source of pain may lead to delay in treatment, misdiagnosis, and mistreatment of foot pathology.

Comparison of MRI and local anesthetic tendon sheath injection in the diagnosis of posterior tibial tendon tenosynovitis.

BACKGROUND: The modalities currently available to clinicians to confirm the clinical suspicion of posterior tibial tendinitis include MRI, CT, sonography, tenography, and local anesthetic tendon sheath injections. There are no reports in the literature comparing local anesthetic tendon sheath injection to MRI as tools for diagnosing posterior tibial tenosynovitis. METHODS: The authors reviewed the records of all patients with stage 1 posterior tibial tendon dysfunction between the dates of September 1, 2001, to November 21, 2004. Fifteen patients (17 ankles) had a local anesthetic injection into the posterior tibial tendon sheath and MRI for clinically suspected tenosynovitis of the posterior tibial tendon. RESULTS: Seventeen (100%) of 17 ankles had complete relief of symptoms after the local anesthetic tendon sheath injections. Fifteen (88%) of 17 ankles had abnormally increased fluid signal within the posterior tibial tendon sheath seen on MRI. Two of two ankles (100%), after having negative MRI findings, had complete relief with a local anesthetic tendon sheath injection. In addition, conservative treatment failed in these two patients, and they subsequently had tenosynovectomy with gross confirmation at surgery of inflammatory changes within the tendon sheath. These two patients had complete symptom relief after tenosynovectomy. CONCLUSIONS: Local tendon sheath injections and MRI are both reliable diagnostic tools. Injection of the posterior tibial tendon is an accurate, safe, and sensitive modality useful in patients in whom MRI studies are negative in the face of continued clinical suspicion.

Quantitative tumor apoptosis imaging using technetium-99m-HYNIC annexin V single photon emission computed tomography.

PURPOSE: Radiolabeled annexin V may allow for repetitive and selective in vivo identification of apoptotic cell death without the need for invasive biopsy. This study reports on the relationship between quantitative technetium-99m- (99mTc-) 6-hydrazinonicotinic (HYNIC) radiolabeled annexin V tumor uptake, and the number of tumor apoptotic cells derived from histologic analysis. PATIENTS AND METHODS: Twenty patients (18 men, two women) suspected of primary (n = 19) or recurrent (n = 1) head and neck carcinoma were included. All patients underwent a spiral computed tomography (CT) scan, 99mTc-HYNIC annexin V tomography, and subsequent surgical resection of the suspected primary or recurrent tumor. Quantitative 99mTc-HYNIC annexin V uptake in tumor lesions divided by the tumor volume, derived from CT, was related to the number of apoptotic cells per tumor high-power field derived from terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assays performed on sectioned tumor slices. RESULTS: Diagnosis was primary head and neck tumor in 18 patients, lymph node involvement of a cancer of unknown primary origin in one patient, and the absence of recurrence in one patient. Mean percentage absolute tumor uptake of the injected dose per cubic centimeter tumor volume derived from tomographic images was 0.0003% (standard deviation [SD], 0.0004%) at 1 hour postinjection (PI) and 0.0001% (SD, 0.0000%) at 5 to 6 hours PI (P =.012). Quantitative 99mTc-HYNIC annexin V tumor uptake correlated well with the number of apoptotic cells if only tumor samples with no or minimal amounts of necrosis were considered. CONCLUSION: In the absence of necrosis, absolute 99mTc-HYNIC annexin V tumor uptake values correlate well with the number of apoptotic cells derived from TUNEL assays.

Safety, biodistribution, and dosimetry of 99mTc-HYNIC-annexin V, a novel human recombinant annexin V for human application.

