Neoadjuvant 177Lu-PSMA-I&T Radionuclide Treatment in Patients with High-risk Prostate Cancer Before Radical Prostatectomy: A Single-arm Phase 1 Trial.

BACKGROUND: High-risk localized prostate cancer (HRLPC) has a substantial risk of disease progression despite local treatment. Neoadjuvant systemic therapy before definitive local therapy may improve oncological outcomes by targeting the primary tumor and micrometastatic disease. OBJECTIVE: To evaluate whether a lutetium-177 prostate-specific membrane antigen radioligand (LuPSMA) can be safely administered to patients with HRLPC before robot-assisted radical prostatectomy (RARP) and to describe immediate oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was an open-label, single-arm clinical trial. Patients with HRLPC and elevated radioligand uptake on PSMA positron emission tomography/computed tomography were enrolled. Two or three LuPSMA radioligand doses (7.4 GBq) were given at 2-wk intervals. RARP with lymph node dissection was performed 4 wk after the last LuPSMA dose. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The rate of surgical complications, operative parameters, changes in functional and quality-of-life measures, and immediate oncological outcomes (histological findings and biochemical response) were measured. Data were analyzed descriptively. RESULTS AND LIMITATIONS: Fourteen patients participated (median age 67 yr). Prostate-specific antigen decreased by 17% (interquartile range [IQR] 9-50%) after two LuPSMA doses and 34% (IQR 11-60%) after three doses. Thirteen patients underwent RARP with no identifiable anatomical changes or intraoperative complications. Four patients (30%) had postoperative complications (pneumonia, pulmonary embolism, urinary leak with urinary tract infection). At 3 mo postoperatively, 12 patients (92%) required one pad or less. Final whole-mount pathology showed positive surgical margins (PSMs) in seven patients (53%) and downgrading to International Society of Urological Pathology grade group 3 in three patients (23%). Treatment-related effects included a clear vacuolated cytoplasm and pyknotic nuclei. CONCLUSIONS: LuPSMA followed by RARP appears to be surgically safe. While oncological outcomes are pending, continence recovery seems to be unaffected by LuPSMA treatment. PATIENT SUMMARY: We evaluated outcomes for patients with aggressive localized prostate cancer who received treatment with a radioactive agent before surgical removal of their prostate. This approach appears to be safe and feasible, but its therapeutic efficacy is still unknown.

Unilateral lower limb rest tremor is not necessarily a presenting symptom of Parkinson's disease.

Lower leg rest tremor is an uncommon symptom of neurological disease. Review of the files of 16 patients who presented with lower leg tremor (average age 58 +/- 16 years; average disease duration 6.8 +/- 8.5 years) yielded a diagnosis of Parkinson's disease (PD) in 5 and probable multiple system atrophy (MSA) in 3. In 4 patients with an indeterminate diagnosis, cardiac MIBG SPECT was positive in 3, indicating PD, and negative in one, suggesting MSA. Two patients each had psychogenic tremor and drug-induced parkinsonism. Although lower leg tremor is considered an unusual presentation of PD, it should raise suspicions of MSA and other neurodegenerative disorders.

Short- and long-term outcome of lung volume reduction surgery. The predictive value of the preoperative clinical status and lung scintigraphy.

The NETT study assessed the benefits of lung volume reduction surgery (LVRS) versus medical treatment. However, data is available only on the early outcome of LVRS (24 months). We evaluate the factors affecting the outcome at one-year and up to 6 years after LVRS. Thirty-seven patients underwent LVRS. Thirty-five patients, who survived the operation for at least one-year, were followed up to 6 years. Patients' laboratory, clinical and scintigraphic data before surgery were reviewed retrospectively, and follow-up at one-year and at the end of data collection. Successful LVRS with improvement of FEV(1)30% at one-year was observed in 13 of 35 patients. Five of these patients had initial FEV(1) values of <20% of the predicted. The group of patients with improvement was younger as compared to the 22 patients without improvement (P<0.005). The younger age group used less supplemental oxygen and had a PDiff of >23%. Combinations of age under 60 years and PDiff >23% were a favorable factor (P<0.002) for successful LVRS. Thirty-four patients were followed up to 6 years. Fifteen of the 34 patients (44.1%) remained well. Use of supplemental oxygen before surgery, and FEV(1) improvement of 30% at one-year after surgery were good prognostic factors. We concluded that the long-term success of LVRS is affected by non-dependence on oxygen supplementation before surgery, and the one-year post-surgical improvement of FEV(1) (30%). Based on our findings, the subgroup of patients below 60 years old with severe disease (FEV(1)<20%) and heterogeneous upper lobe emphysema (Pdiff>23%) has improved outcome.

