Short duration of upper extremity lymphedema correlates with a favorable cytokine response after lymph node transfer surgery.

Vascularized lymph node transfer surgery (VLNT) can provide benefit to lymphedema patients. Cytokines may play a role in the development of lymphedema and in the regeneration of lymphatic vessels after VLNT. Our primary aim was to investigate whether the VLNT patients have a specific cytokine profile. Our secondary aim was to see whether the preoperative lymphedema or severity affects the postoperative cytokine response. Wound exudate was gathered from 18 patients undergoing VLNT on the first and sixth postoperative day (POD). The concentrations of IL-10, TNF-α, TGF-ß1 and VEGF-C were analyzed using enzymelinked immune-sorbent assays. A general score was generated to assess the benefit of the surgery. The changes in cytokine concentrations (1st POD-6th POD) were correlated with the pre- and postoperative lymphedema related factors. A shorter duration of lymphedema preoperatively correlated with an increase in the concentration of IL-10 and TNF-ß during the first six PODs (IL-10: r=0.495, p=0.051; TNF-α: r=0.737, p=0.006) and a decrease in the concentration of TGF-ß1 (r= -0.613, p=0.020). The increase of the concentration of TNF-α during the first six PODs also correlated with a greater total general score (r=0.775, p=0.005) and hence indicated a better response to the surgery. The patients with a shorter duration of lymphedema preoperatively had a more favorable cytokine response during the first six PODs after VLNT.

Everolimus-induced pneumonitis associates with favourable outcome in patients with metastatic renal cell carcinoma.

BACKGROUND: Mammalian target of rapamycin inhibitors may induce pneumonitis. We analysed the association of pneumonitis with outcomes in everolimus treated metastatic renal cell carcinoma (mRCC) patients. PATIENTS AND METHODS: Eighty-five mRCC patients received everolimus at Helsinki University Hospital (cohort A). Computed tomography (CT) verified pneumonitis was correlated with outcome using Kaplan-Meier, Cox regression and logistic regression. An independent cohort of 148 everolimus treated mRCC patients (cohort B) at Aarhus University Hospital was assessed for validation. RESULTS: In cohort A, CT-verified pneumonitis (N = 29, 34.1%) was associated with improved overall survival (OS) (24.7 versus 8.5 months; P < 0.001), progression-free survival (PFS) (5.5 versus 3.2 months; P = 0.002) and clinical benefit rate (CBR) 57.1% versus 24.1% (P = 0.003). In multivariate analyses pneumonitis was associated with improved OS (hazard ratio [HR], 0.22; 95% confidence interval [CI] 0.12-0.44; P < 0.001), PFS (HR 0.37; 95% CI 0.21-0.66; P = 0.001) and CBR (odds ratio [OR] 4.11; 95% CI 1.42-11.95; P = 0.01). In cohort B, CT-verified pneumonitis (N = 29, 19.6%) was associated with improved OS (12.9 versus 6.0 months; P = 0.02), PFS (6.0 versus 2.8 months; P = 0.02) and CBR (79.3% versus 39.5%; P < 0.001). In multivariate analyses pneumonitis was associated with improved OS (HR 0.58; 95% CI 0.36-0.94; P = 0.03), PFS (HR 0.61; 95% CI 0.39-0.95; P = 0.03) and CBR (OR 5.65; 95% CI 2.10-15.18; P = 0.001). In a combined multivariate analysis (N = 233), with pneumonitis as a time-dependent covariate, CT-verified pneumonitis was associated with longer OS (HR, 0.67; 95% CI 0.46-0.97; P = 0.03). Furthermore, in a landmark analysis, pneumonitis was associated with longer OS (17.4 versus 7.8 months; P = 0.01). CONCLUSIONS: Everolimus-induced pneumonitis is associated with improved outcome in patients with mRCC and may serve as a biomarker of everolimus efficacy.

Endoscopic Nd:YAG laser palliation of malignant duodenal tumors.

This study assesses the outcome of 20 patients referred for neodymium: yttrium-aluminum-garnet laser therapy of malignant duodenal tumors between 1984 and 1992. Almost all (95%) of these patients required palliative therapy for gastrointestinal hemorrhage, and nearly half (45%) also had obstructive symptoms. A mean of 3 (range, 1 to 6) laser treatment sessions were required for palliation. Laser therapy eliminated the need for blood transfusions in only 38% of patients. Obstructive symptoms were improved in all patients after laser treatment. Treatment failure could not be predicted on the basis of demographic factors (other than age), tumor characteristics, or transfusion requirements. Survival after laser therapy was 30% at 6 months and 15% at 12 months. Endoscopic neodymium:yttrium-aluminum-garnet laser therapy is a reasonable approach for palliation of malignant tumor obstruction or hemorrhage in selected cases; however, hemorrhage often continues.

Apoptosis occurs in lymphoma cells but not in hepatoma cells following ionizing radiation and photodynamic therapy.

The aim of this study was to determine the relative role of apoptosis in photodynamically-induced cytotoxicity or radiation-induced cytotoxicity for hepatoma and lymphoma cells. Human hepatoma cells and mouse lymphoma cells were treated with either photodynamic therapy (PDT) or ionizing radiation. Dosimetry studies of immediate cell death following photodynamic therapy in the hepatoma cell line demonstrated second-order kinetics, similar to that seen in the lymphoma cells. No immediate cell death was noted in the hepatoma or lymphoma cells following ionizing radiation, but experiments measuring delayed cell death demonstrated a dose-dependent response. Maximum DNA ladder formation occurred 2 hr after PDT and 24 hr after ionizing radiation in the lymphoma cells, which was consistent with the time courses of cell death for these treatments. The hepatoma cell line did not demonstrate DNA ladder formation despite dosages of PDT or ionizing radiation sufficient to cause high levels of cytotoxicity.

Gastroesophageal reflux and chronic cough: which comes first?

We evaluated the relationship between gastroesophageal (GE) reflux and chronic cough using prolonged pH monitoring and the standard acid reflux study in a retrospective case review. Ten patients were referred to our clinical esophageal laboratory for prolonged pH monitoring to determine whether GE reflux was the cause of chronic cough. In addition, we report one patient referred for a standard acid reflux test as a clear example of spontaneous cough inducing GE reflux. Of the 10 patients having prolonged pH monitoring, 182 of 221 (80.9 +/- 4.6%) of cough episodes had no correlation with GE reflux (p = 0.0001). Of those cough episodes that appeared to be related to GE reflux, 27 of 39 (69.2 +/- 11.7%) occurred before GE reflux and 12/39 (30.8 +/- 10.3%) occurred after GE reflux (p = 0.06). In the single patient GE reflux after spontaneous cough occurred five of seven times during a standard acid reflux test. In our series, cough and reflux were not related in the majority of episodes. Where there was a relationship, it appeared that the cough preceded GE reflux twice as often as reflux preceded cough. We conclude that GE reflux does not appear to be a frequent cause of chronic cough.