Complication rates rise with age and Haller index in minimally invasive correction of pectus excavatum: A high-volume, single-center retrospective cohort study.

OBJECTIVES: The study objectives were to describe the compounded complication rate of minimally invasive repair of pectus excavatum, identify predisposing risk factors, and evaluate the optimal timing of correction. Minimally invasive repair of pectus excavatum is the standard treatment for pectus excavatum and consists of 2 invasive procedures, for example, correction with bar insertion followed by bar removal after 2 to 3 years. METHODS: A retrospective cohort study identifying children, adolescents, and adults of both genders corrected for pectus excavatum with minimally invasive repair of pectus excavatum between 2001 and 2022. Information on complications related to bar insertion and removal procedures for each individual patient was compiled into a compounded complication rate. Complication severities were categorized according to the Clavien-Dindo classification. RESULTS: A total of 2013 patients were corrected by minimally invasive repair of pectus excavatum with a median age (interquartile range) for correction of 16.6 (5) years. Overall compounded complication rate occurred at a frequency of 16.4%, of which 9.3% required invasive reinterventions (Clavien-Dindo classification ≥IIIa). The complication rate related to bar insertion was 2.6-fold higher compared with bar removal (11.8% vs 4.5%, respectively). Multivariable analysis revealed age (adjusted odds ratio, 1.05; P < .001), precorrection Haller Index (adjusted odds ratio, 1.10; P < .033), and early-phase institutional experience (adjusted odds ratio, 1.59; P < .002) as independent predisposing risk factors. The optimal age of correction was 12 years, and the compounded complication rate correlated exponentially with age with a doubling time of 7.2 years. Complications increased 2.2-fold when the Haller index increased to 5 or more units. CONCLUSIONS: Minimally invasive repair of pectus excavatum is associated with a high compounded complication rate that increases exponentially with age and high Haller Index. Consequently, we recommend repair during late childhood and early adolescence, and emphasize the importance of informing patients and relatives about the significant risks of adult correction as well as the need of 2 consecutive procedures taking the complication profile into account before planning surgery.

Safe and efficient 2-step implementation of totally minimally invasive esophagectomy.

Background: The clinical benefits of totally minimal invasive esophagectomy (TIME) compared to open esophagectomy are documented and include reduced morbidity like pulmonary infections, shorter hospital stay and an increase in short-term quality of life. However, transition to TIME can be associated with a learning curve associated increased morbidity. We report our implementation of TIME using a 2-step approach, where the thoracoscopic part was added to the laparoscopic part in carefully selected patients. The hypothesis was that the 2-step implementation provides a safe and efficient implementation without compromising the outcomes for the patients. The aim of this study was to evaluation the implementation of minimal invasive esophagectomy at Aarhus University Hospital, where a 2-step implementation strategy has been used. Methods: In this retrospective observational cohort study a total of 369 patients with esophagus or gastroesophageal cancers underwent esophagectomy from September 1st, 2016 to July 31st, 2021 in a single high-volume tertiary institution. Totally minimally invasive Ivor Lewis esophagectomy was performed by experienced minimal invasive surgeons in 120 of the cases. The study presents the complication rates of the TIME patients in the implementation phase. Results: Anastomotic leakage occurred in 7.5% of the cases and pneumonia occurred in 5.8% of the cases. The lymph node count reached 16 or more in 94.3% of the cases and R0-resection was performed in 98.3% of the cases. Textbook outcome for esophageal cancer surgery was achieved in 45.8% of the patients. Conclusions: Hybrid minimal invasive esophagectomy can serve as a step towards totally minimally invasive esophagectomy. In our institution, major learning curve associated complications was avoided and a high level of cancer control was achieved by a 2-step implementation strategy in carefully selected patients.

