Real-World Treatment Patterns and Survival Outcomes for Patients with Non-Metastatic Non-Small-Cell Lung Cancer in Sweden: A Nationwide Registry Analysis from the I-O Optimise Initiative.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, with ~40-50% of patients diagnosed with non-metastatic disease (stages IA-IIIC). The treatment landscape is evolving rapidly as immunotherapies and targeted therapy are introduced in the non-metastatic setting, creating a need to assess patient outcomes prior to their introduction. This real-world study using Swedish National Lung Cancer Registry data examined outcomes (overall survival (OS) and time to next treatment or death (TTNTD)) and treatment patterns for adults diagnosed with non-metastatic NSCLC. Baseline characteristics and OS from diagnosis were described for all patients; OS, treatment patterns, and TTNTD from treatment start were described for the treatment subgroup (patients diagnosed from 2014 onwards), stratified by disease stage and initial treatment. OS and TTNTD were described using the Kaplan-Meier estimator. The overall population (2008-2019) included 17,433 patients; the treatment subgroup included 5147 patients. Median OS (interquartile range) overall ranged from 83.3 (31.6-165.3) months (stage I patients) to 10.4 (4.3-24.2) months (stage IIIB patients). Among the treatment subgroup, median OS and TTNTD were longest among patients receiving surgery versus other anticancer treatments. These findings provide a baseline upon which to evaluate the epidemiology of non-metastatic NSCLC as newer treatments are introduced.

VE/VCO2 slope threshold optimization for preoperative evaluation in lung cancer surgery: identifying true high- and low-risk groups.

Background: Cardiopulmonary exercise testing (CPET) enables measurement of the slope of the increase in minute ventilation in relation to carbon dioxide elimination during exercise (the VE/VCO2 slope). Several studies have shown that the VE/VCO2 slope is a strong marker for postoperative complications and mortality. However, current thresholds for adverse outcomes are generated from historical data in heart failure patients. Methods: This was a retrospective analysis of 158 patients with lung cancer who underwent lobectomy or pneumonectomy during 2008-2020. The main outcome was major pulmonary complications (MPC) or death ≤30 days of cancer surgery. Patients were first categorized using two different single threshold approaches; the traditional threshold of 35 and the highest Youden value from the receiver operating curve (ROC) analysis. Secondly, patients were categorized into three risk groups using two thresholds. These two thresholds were determined in an ROC analysis, where the VE/VCO2 slope values generating either a 90% sensitivity (lower threshold) or a 90% specificity (upper threshold) for the main outcome were chosen. The frequency of complications was compared using Chi2. The overall model quality was evaluated by an area under the curve (AUC) analysis. Positive predictive values (PPVs) and negative predictive values (NPVs) are presented. Results: The two thresholds, <30 (90% sensitivity) and >41 (90% specificity), created three risk groups: low risk (VE/VCO2 slope <30, n=44, 28%); intermediate risk (VE/VCO2 slope 30-41, n=95, 60%) and high risk (VE/VCO2 slope >41, n=19, 12%). The frequency of complications differed between groups: 5%, 16% and 47% (P<0.001). Using two thresholds compared to one threshold increased the overall model quality (reaching AUC 0.70, 95% confidence interval: 0.59-0.81), and identified a high sensitivity threshold (VE/VCO2 slope <30) which generated a NPV of 95% but importantly, also a high specificity threshold (VE/VCO2 slope >41) with a PPV of 47%. Conclusions: Risk stratification based on three risk groups from the preoperative VE/VCO2 slope increased the model quality, was more discriminative and generated better PPV and NPV compared to traditional risk stratification into two risk groups.

Ventilatory efficiency in combination with peak oxygen uptake improves risk stratification in patients undergoing lobectomy.

