Altered drainage patterns in patients with melanoma and previous axillary dissection.

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously dissected axilla. Sentinel lymph node mapping is still an important adjunct in patients with melanoma despite previous axillary dissection

90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

AbstractBackgroundFor patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.MethodsFifty-eight patients with three (2–7) median prior treatments were treated on Arm A (N=29, 90Y-clivatuzumab tetraxetan, weekly 6.5mCi/m2doses×3, plus gemcitabine, weekly 200mg/m2 doses×4 starting 1week earlier) or Arm B (N=29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5mCi/m2doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.ResultsCytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3–9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan–Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29–0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1year.ConclusionsClinical studies of 90Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting

US-triggered Microbubble Destruction for Augmenting Hepatocellular Carcinoma Response to Transarterial Radioembolization: A Randomized Pilot Clinical Trial.

Combined US-triggered microbubble destruction and hepatocellular carcinoma radioembolization showed improved treatment response compared with radioembolization alone and no changes in vital signs or liver function. Background US contrast agents are gas-filled microbubbles (MBs) that can be locally destroyed by using external US. Among other bioeffects, US-triggered MB destruction, also known as UTMD, has been shown to sensitize solid tumors to radiation in preclinical models through localized insult to the vascular endothelial cells. Purpose: To evaluate the safety and preliminary efficacy of combining US-triggered MB destruction and transarterial radioembolization (TARE) in participants with hepatocellular carcinoma (HCC). Materials and Methods: In this pilot clinical trial, participants with HCC scheduled for sublobar TARE were randomized to undergo either TARE or TARE with US-triggered MB destruction 1–4 hours and approximately 1 and 2 weeks after TARE. Enrollment took place between July 2017 and February 2020. Safety of US-triggered MB destruction was evaluated by physiologic monitoring, changes in liver function tests, adverse events, and radiopharmaceutical distribution. Treatment efficacy was evaluated by using modified Response Evaluation Criteria in Solid Tumors (mRECIST) on cross-sectional images, time to required next treatment, transplant rates, and overall survival. Differences across mRECIST reads were compared by using a Mann-Whitney U test, and the difference in prevalence of tumor response was evaluated by Fisher exact test, whereas differences in time to required next treatment and overall survival curves were compared by using a log-rank (Mantel-Cox) test. Results: Safety results from 28 participants (mean age, 70 years ± 10 [standard deviation]; 17 men) demonstrated no significant changes in temperature (P = .31), heart rate (P = .92), diastolic pressure (P = .31), or systolic pressure (P = .06) before and after US-triggered MB destruction. No changes in liver function tests between treatment arms were observed 1 month after TARE (P \u3e .15). Preliminary efficacy results showed a greater prevalence of tumor response (14 of 15 [93%; 95% CI: 68, 100] vs five of 10 [50%; 95% CI: 19, 81]; P = .02) in participants who underwent both US-triggered MB destruction and TARE (P = .02). Conclusion: The combination of US-triggered microbubble destruction and transarterial radioembolization is feasible with an excellent safety profile in this patient population and appears to result in improved hepatocellular carcinoma treatment response

N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson\u27s Disease: Preliminary Clinical and Cell Line Data.

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson\u27s disease (PD). METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult with the neurotoxin rotenone. In the clinical study, patients continued their standard of care and were randomized to receive either daily NAC or were a waitlist control. Patients were evaluated before and after 3 months of receiving the NAC with DaTscan to measure dopamine transporter (DAT) binding and the Unified Parkinson\u27s Disease Rating Scale (UPDRS) to measure clinical symptoms. RESULTS: The cell line study showed that NAC exposure resulted in significantly more mDA neurons surviving after exposure to rotenone compared to no NAC, consistent with the protective effects of NAC previously observed. The clinical study showed significantly increased DAT binding in the caudate and putamen (mean increase ranging from 4.4% to 7.8%; p CONCLUSIONS: The results of this preliminary study demonstrate for the first time a potential direct effect of NAC on the dopamine system in PD patients, and this observation may be associated with positive clinical effects. A large-scale clinical trial to test the therapeutic efficacy of NAC in this population and to better elucidate the mechanism of action is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT02445651

Rosuvastatin alone or with extended-releasen niacin: a new therapeutic option for patients with combined hyperlipidemia

Combination therapy with a statin and niacin may provide optimal therapy for patients with combined hyperlipidemia and low levels of high-density lipoprotein (HDL) cholesterol. The authors assessed the efficacy and safety of rosuvastatin monotherapy, extended-release (ER) niacin monotherapy, or rosuvastatin and ER niacin combined therapy in patients with atherogenic dyslipidemia. In a 24-week, open-label, multicenter trial, men and women aged ?18 years with fasting levels of total cholesterol ?200 mg/dL, HDL cholesterol ?45 mg/dL, triglycerides 200-800 mg/dL, and apolipoprotein B ?110 mg/dL were randomly assigned to one of four treatment groups: rosuvastatin 10-40 mg, ER niacin 0.5-2 g, rosuvastatin 40 mg plus ER niacin 0.5-1 g, or rosuvastatin 10 mg plus ER niacin 0.5-2 g. Daily doses of rosuvastatin 40 mg monotherapy reduced low-density lipoprotein (LDL) cholesterol and non-HDL cholesterol levels significantly more than did either ER niacin 2 g monotherapy or rosuvastatin 10 mg combined with ER niacin 2 g. Addition of ER niacin 1 g to rosuvastatin 40 mg did not further reduce total or non-HDL cholesterol. Triglyceride reductions were similar among the four treatment groups. ER niacin mono- and combined therapy produced significantly greater rises in HDL cholesterol and apolipoprotein A-1 than did rosuvastatin monotherapy. Rosuvastatin monotherapy was better tolerated than ER niacin taken either alone or with rosuvastatin. In this study, rosuvastatin very effectively improved the three major lipoprotein-lipid abnormalities of combined hyperlipidemia