Individualised perioperative blood pressure and fluid therapy in oesophagectomy ­ study protocol for a randomised clinical trial

INTRODUCTION: Oesophagectomy is the mainstay of curative treatment for oesophageal cancer, but it is associated with a high risk of major complications. Goal-directed fluid therapy and individualised blood pressure management may prevent complications after surgery. Extending goal-directed fluid therapy after surgery and applying an individual blood pressure target may have substantial benefit in oesophagectomy. This is a protocol for a clinical trial implementing a novel haemodynamic protocol from the start of anaesthesia to the next day with the patient's own night-time blood pressure as the lower threshold. METHODS: This is a single-centre, single-blind, randomised, clinical trial. Oesophagectomy patients are randomised 1:1 for either perioperative haemodynamic management according to a goal-directed fluid therapy protocol with an individual target blood pressure or for standard care. The primary endpoint is the total burden of morbidity and mortality assessed by the Comprehensive Complication Index 30 days after surgery. Secondary endpoints are complications, reoperations, fluid and vasopressor dosage and quality of life at 90 days after surgery. CONCLUSIONS: The results from this trial provide an objective and easy-to-follow algorithm for fluid administration, which may improve patient-centred outcomes in oesophagectomy patients. FUNDING: The trial is supported by Aarhus University (1,293,400 DKK) and the Novo Nordisk Foundation (625,200 DKK). TRIAL REGISTRATION: EudraCT number: 2021-002816-30.

Oncological results and morbidity following intended curative resection and free jejunal graft reconstruction of cervical esophageal cancer: a retrospective Danish consecutive cohort study.

BACKGROUND: The role of surgery in treatment of locally advanced cervical esophageal cancer (CEC) remains debated. In the European and American treatment guidelines, definitive chemoradiotherapy (dCRT) is preferred over surgery, while in the Danish guidelines, the two treatment modalities are equally recommended. Surgical treatment of CEC is centralized at our center in Denmark. We present our outcomes following neoadjuvant chemoradiotherapy (nCRT) when possible and resection as first-line therapy for CEC and compare with recent published dCRT results. METHOD: We retrospectively reviewed the medical charts of patients treated for cervical esophageal cancer at Aarhus University Hospital from 2001-2018 with nCRT when possible and pharyngolaryngectomy followed by reconstruction with a free jejunal graft. RESULTS: Forty consecutive patients were included. About, 45% received nCRT. The median survival was 21 months. The overall, disease-specific and disease-free 5-year survival was 43.6%, 53.2%, and 47.4%, respectively. The rate of microscopically radical resection was 85%. The recurrence rate was 47% and 81% of recurrences were locoregional. The in-hospital and 30-day mortality rate was 0%. Major complications occurred in 27.9%. Anastomotic leakage, graft failure, fistulas and strictures occurred in 10%, 7.5%, 30%, and 30%, respectively. CONCLUSION: Our treatment offers equal oncological results compared to the best internationally published results for dCRT for CEC. Results vary considerably between dCRT studies. Morbidity appears more pronounced following surgery. Future studies are warranted to investigate the Danish national outcomes following dCRT as first-line treatment for curable locally advanced CEC.

Incidence and severity of surgical complications after pectus excavatum bar removal.

OBJECTIVES: Pectus bar removal is the final step of minimally invasive repair of pectus excavatum. Complication rates related to bar removal have been reported in 2-15% of patients and severe, near-fatal and fatal complications have been reported. No systematic assessment of complication severity or risk factors associated with bar removal has been reported in large study populations. The aim of this paper is to investigate the safety of the bar removal procedure with regard to complication rates and severities as well as assessment of risk factors. METHODS: Between 2003 and 2019, 1574 patients underwent the bar removal procedure. Medical records were assessed retrospectively and complications registered. Complications were categorized in infections, bleedings and other complications. The severity of the surgical complications was systematically classified using the validated Clavien-Dindo classification. Furthermore, risk factors associated with complications were assessed. RESULTS: The overall complication rate was 4.1% (Clavien-Dindo classification I-IV), mainly consisting of bleedings (1.3%) and infections (1.5%). Five cases of severe bleedings were registered (0.3%, Clavien-Dindo classification IV). Risk factors associated with complications during bar removal were greater age and removal of more than one bar. CONCLUSIONS: The bar removal procedure is a safe and effective procedure. Both age and number of bars inserted should be considered prior to surgical correction of pectus excavatum as these factors predict complications related to bar removal.

Prevalence of comorbidities in a surgical pectus excavatum population.