Objective: We aimed to evaluate whether or not using the slope of the increase in minute ventilation in relation to carbon dioxide (VE/VCo2-slope), with a cutoff value of 35, could improve risk stratification for major pulmonary complications or death following lobectomy in lung cancer patients at moderate risk (Vo2peak = 10-20 mL/kg/min). Methods: Single center, retrospective analysis of 146 patients with lung cancer who underwent lobectomy and preoperative cardiopulmonary exercise testing in 2008-2020. The main outcome was any major pulmonary complication or death within 30 days of surgery. Patients were categorized based on their preoperative cardiopulmonary exercise testing as: low-risk group, peak oxygen uptake >20 mL/kg/min; low-moderate risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope <35; and moderate-high risk, peak oxygen uptake 10 to 20 mL/kg/min and VE/VCo2-slope ≥35. The frequency of complications between groups was compared using χ2 test. Logistic regression was used to calculate the odds ratio with 95% CI for the main outcome based on the cardiopulmonary exercise testing group. Results: Overall, 25 patients (17%) experienced a major pulmonary complication or died (2 deaths). The frequency of complications differed between the cardiopulmonary exercise testing groups: 29%, 13%, and 8% in the moderate-high, low-moderate, and low-risk group, respectively (P = .023). Using the low-risk group as reference, the adjusted odds ratio for the low-moderate risk group was 3.44 (95% CI, 0.66-17.90), whereas the odds ratio for the moderate-high risk group was 8.87 (95% CI, 1.86-42.39). Conclusions: Using the VE/VCo2-slope with a cutoff value of 35 improved risk stratification for major pulmonary complications following lobectomy in lung cancer patients with moderate risk based on a peak oxygen uptake of 10 to 20 mL/kg/min. This suggests that the VE/VCo2-slope can be used for preoperative risk evaluation in lung cancer lobectomy.

A Well-Defined Endobronchial Tumor in a 26-Year-Old Man.

CASE PRESENTATION: A 26-year-old man presented with a 2-week history of productive cough and a 1-year history of effort-related dyspnea. His medical history was significant for hay fever and exertion-triggered asthma. He was not taking medicines regularly but was using inhaled salbutamol as needed. He was an ex-smoker, with a previous history of 2-pack years.

Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle.

In this paper, we investigated the isoform-specific roles of certain protein kinase C (PKC) isoforms in the regulation of skeletal muscle growth. Here, we provide the first intriguing functional evidence that nPKCδ (originally described as an inhibitor of proliferation in various cells types) is a key player in promoting both in vitro and in vivo skeletal muscle growth. Recombinant overexpression of a constitutively active nPKCδ in C2C12 myoblast increased proliferation and inhibited differentiation. Conversely, overexpression of kinase-negative mutant of nPKCδ (DN-nPKCδ) markedly inhibited cell growth. Moreover, overexpression of nPKCδ also stimulated in vivo tumour growth and induced malignant transformation in immunodeficient (SCID) mice whereas that of DN-nPKCδ suppressed tumour formation. The role of nPKCδ in the formation of rhabdomyosarcoma was also investigated where recombinant overexpression of nPKCδ in human rhabdomyosarcoma RD cells also increased cell proliferation and enhanced tumour formation in mouse xenografts. The other isoforms investigated (PKCα, ß, ε) exerted only minor (mostly growth-inhibitory) effects in skeletal muscle cells. Collectively, our data introduce nPKCδ as a novel growth-promoting molecule in skeletal muscles and invite further trials to exploit its therapeutic potential in the treatment of skeletal muscle malignancies.

Double unfurled dartos flap technique in the surgical treatment of recurrent urethrocutaneous fistulas.

