Primary spontaneous pneumothorax in younger patients with their first episode had a much higher recurrence rate than previously reported. Every doctor who treats patients with primary spontaneous pneumothorax should be aware and patients informed.

ClinicalTrial.gov: NCT 02866305.

Background: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome, characterised by familial aggregation of HNPCC related cancers, germline mutations in mismatch repair genes, and/or microsatellite instability (MSI) in tumour tissue. Aim: To estimate the frequency of HNPCC among non-selected Danish patients with colorectal cancer (CRC), and to evaluate the value of MSI analysis as a pre-screen test.Methods: This was a prospective population based study on consecutive CRC patients. A family history of malignancy was obtained and suspected HNPCC cases were screened for hMLH1/hMSH2 mutations and subjected to MSI analysis. Patients with germline mutations and/or those with Amsterdam criteria I or II families were categorised as HNPCC patients. Results: Among 1328 eligible CRC patients, 1200 (90.4%) completed a questionnaire. A total of 1.7% (95% confidence interval (CI) 1.0-2.4) (20 cases) were categorised as HNPCC patients. Amsterdam criteria I or II were met in 18 cases (1.5%), and in another two cases (0.2%) pathogenic hMLH1/ hMSH2 mutations were detected without fulfilment of the Amsterdam criteria I or II. Among 77 patients younger than 50 years of age, 11 cases (14.3%) were categorised as HNPCC. The Amsterdam criteria I or II were met in eight of 10 gene carriers (80%). The MSI-high phenotype was demonstrated in all 10 gene carriers. Conclusion: The frequency of HNPCC was approximately 1.7% among all CRC cases and 14.3% among patients younger than 50 years of age. MSI analysis is a reliable pre-screen test for hMLH1/ hMSH2 mutations in families suspected of having HNPCC.

Key pointsr Initial studies have described the electrical properties of lymphatic smooth muscle cells from different animal species and the ion channels contributing to these properties. However, there is a translational gap to the human situation where studies on human tissue are lacking.r Voltage-gated sodium channels are essential for the generation of action potentials, and thus spontaneous contractions in human lymphatic vessels, but not noradrenaline-induced contractions. A sodium channel opener elicited contractions as a result of calcium influx via voltage-gated calcium channels and the sodium-calcium exchanger.r Pharmacological characterization and the mRNA expression profile indicate that Na v 1.3 is the most prevalent sodium channel.r These results provide support for an important role of sodium channels in spontaneous human lymphatic vessel electrical activity and contractility.Abstract Voltage-gated sodium channels (VGSC) play a key role for initiating action potentials (AP) in excitable cells. VGSC in human lymphatic vessels have not been investigated. In the present study, we report the electrical activity and APs of small human lymphatic collecting vessels, as well as mRNA expression and function of VGSC in small and large human lymphatic vessels. The VGSC blocker TTX inhibited spontaneous contractions in six of 10 spontaneously active vessels, whereas ranolazine, which has a narrower VGSC blocking profile, had no influence on spontaneous activity. TTX did not affect noradrenaline-induced contractions. The VGSC opener veratridine induced contractions in a concentration-dependent manner (0.1-30 μM) eliciting a stable tonic contraction and membrane depolarization to −18 ± 0.6 mV. Veratridine-induced depolarizations and contractions were reversed ß80% by TTX, and were dependent on Ca 2+ influx via L-type calcium channels and the sodium-calcium exchanger in reverse mode. Molecular analysis determined Na V 1.3 to be the predominantly expressed VGSC isoform. Electrophysiology of mesenteric lymphatics determined the resting membrane potential to be −45 ± 1.7 mV. Spontaneous APs were preceded by a slow depolarization of 5.3 ± 0.6 mV after which a spike was elicited that almost completely repolarized before immediately depolarizing again to plateau. Vessels transiently hyperpolarized prior to returning to the resting membrane potential. TTX application blocked APs. We have shown that VGSC are necessary for initiating and maintaining APs and spontaneous contractions in human lymphatic vessels and our data suggest the main contribution from comes Na V 1.3. We have also shown that activation of these channels augments the contractile activity of the vessels.

BACKGROUNDGermline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high sensitivity and identify all mutated cases without too many false‐positive cases.METHODSSequencing was compared with microsatellite analysis and immunohistochemistry to detect the presence or absence of the mismatch repair proteins. In the current study, the authors examined 42 patients with colorectal carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty‐five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced.RESULTSNinety‐two percent of patients with germ line mutations were detected by either immunohistochemistry or microsatellite instability, indicating that a combination of these methods may be suitable for HNPCC screening. Microsatellite instability and abnormal immunohistochemical staining were found in 73% of the tumors. Concordance among the three methods was found in 74 % of the tumors.CONCLUSIONSThe authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated. Cancer 2002;95:2422–30. © 2002 American Cancer Society.DOI 10.1002/cncr.10979