BACKGROUND: Pectus excavatum is the most common chest wall deformity and is associated to various connective tissue, cardiopulmonary, and skeletal abnormalities. Several conditions and syndromes have been associated to pectus excavatum, although the overall health implications of the pectus excavatum phenotype are unclear. Therefore, in this study we aimed to examine the health implications of the pectus excavatum phenotype by assessing all comorbidities and previous medical conditions in a cohort of patients undergoing pectus excavatum surgery. METHODS: This single-centre retrospective prevalence study included 1,046 patients undergoing minimal invasive repair of pectus excavatum from 2001 to 2012. Hospital medical charts were assessed and comorbidities and previous medical conditions were registered systematically and categorized according to the affected organ system. RESULTS: In our study population of 1,046 patients, we registered 623 conditions. The median age was 17 years and the majority of patients (56%) had no previous or present conditions. Notable prevalence of asthma (8.8%), allergies (12.3%), previous hernia surgery (5.2%), and psychiatric conditions (4.9%) were found. CONCLUSIONS: The majority of patients undergoing pectus excavatum surgery have no comorbidities or previous medical conditions. It seems that this patient category is comparable to the background population in this regard and our findings do not support screening this patient category for associated conditions.

Outcome and negative events in thoracic disc herniation surgery: a Danish registry study.

BACKGROUND: Thoracic disc herniation (TDH) is a surgically demanding entity. Various surgical approaches have been developed and advanced in an attempt to achieve sufficient outcomes and reduce consecutive complication rates. Still, controversy exists regarding selecting the best surgical approach. This retrospective study aims to support decision-making regarding surgical approach. METHODS: We performed a retrospective analysis of 71 patients who underwent thoracic discectomy at Aarhus University Hospital, Denmark, between 1996 and 2015. Patients were divided into two groups depending on whether a lateral approach or a posterior approach was used. Data on demographics, symptomatology, peri- and post-operative events, length of hospitalization and discharge disposition were assembled from medical records. RESULTS: Lateral and posterior approach had an approximately equal peri-operative event rate (39% versus 36%), whereas the lateral approach was associated with a higher post-operative event rate in-hospital and post-discharge than the posterior approach (50% versus 18%; 45% versus 40%). The overall probability of improvement in clinical outcome regardless approach at follow-up was 77% in the short-term and 80% in the long-term. Odds of clinical improvement at any time point was 29% higher with the lateral approach than with the posterior approach (OR = 1.29, 95% CI: 0.52-3.21, p = .76). Adjusting for time, the odds of clinical improvement at short-term follow-up was twice as high for the lateral than for the posterior approach (OR = 2.16, 95% CI: 0.16-30.11); however, the trend seems to fade away over time (OR = 1.10, 95% CI: 0.07-17.55). CONCLUSIONS: The probability of improving after TDH surgery is good. However, a clear conclusion regarding the best surgical approach cannot be established; thus, surgeons should consider pros and cons of each approach when allocating a patient to surgery.

Surgical correction of pectus carinatum.

Pectus carinatum is a common chest wall anomaly. It occurs five times more frequently in males than females and can be present at birth, although it usually progresses during adolescence. The correction of chest wall anomalies offers patients significant improvements in quality of life and it should never be regarded as an entirely cosmetic issue.  Most patients with pectus carinatum can be corrected with a brace. When bracing is not an option, good results can be obtained by surgery using the Ravitch method. In this method a midline incision is made over the sternum and costal cartilage is resected. In some patients the sternum protrudes and an osteotomy is necessary for optimal correction.

[Medical thoracoscopy in the elucidationof recurrent pleural effusion].

Medical thoracoscopy allows the respiratory physician access to inspection and biopsy of the pleura. The method has several names, such as pleuroscopy, non-intubated thoracoscopy and exploratory thoracoscopy, all of which cover the same procedure. The main indication for medical thoracoscopy is the diagnosis of recurrent pleural effusion, where pleural biopsy is needed. Medical thoracoscopy differs from thoracic surgical surgery as patients are sedated rather than in general anaesthesia. This is a review of the state of the art of pulmonological investigations of recurrent pleural effusion and the important role of medical thoracoscopy.

Spontaneous and α-adrenoceptor-induced contractility in human collecting lymphatic vessels require chloride.