BACKGROUND: The management of recurrent urethrocutaneous fistula (RUCF) is a challenging problem that poses a serious difficulty for the hypospadias surgeon. We report here a novel technique in which a double unfurled dartos subcutaneous flap is utilized in the treatment of patients with RUCF. METHODS: We retrospectively reviewed the records of all our patients who underwent surgical treatment of urethrocutaneous fistula with this new operative method after previously failed fistula repair. The main novelty of this technique is the use of two opposite medium thickness flaps, unfurled from the inner surface of the dartos fascia and spread over the fistula and each other so as to cover the urethral suture line completely, and fixed to the surrounding corporal tissue. RESULTS: Eight patients with 11 RUCFs (with localizations varying from subcoronal to penoscrotal fistula opening) underwent surgical correction with the new method. There had previously been at least 3 recurrences in 6 of these patients, and different closure techniques had been used. RUCF diameter was <4 mm in all patients. Surgery was performed at the earliest following a 6-month healing period since the last fistula repair attempt. All of the RUCFs were repaired successfully with the technique. After a follow-up of at least 6 months, none of the 8 patients had developed recurrence of the fistula, and there were no postoperative complications. CONCLUSION: The double unfurled dartos subcutaneous flap method appears to be a simple and appropriate procedure with which to repair recurrent mid-shaft and proximal urethral fistulas after failed hypospadias repair.

[The treatment of spontaneous pneumothorax--focusing on the use of videothoracoscopy]. / A spontán pneumothorax kezelése különös tekintettel a videothoracoscopiára.

AIMS: Videothoracoscopy plays a leading role in the management of spontaneous pneumothorax. This study evaluates various treatment strategies based on early results. PATIENTS AND METHODS: In a five-year period 243 (184 male, 59 female, mean age: 37.1 years) patients were treated with spontaneous pneumothorax in 302 cases. In case of partial ptx observation was used in 24 (8%) and aspiration in 6 (2%) patients. Chest drain was inserted in 241 (67.6%) cases. Indications for surgery were recurrence of disease, previous contralateral pneumothorax and failure of drainage. Videothoracoscopy was indicated in 71 (23.5%), Jakoscopy in 5 (1.7%), thoracotomy in 13 (4.3%) cases. The operation was completed with partial pleurectomy in 25, talcum or mechanical pleurodesis in 32 and 3 cases, respectively. RESULTS: Conservative treatment was successful in 24 (80%) of the 30 conservatively treated cases, while chest drainage succeeded in 204 (84.7%) of the 241 cases. Conversion was needed in 8 (11.3%) cases of the 71 VATS. The remaining 63 patients recovered. Thoracotomy and Jakoscopy were successful in all cases. The postoperative complication rate was 6.3% after VATS, and 7.7% after thoracotomy. Reoperation was performed because bleeding in one case after VATS and thoracotomy. In one case empyema, and in another patient pneumonia developed after VATS. Postoperative bleeding occurred in one case after thoracotomy. The mean hospitalization was 8.5 days after drainage, 9.1 days after VATS and 11.3 days after thoracotomy. The postoperative mortality rate was 1.3% (4 patients). CONCLUSIONS: In case of spontaneous pneumothorax the first choice of therapy is chest tube drainage. VATS is indicated in case of recurrence, failure of drainage and previous contralateral pneumothorax.

[Intrathoracic migration of Kirschner wires]. / Kirschner-drótok intrathoracalis vándorlása.

Orthopedic surgeons apply metallic pins to stabilize the clavicule and humerus on a daily basis. Migration of these pins into the thoracic cavity is rare. We present the case of an elderly female patient, whose right humeroscapular joint was fixed with Kirschner wires due to recurrent luxation. Six weeks later, a follow-up X-ray revealed that the pins have migrated into the right thoracic cavity, confirmed by a CT chest. Videothoracoscopic removal of the metallic pins was not possible because of dense adhesions. Right anterolateral thoracotomy was carried out, and after pneumolysis one pin was taken out from the 2nd lung segment. The other one, which was running along the cupola and entering the spinal cord, was also removed. There was no postoperative surgical complication. The authors review the literature of this rare complication and point out that pins migrating into the thoracic cavity should be removed to avoid life threatening complications.