Lymphatic drainage to the popliteal basin in distal lower extremity malignant melanoma.

UNLABELLED: Hypotheses Melanoma of the distal lower extremity may drain to the popliteal basin. Drainage pathways and retrieval of the popliteal sentinel nodes may affect patient outcome. DESIGN: Retrospective analysis of popliteal involvement in patients with stage IB or higher melanoma, operated on from August 1, 1993, to July 31, 2003. SETTING: Tertiary referral, university-affiliated medical center. PATIENTS: One hundred six melanoma patients who underwent combined lymphoscintigraphy and blue dye-guided sentinel node biopsy, radical popliteal dissection, or both. MAIN OUTCOME MEASURES: Incidence and patterns of drainage to popliteal nodes; effect on staging and outcome. RESULTS: Lymphoscintigraphy (n = 8) and physical examination (n = 2) identified 10 cases (9%) of draining to the popliteal basin, with concurrent drainage to the groin. Three distinct drainage patterns were identified, with different popliteal node locations. Seven of 8 popliteal sentinel nodes were retrieved, 1 of which was metastatic with no groin metastasis. Two patients had synchronous palpable popliteal and groin metastases and underwent radical groin and popliteal dissection. All 3 patients with popliteal metastases relapsed early with synchronous systemic and in-transit disease. One of 7 patients with negative sentinel nodes is alive with in-transit disease; all others are disease free. CONCLUSIONS: According to this series, the popliteal basin is the site of first drainage in about 9% of patients, with concurrent drainage to the groin. The 3 distinct patterns of drainage to the popliteal region and the presence of isolated popliteal metastases may affect the surgical treatment. Therefore, drainage to popliteal sentinel nodes and the pattern of this drainage should be noted in all distal lower extremity melanomas.

Non-resectable slow-growing meningiomas treated by hydroxyurea.

PURPOSE: To test the benefit of hydroxyurea in the treatment of recurrent and non-resectable slow-growing meningiomas. METHODS: Twelve patients with regrowing non-malignant meningiomas, were enrolled for a protocol of 2 years with continuous chemotherapy with hydroxyurea, 20 mg/kg/day. Response to treatment was evaluated both clinically and by diagnostic imaging using computed tomography (CT) and 201-Thallium single photon emission CT. One minimal response was documented by CT, accompanied by clinical stabilization. Nine patients showed progressive disease, at least by one imaging procedure, with a median time to progression of 13 months (range 4-24). Two other patients were not available for response due to early removal from the study, following abrupt manifestation of grades 3-4 hematological toxicity. CONCLUSION: In this series hydroxyurea has not shown effectiveness in the treatment of non-resectable slow-growing meningiomas: neither for achieving response, nor for arresting disease progression.

Patterns of papillary muscle ischemia in myocardial PET.

PURPOSE: Conventional nuclear medicine equipment lacks sufficient spatial resolution to reliably visualize the papillary muscles (PM). Positron emission tomography (PET), however, can adequately visualize these structures using various positron emitters. METHODS AND PATIENTS: We present various patterns of PM observed on myocardial PET imaging in 4 patients. These patterns demonstrate different pathologic conditions such as PM ischemia of varying severity, as well as hibernation, using both N-13 NH3 and F-18 FDG as perfusion and metabolic agents, respectively. These patterns of infarction, stress-induced myocardial ischemia, or hibernation can be identified in one or both PM using PET scanning. Normal PM visualization on chest F-18 FDG PET images is also presented. CONCLUSION: This report illustrates the potential ability of myocardial PET as a noninvasive modality to study the perfusion and metabolic abnormalities of the PM.