Human lymphatic vessels are myogenically active and respond to sympathetic stimulation. The role of various cations in this behavior has recently been investigated, but whether the anion Cl- is essential is unclear. With ethical approval and informed consent, human thoracic duct and mesenteric lymphatic vessels were obtained from surgical patients. Spontaneous or norepinephrine-induced isometric force production from isolated vessels was measured by wire myography; the transmembrane Cl- gradient and Cl- channels were investigated by substitution of extracellular Cl- with the impermeant anion aspartate and inhibition of Cl- transport and channels with the clinical diuretics furosemide and bendroflumethiazide as well as DIDS and 5-nitro-2-(3-phenylpropylamino)benzoic acid. The molecular expression of Ca2+-activated Cl- channels was investigated by RT-PCR, and proteins were localized using immunoreactivity. Spontaneous and norepinephrine-induced contractility in human lymphatic vessels was highly abrogated after Cl- substitution with aspartate. About 100-300 µM DIDS or 5-nitro-2-(3-phenylpropylamino)benzoic acid inhibited spontaneous contractile behavior. Norepinephrine-stimulated tone was furthermore markedly abrogated by 200 µM DIDS. Furosemide lowered only spontaneous constrictions, whereas bendroflumethiazide had nonspecific inhibitory effects. Consistent expression of transmembrane member 16A [TMEM16A (anoctamin-1)] was found in both the thoracic duct and mesenteric lymphatic vessels, and immunoreactivity with different antibodies localized TMEM16A to lymphatic smooth muscle cells and interstitial cells. The significant change in contractile function observed with inhibitors and anion substitution suggests that Cl- movement over the plasma membrane of lymphatic myocytes is integral for spontaneous and α-adrenoceptor-evoked contractility in human collecting lymphatic vessels. Consistent detection and localization of TMEM16A to myocytes suggests that this channel could play a major functional role. NEW & NOTEWORTHY In this study, we report the first observations of Cl- being a critical ionic component of spontaneous and agonist-evoked contractility in human lymphatics. The most consistently expressed Ca2+-activated Cl- channel gene in the human thoracic duct and mesenteric lymphatic vessels appears to be transmembrane member 16A, suggesting that this channel plays a major role.

Surgical treatment versus conventional chest tube drainage in primary spontaneous pneumothorax: a randomized controlled trial.

OBJECTIVES: Primary spontaneous pneumothorax frequently recurs after chest tube management. Evidence is lacking whether patients may benefit from surgery following their first episode. METHODS: We performed a multicentre, randomized trial and enrolled young, otherwise healthy patients admitted with their first episode of primary spontaneous pneumothorax and treated using conventional chest tube drainage. Patients underwent high-resolution computed tomography on fully expanded lungs, and using web-based randomization, we assigned patients to continued conservative chest tube treatment or chest tube treatment followed by video-assisted thoracoscopic surgery (VATS) with the resection of bullae/blebs and mechanical pleurodesis. Patients were stratified into 2 groups based on the presence of bullae ≥1 cm on high-resolution computed tomography. The primary end point was readmission with ipsilateral recurrence. Secondary end points were complications and length of hospitalization. RESULTS: Between 1 August 2009 and 4 November 2016, we screened 457 patients, of whom 373 were eligible for inclusion and 181 were enrolled: male/female ratio = 5.0. We identified 88 patients with blebs <1 cm: 50 were randomly assigned to chest tube treatment and 38 to VATS. Ninety-three patients had bullae ≥1 cm: 43 were randomly assigned to chest tube treatment and 50 to VATS. Forty-three (23.8%) patients experienced recurrence during the follow-up period. Overall, recurrence was significantly lower following VATS when compared with conventional chest tube treatment (P = 0.0012). When stratified by bullae size, VATS proved significantly better for bullae ≥1 cm (P = 0.014). We observed a size-response relationship with increased risk of recurrence for larger bullae (P = 0.013). CONCLUSIONS: Surgery was an effective treatment to prevent recurrence in patients with their first presentation of primary spontaneous pneumothorax and should be the standard of care when high-resolution computed tomography demonstrates bullae ≥2 cm. Clinical trial registration: ClinicalTrial.gov: NCT 02866305.

Cannabis increased the risk of primary spontaneous pneumothorax in tobacco smokers: a case-control study.