[Surgical management of sternoclavicular joint infections]. / Sternoclavicularis ízület fertözésének sebészi kezelése.

AIMS: The pyogenic infection of the sternoclavicular joint is a rare disease. The treatment can be conservative (antibiotics) or surgical (exposure and drainage of the joint or its resection). The authors analyze the causative and predisposing factors, the symptoms, the diagnosis, the questions of the therapy and its efficiency. PATIENTS AND METHODS: In the 6 cases (5 male, 1 female, average age: 56.8 years) the cause of the disease were trauma or metastatic septic focus in 2-2 cases and intraarticular injection or preceding radiotherapy in 1-1 case. Predisposing diseases (diabetes mellitus, gout, chronic alcoholism, liver cirrhosis) could be proved in two cases. The most frequent symptoms were the swelling and erythema of the joint, fever, pain and limitation of motion. In all cases the CT scan proved the destruction of the joint. In one case after unsuccessful conservative therapy and in 1-1 case after debridement and drainage because of concomitant multiple septic focuses and mediastinitis resection of the sternoclavicular joint was applied in a later second step. In the other three patients primary resection of the joint was performed. RESULTS: Both the conservative and drainage managements were insufficient. On the other hand the radical joint resection caused complete recovery in all cases. No intra and postoperative complications were observed. On an average 28.2 months after the radical operation the functional results were excellent. CONCLUSIONS: Relying upon the results, radical resection is supposed to be the most effective method. Conservative treatment or drainage are recommended only for cases associated with severe complications. Resection is worthy performing after the recovery of the concomitant illnesses.

Complete resolution of the microscopic protonation equilibria of N-methyl-D-aspartic acid and related compounds.

Protonation equilibria of N-methyl-D-aspartate (NMDA, a specific glutamate receptor agonist) and its derivatives are characterized at the macroscopic and microscopic levels. (1)H NMR-pH and pH-potentiometric titrations were carried out to determine the macroconstants. Microconstants were obtained by appropriate combination of acidity and NMR parameters of the parent compound and its three synthetic derivatives. These derivatives were close models of the NMDA minor microspecies, allowing the calculation of all the 12 microconstants, the 8 microspecies concentrations and 3 site interactivity parameters. Reliability of the microconstants was assessed by three independent test methods. It was found that protonation of the secondary amino site decreases the beta- and alpha-carboxylate basicities almost exactly by one and two orders of magnitude, respectively, whereas protonation of one of the carboxylates lessens the basicity of the other one by a factor of 3. NMR-pH profiles, macro- and microscopic protonation schemes and species-specific distribution diagrams are presented.

[Balloon dilatation of cervical anastomosis stricture after subtotal resection of the esophagus]. / Szubtotális nyelócsó-resectio után kialakult nyaki anastomosisszukület endoszkópos tágítása és annak eredményei.

AIMS: The stricture of the anastomosis is one of the most common complications of the subtotal esophageal resections. The authors present indications, technics and results of the endoscopic dilatation. PATIENTS AND METHODS: In a 10 year period 26 patients (22 male, 4 female, mean age of 53.7 years) with stricture of anastomosis between the esophagus and the neo-esophagus after subtotal esophageal resection were dilated endoscopically 82 times. The indication of the resection was tumour in 23 (88.5%) cases, congenital atresia in 2 (7.7%) cases and corrosive disease in one (3.8%) case. In 7 (31.8%) cases the stricture developed after anastomosis leakage. The mean time between the operation and the dilatation was 7.8 months. The cause of the stricture was cancer recurrency in 4 (15.4%) cases. RESULTS: There were no complications related to the dilatation. The mean number of the dilatation was 3.2 (1-9). There was no significant difference between the number of dilatation in patients with or without previously anastomotic leakage. The success rate of the dilatation for benign strictures was 95.5%. In only one patient (4.5%) was needed operative intervention. In the 4 patients with tumour recurrency a stent was also implanted in the stenosis. CONCLUSIONS: The endoscopic dilatation for the treatment of the cervical anastomosis stricture after subtotal esophageal resection is a successful method with a low rate of complications. In cases of tumour recurrency a stent implantation is suggested.