UNLABELLED: 99mTc-hydrazinonicotinamido (HYNIC)-annexin V is a novel tracer for in vivo imaging of apoptosis. The present study on humans was performed to investigate the safety of (99m)Tc-HYNIC-annexin V and to quantify the biodistribution and radiation dose. METHODS: Six healthy, male volunteers participated in the study. A dual-head gamma camera was used to acquire conjugate anterior and posterior views. Imaging started with a transmission scan using a (57)Co-flood source to obtain a map of the local thickness of the volunteer. Approximately 250 MBq of (99m)Tc-HYNIC-annexin V were injected intravenously, directly followed by a 30-min dynamic study. Whole-body scans were obtained at about 30 min, 3 h, 6 h, and 24 h after injection. Organ uptake was determined after correction for background, scatter, and attenuation. The MIRDOSE3.1 program was used to calculate organ-absorbed doses and effective dose. Signs of adverse effects were investigated by monitoring renal and liver function, hematology, blood coagulation, and vital signs (blood pressure, pulse, respiration rate, temperature, and electrocardiogram). RESULTS: The kidneys accumulated 49.7 +/- 8.1 percentage injected dose (%ID) at 3 h after injection; the liver, 13.1 +/- 1.0 %ID; the red marrow, 9.2 +/- 1.8 %ID; and the spleen, 4.6 +/- 1.6 %ID. More than 90% of the blood activity was cleared with a half-life of 24 +/- 3 min. The biologic half-life of the activity registered over the total body was long (69 +/- 7 h). Excretion of the activity was almost exclusively through the urine (22.5 +/- 3.5 %ID at 24 h), and hardly any activity was seen in the bowel or feces. Absorbed doses were found to be 196 +/- 31 micro Gy/MBq for the kidneys, 41 +/- 12 micro Gy/MBq for the spleen, 16.9 +/- 1.3 micro Gy/MBq for the liver, and 8.4 +/- 0.9 micro Gy/MBq for the red marrow. The effective dose was 11.0 +/- 0.8 micro Sv/MBq, or 2.8 +/- 0.2 mSv for the average injected activity of 250 MBq. No adverse effects were observed. CONCLUSION: (99m)Tc-HYNIC-annexin V is a safe radiopharmaceutical, having a favorable biodistribution for imaging of apoptosis in the abdominal as well as thoracic area with an acceptable radiation dose.

Monitoring apoptosis in real time.

Many therapeutically active anticancer treatments exert their effect by the induction of apoptosis and necrosis. Serial biopsies in breast cancer patients have suggested that response to therapy correlates with early posttreatment increases in tumor apoptotic index. Radiolabeled technetium Tc 99m-recombinant human (rh) annexin V provides a noninvasive technique for imaging treatment-induced cell death. Annexin V is a naturally occurring human protein that binds avidly to membrane-associated phosphatidylserine (PS). PS is normally found only on the inner leaflet of the cell membrane double layer, but it is actively transported to the outer layer as an early event in apoptosis and becomes available for annexin binding. Annexin also gains access to PS as a result of the membrane fragmentation associated with necrosis. In vitro studies of apoptosis using fluorescein annexin have shown good correlation with assessments of apoptosis documented by nuclear DNA degradation and caspase activation. In vivo localization of intravenously administered Tc 99m-annexin V has been demonstrated in numerous preclinical models of apoptosis, including anti-Fas-mediated hepatic apoptosis, rejection of allogeneic heterotopic cardiac allografts, cyclophosphamide treatment of murine lymphoma, cyclophosphamide-induced apoptosis in bone marrow, and leukocyte apoptosis associated with abscess formation. Scintigraphic studies in humans using Tc 99m-rh annexin V have demonstrated the feasibility of imaging cell death in acute myocardial infarction, in tumors with a high apoptotic index, and in response to anti-tumor chemotherapy of non-small cell lung cancer, small-cell lung cancer, breast cancer, lymphoma, and sarcoma. Increased localization of Tc 99m-rh annexin V within 1 to 3 days of chemotherapy has been noted in some, but not all, subjects with these tumors. To date, most subjects showing increased Tc 99m-rh annexin V uptake after the first course of chemotherapy have shown objective clinical responses. A single site study in 15 subjects with 1-year follow-up has suggested that increased posttreatment Tc 99m-rh annexin uptake is associated with improved time to progression of disease and survival time. In vivo imaging of cell death may have the potential to improve the treatment of cancer patients by allowing rapid, objective, patient-by-patient assessment of the efficacy of tumor cell killing.