OBJECTIVES: Previous smaller case series suggested that cannabis smoking may cause spontaneous pneumothorax, but this finding remains controversial. We investigated the possible association between smoking tobacco and cannabis and the risk of having a primary spontaneous pneumothorax in a large, homogeneous cohort of young, healthy individuals. METHODS: In a case-control study, we prospectively investigated young (≤40 years) patients admitted in Western Denmark from 2009 to 2016 with their first episode of primary spontaneous pneumothorax. Baseline characteristics and smoking habits including both tobacco and cannabis were obtained from questionnaires presented on admittance. We compared our findings with those of a population-based control group matched by age, sex and geographical area. Calculated odds ratios were compared using the Fisher's exact test for small frequencies and the χ2 test or the Mann-Whitney test for larger frequencies. RESULTS: A total of 416 patients participated (male/female ratio = 3.9). We observed a significantly increased risk of primary spontaneous pneumothorax in daily smokers compared with female never smokers (odds ratio = 8.10, 95% confidence interval: 4.61-14.14, P < 0.001) and male never smokers (odds ratio = 4.85, 95% confidence interval: 3.23-7.19, P < 0.001). The combination of smoking both cannabis and tobacco in men increased the risk of spontaneous pneumothorax significantly (odds ratio = 8.74, 95% confidence interval: 4.30-19.51, P < 0.001). In contrast, the cannabis habits of female patients did not differ from those of the Danish population in general. CONCLUSIONS: Combined smoking of tobacco and cannabis significantly aggravates the risk of having a primary spontaneous pneumothorax in young men compared to both never smokers and daily smokers.

Recurrent Primary Spontaneous Pneumothorax is Common Following Chest Tube and Conservative Treatment.

INTRODUCTION: Previous studies on primary spontaneous pneumothorax reported variable recurrence rates, but they were based on heterogeneous patient populations including secondary pneumothorax. We investigated young patients with primary spontaneous pneumothorax exclusively and used a national registry to track readmissions and calculate independent predictors of recurrence. METHODS: A prospective cohort study of consecutive young patients who were admitted over a 5-year period with their first episode of primary spontaneous pneumothorax and treated conservatively with a chest tube. Baseline characteristics were obtained from questionnaires presented on admittance. All patients were discharged with fully expanded lungs on chest radiography. Patient charts were identified in the national electronic patient registry for detailed information on readmissions due to recurrent spontaneous pneumothorax. RESULTS: We included 234 patients. Male/female = ratio 5/1. After a median observation period of 3.6 years (range 1-6 years), recurrent pneumothorax was observed in 54 %. Ipsilateral recurrence was the most common (79 %) but 30 % also experienced contralateral pneumothorax during the study period. Females had a significantly higher age at debut (p < 0.01) and experienced significantly more recurrences over time (p < 0.01). Low body weight (<60 kg) was an independent predictor of recurrence and patients with repeated recurrences were significantly younger at debut (p = 0.01). CONCLUSIONS: 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.

A Novel Device for Accurate Chest Tube Insertion: A Randomized Controlled Trial.

BACKGROUND: Optimal positioning of a large-bore chest tube is in the part of the pleural cavity that needs drainage. It is recommended that the chest tube be positioned apically in pneumothorax and basally for fluids. However, targeted chest tube positioning to a specific part of the pleural cavity can be a challenge. METHODS: A new medical device, the KatGuide, was developed for accurate guiding of a chest tube (28F) to an intended part of the pleural cavity. The primary end point of this randomized, controlled trial was optimal position of the chest tube. The optimal position in pneumothorax was apical (above the aortic arch), and the optimal position in hemothorax, hydrothorax, chylothorax, or empyema was basal (2 cm above the diaphragm or lower). The patients were randomized for the KatGuide method or the conventional forceps method, and rates of optimal position were compared. RESULTS: A total of 109 patients were enrolled (KatGuide: n = 49; conventional: n = 60). Chest tubes were optimally position in 41 (84%) in the KatGuide group vs 32 (53%) in the conventional group (p = 0.001). Experienced operators (>50 previous chest tube insertions) inserted 39 of the chest tubes, of which, 15 of 17 (88%) were optimally positioned in the KatGuide group vs 11 of 22 (50%) in the conventional group (p = 0.02). Two chest tubes (4%) were misplaced in the KatGuide group vs 11 (18%) in the conventional group (p = 0.04). No adverse device effects were observed. CONCLUSIONS: The KatGuide significantly improves the probability of optimal chest tube position and reduces the risk of misplacement compared with the conventional method. ClinicalTrial.gov Trial Registration Number: NCT01522885.