[Endoscopic stapled esophago-diverticulostomy as a new alternative to open surgery in the treatment of Zenker's diverticulum: which operation?]. / Endoszkópos oesophago-diverticulosto- mia, mint újabb lehetoség a Zenker diverticulum nyitott mutéti kezelése mellett: melyik mutétet válasszuk?

AIMS: The authors analyse the indications, contraindications, early and late results of two types of operations (resection of the diverticulum with crycopharyngeal myotomy and endoscopic stapled esophago-diverticulostomy) for the treatment of Zenker's diverticulum. PATIENTS AND METHODS: In a five year period 10 patients (5 male, 5 female, mean age 56.9 years) were operated for Zenker's diverticulum. Six open and 4 endoscopic operations were planned, although in one case the placement of the endoscope was unsuccessful. Open surgery was planned if the diverticulum was in lateral position, if it was too small or large and if endoscopic surgery was technically impossible. RESULTS: The operative time was shorter in the endoscopic group (32.3 vs. 80.7 minutes). In the open surgery group (7 patients) one saliva fistula developed caused by suture leak. The length of hospital stay was 8.1 days in the resection group and 4.7 in the endoscopic group. No recurrence developed. CONCLUSIONS: The advantages of the endoscopic oesophago-diverticulostomy are: shorter operating time and hospital stay, less complication rate and it is minimally invasive. The authors suggest endoscopic oesophago-diverticulostomy as the choice of operation in case of Zenker's diverticulum. Open surgery is indicated only if the diverticulum is in lateral position or if it is bigger than 8 cms. The technical contraindications for endoscopic surgery are: short, rigid neck and limited mouth opening.

[Synthesis of dicarboxylic acid monoamides]. / Amidcsoport szelektív kialakítása dikarbonsavakban.

The pharmaceutical and biological importance of the amide moiety is briefly surveyed. Relationships between the electron density and chemical reactivity of the amide site are shortly described. Synthetic methods for the selective formation of monoamino-dicarboxylic acid alpha and beta monoamides are summarised. The three major selective synthesis routes for the preparation of monoamides are introduced. The first class of synthetic methods consists of non selective formation of a- and b-esters, followed by their separation on the basis of different solubilities. Amidation of these esters results in the alpha- or beta-amides respectively. The second class of the reactions utilises the orientating capacity of the amino (ammonium) site, producing first various cyclic anhydrides, lactames, lactones, which are then decomposed in hydrolytic, aminolytic, etc. reactions, resulting selectively in the alpha- or beta-amides or esters. Reactants in the third class of the reactions are dicarboxylic acids with carbon-carbon pi-bonds, and ammonia (or alkyl-amine) which form the appropriate compound in addition reactions. Reactivities and selectivities are interpreted in terms of inductive effects, acidity differences and electronic effects of the various protecting groups. Some important analytical properties of monoamino-dicarboxylic acids and their monoamides are compiled.

[Reconstruction of cervical esophageal anastomosis using median sternotomy]. / Nyaki nyelócsó anasztomózisok rekonstrukciója median sternotomia segítségével.

We performed cervical oesophageal anastomosis in 153 patients in 10 years. In 11 patients reconstruction or delayed anastomosis was performed through median sternotomy because cervical approach was not suitable. Reoperations were the following: 7 oesophageal stenosis which couldn't be dilated, 2 necrosis of the transplanted organ and 2 because of delayed anastomosis. 8 patients had oesophageal tumors and 3 erosive fluid reflux. During median sternotomy the transplanted organ was injured twice. In 9 patients after reconstruction dysphagia disappeared, in one pharyngo-ileostomy stenosis was noticed and one of the patients died because of ARDS after a leak.