A Case-Control Study of the Lymphatic Phenotype of Yellow Nail Syndrome.

BACKGROUND: Yellow nail syndrome (YNS) is a rare disease manifesting as a triad of yellow-green dystrophic nails, lymphedema, and chronic respiratory disease. The etiology of YNS is obscure and investigations are few. A single lymphatic pathogenesis has been proposed to account for all the associated features, and despite the lack of evidence for a unifying lymphatic mechanism, this hypothesis prevails. The objective was to explore the lymphatic phenotype in YNS and to establish whether lymphatic dysfunction could be a major contributing factor to the disease process. METHODS AND RESULTS: Four-limb lymphoscintigraphy was performed on patients with YNS and on healthy, age-matched controls. All 17 patients had lower limb swelling, and 14 (82%) had upper limb swelling also, including 5 (29%) with hand involvement. None of the YNS lymph scans was completely normal. Combined qualitative and quantitative assessment showed that 67% of YNS scans were clearly abnormal compared with 36% of healthy control scans. Mean axillary and ilio-inguinal nodal tracer uptakes were 41%-44% lower in the YNS group than in the controls (p < 0.0001). CONCLUSIONS: YNS is a lymphatic phenotype because lymphatic insufficiency was found to exist in all patients and the insufficiency was widespread (upper and lower limbs), with a common mechanistic fault of poor transport. The origin of the lymphatic fault is unclear. In healthy individuals, lymphatic abnormalities may be relatively common in the fifth decade of life onward.

Prognostic impact of reduced tumor-free margin distance on long-term survival in FIGO stage IB/II vulvar squamous cell carcinoma.

OBJECTIVE: We aimed to identify the minimum tumor-free margin distance conferring long-term oncological safety in patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB/II vulvar squamous cell carcinoma (VSCC). METHODS: This was a retrospective cohort study in patients with stage IB/II VSCC treated at a single institution in Turin, Italy. The main aim was to identify the minimum tumor-free margin distance that confers oncological safety in early-stage VSCC. Patients were divided in groups according to tumor-free histological margin distance to compare survival outcomes. Overall survival (OS), disease-specific survival (DSS), and recurrence rate (RR) were estimated by the Kaplan-Meier method for the newly proposed and the currently recommended 8 mm margin cut-off. Log-rank test was used to compare survival between groups. RESULTS: One hundred and fourteen patients met the study criteria. Median age was 68 years and median follow-up was 80 months. The minimum margin distance that conferred long-term oncological safety was 5 mm. OS, DSS were significantly lower in the <5 mm group when compared with the ≥5 mm group (p=0.002 and p=0.033, respectively) although no difference in RR was observed between groups. Analysis at the 8-mm cut-off indicated there is no difference in OS, DSS, or RR between groups. CONCLUSION: FIGO stage IB/II VSCC patients' prognosis is affected by margin distance. Long-term survival is significantly reduced in patients with tumor-free margins <5 mm, even in the absence of lymph node metastasis. Thus, these patients should be offered further surgical or adjuvant treatment.

Constitutively Enhanced Lymphatic Pumping in the Upper Limbs of Women Who Later Develop Breast Cancer-Related Lymphedema.

BACKGROUND: It has previously been shown that the lymph drainage rate in both upper limbs is greater in women destined to develop breast cancer-related lymphedema (BCRL) than in those who do not develop BCRL, indicating a constitutive predisposition. We explored constitutive differences further by measuring the maximum lymphatic pump pressure (Ppump) and the rate of (99m)Tc-Nanocoll transport generated by the contractile upper limb lymphatics before and after breast cancer surgery in a group of women who were followed for 2 years to determine their eventual BCRL or non-BCRL status. METHODS AND RESULTS: Ppump and tracer transport rate were measured by lymphatic congestion lymphoscintigraphy in the ipsilateral upper limb in 26 women pre- and post-breast cancer surgery. BCRL occurred in 10/26 (38.5%) cases. Ppump in the women who later developed BCRL (40.0 ± 8.2 mmHg) was 1.7-fold higher than in those who did not develop BCRL (23.1 ± 10.8 mmHg, p = 0.001). Moreover, the rate of lymph tracer transport into the forearm was 2.2-fold greater in the women who later developed BCRL (p = 0.052). Surgery did not significantly reduce Ppump measured 21 weeks postsurgery, but impaired forearm tracer transport in pre-BCRL women by 58% (p = 0.047), although not in those who did not develop BCRL. CONCLUSIONS: Women destined to develop BCRL have higher pumping pressures and lymph transport, indicating harder-working lymphatics before cancer treatment. Axillary lymphatic damage from surgery appears to compromise lymph drainage in those women constitutively predisposed to higher lymphatic pressures and lymph transport.

Intersection of two signalling pathways: extracellular nucleotides regulate pollen germination and pollen tube growth via nitric oxide.

Plant and animal cells release or secrete ATP by various mechanisms, and this activity allows extracellular ATP to serve as a signalling molecule. Recent reports suggest that extracellular ATP induces plant responses ranging from increased cytosolic calcium to changes in auxin transport, xenobiotic resistance, pollen germination, and growth. Although calcium has been identified as a secondary messenger for the extracellular ATP signal, other parts of this signal transduction chain remain unknown. Increasing the extracellular concentration of ATPgammaS, a poorly-hydrolysable ATP analogue, inhibited both pollen germination and pollen tube elongation, while the addition of AMPS had no effect. Because pollen tube elongation is also sensitive to nitric oxide, this raised the possibility that a connection exists between the two pathways. Four approaches were used to test whether the germination and growth effects of extracellular ATPgammaS were transduced via nitric oxide. The results showed that increases in extracellular ATPgammaS induced increases in cellular nitric oxide, chemical agonists of the nitric oxide signalling pathway lowered the threshold of extracellular ATPgammaS that inhibits pollen germination, an antagonist of guanylate cyclase, which can inhibit some nitric oxide signalling pathways, blocked the ATPgammaS-induced inhibition of both pollen germination and pollen tube elongation, and the effects of applied ATPgammaS were blocked in nia1nia2 mutants, which have diminished NO production. The concurrence of these four data sets support the conclusion that the suppression of pollen germination and pollen tube elongation by extracellular nucleotides is mediated in part via the nitric oxide signalling pathway.