Familial colorectal cancer risk may be lower than previously thought: a Danish cohort study.

BACKGROUND: The risk of colorectal cancer (CRC) is reportedly increased two-fold if at least one first-degree relative (FDR) is affected with CRC, increasing to three- to four-fold if multiple FDRs are affected or if one FDR was diagnosed at a young age. We evaluated familial risk of CRC, systematically excluding monogenetic high-risk families with polyposis or Lynch syndrome/hereditary non-polyposis colorectal cancer (HNPCC). METHODS: FDRs of 1196 Danish CRC patients diagnosed between 1995 and 1998 (baseline) were identified and the family history of cancer was assessed at baseline using Danish medical registries; 4182 FDRs without CRC from 1060 of the families were matched on age and gender with ten individuals from the general population and followed from baseline to 2010. Family history was updated with any new cancer event during follow-up. RESULTS: Using Cox proportional hazard modeling the risk estimates were: at least one relative with CRC: hazard ratio (HR)=1.78 (95%CI: 1.45, 2.17), one relative with CRC diagnosed after the age of 50: HR=1.68 (95%CI: 1.32, 2.14), one relative with CRC diagnosed before the age of 50: HR=1.86 (95%CI: 0.70, 4.94), and multiple affected relatives: HR=2.04 (95%CI: 1.38, 3.00). CONCLUSION: Although the overall risk in FDRs of CRC patients in our study was comparable with the results of previous studies, the risk in families with multiple relatives with CRC or one CRC patient diagnosed young may be lower than reported previously.

Fixation of sternal fracture using absorbable plating system, three years follow-up.

Sternal fractures occur due to severe chest wall trauma in a small number of patients. They are often conservatively treated. The surgical intervention, although controversial, is indicated in case of deformity, severe pain, and ventilatory complications. We report the first case where absorbable plate has been used to fix a traumatic fracture in a 42-year-old female. After 3 years, the patient is still free of symptoms and CT scanning reveals intact sternal bone structure.

Survival in familial colorectal cancer: a Danish cohort study.

The monogenic Lynch syndrome (LS) is associated with better survival in colorectal cancer (CRC) patients. Whether family history of CRC affects CRC prognosis in general remains unclear. We evaluated overall mortality in a Danish cohort of CRC patients comparing patients with a family history (FHpos) to those without (FHneg) with focus on patients from non-syndromic families, thus FHpos patients were further divided into a non-syndromic group (FHNS) and a HNPCC/LS group (FHHNPCC). We included CRC patients diagnosed 1995-1998. First degree relatives were identified using Danish population registries and family history was obtained by linkage to Danish medical registries. 1- and 5-year mortality were evaluated using the Kaplan-Meier method and Cox regression, with adjustment for age, sex, cancer site, cancer stage, and comorbidity. 1196 CRC patients were included in the study, 219 FHpos patients of whom 197 were FHNS patients. 1- and 5-year adjusted Mortality Rate Ratios comparing FHpos patients to FHneg patients were 0.99 (95% CI 0.69, 1.42) and 1.07 (95% CI 0.87, 1.32), respectively. For FHNS patients, the corresponding MRRs were 1.01 (95% CI 0.69, 1.47) and 1.15 (95% CI 0.93, 1.43). For the FHHNPCC patients MRRs were 0.84 (95% CI 0.29, 2.44) and 0.66 (95% CI 0.33, 1.31), respectively. In contrast to the lower mortality in LS patients, other types of familial CRC do not seem to affect the survival after CRC diagnosis.

Voltage-gated sodium channels contribute to action potentials and spontaneous contractility in isolated human lymphatic vessels.

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 ∼80% 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 NaV 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 NaV 1.3. We have also shown that activation of these channels augments the contractile activity of the vessels.